A Study to Determine Safety, Tolerability and Pharmacokin... | NCT01677741 | Trialant
NCT01677741
Sponsor
Novartis Pharmaceuticals
Status
Completed
Last Update Posted
Nov 24, 2021Actual
Enrollment
85Actual
Phase
Phase 1Phase 2
Conditions
Neoplasms, Brain
Interventions
Dabrafenib
Countries
United States
Australia
Canada
Denmark
France
Germany
Israel
Italy
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT01677741
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
116013
Secondary IDs
ID
Type
Description
Link
2012-001499-12
EudraCT Number
CDRB436A2102
Other Identifier
Novartis
Brief Title
A Study to Determine Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib In Children and Adolescent Subjects
Official Title
Phase I/IIa, 2-Part, Multi-Center, Single-Arm, Open-Label Study to Determine the Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib in Children and Adolescent Subjects With Advanced BRAF V600-Mutation Positive Solid Tumors
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Oct 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 23, 2013Actual
Primary Completion Date
Dec 4, 2020Actual
Completion Date
Dec 4, 2020Actual
First Submitted Date
Aug 30, 2012
First Submission Date that Met QC Criteria
Aug 30, 2012
First Posted Date
Sep 3, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 3, 2021
Results First Submitted that Met QC Criteria
Oct 27, 2021
Results First Posted Date
Nov 24, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 27, 2021
Last Update Posted Date
Nov 24, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This was a 2-part, Phase I/IIa, multi-center, open label, study in pediatric and adolescent patients with advanced BRAF V600 mutation-positive solid tumors. Part 1 was a dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). Part 2 was an expansion study to further evaluate the safety, tolerability, and clinical activity of dabrafenib in 4 tumor-specific pediatric populations. Patients participated in only either part 1 or part 2 of the study.
Detailed Description
Part 1 was a dose escalation study in subjects with any BRAF V600 mutation-positive solid tumor, designed to optimize efficiency of enrollment, minimize the number of subjects being treated at potentially sub-efficacious dose levels, and incorporating the evolving pharmacokinetic, safety and efficacy data from the adult development program. Dose escalation part of the study was to determine the maximum tolerated dose (MTD) and recommend the dose for phase 2 studies (RP2D). An MTD has not been identified for dabrafenib in the adult population. This does not preclude the identification of an MTD in the pediatric population. Modified RSD was employed to determine the MTD. Part 1 used dual criteria of dose limiting toxicity (DLT) and observed dabrafenib exposures to make decisions to advance to the next dose level. Target exposure criteria based on adults treated at the approved adult dose of 300 mg (150 mg given BID) were observed in this study before meeting criteria for stopping dose escalation due to observations of DLTs, and served as the criteria for determining the RP2D for dabrafenib in pediatric subjects. Thus, MTD has not been established in pediatric population, similar to the previous dose finding efforts in adult subjects.
Part 2 was a tumor specific expansion study to further evaluate the safety/tolerability profile and to discover possible clinical efficacy of dabrafenib in 4 tumor-specific pediatric populations known to have BRAFV600 activation: high grade glioma (HGG), low grade glioma (LGG), Langerhans cell histiocytosis (LCH), miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other). The exposures for subjects dosed on the basis of weight were also evaluated by age categories.
Conditions Module
Conditions
Neoplasms, Brain
Keywords
Children and Adolescents
BRAF
dabrafenib
dose escalation
BRF116013
V600-mutation positive
BRF
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
85Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1: Dabrafenib treatment
Experimental
Three subjects will receive a single dose of 3 mg/kg dabrafenib on Day 1 and repeat dose will begin from Day 2, evenly divided in two daily doses. Once all 3 subjects have been fully evaluated for the first 28 days (including Day 15 PK) and no DLTs are observed, a next subject will be enrolled at the next higher dose levels (i.e., dose escalation to 3.75 mg/kg [+1] and may be further to 4.5 mg/kg [+2] and so on). If all 3 subjects have not been fully evaluated for the first 28 days or 1 DLT occurred, the fourth subject will be enrolled at the same dose level. If 2 or more DLTs are observed, the next subject will be enrolled at the next lower dose level (i.e., de-escalated to 2.25 mg/kg [-1] and may be further to 1.5 mg/kg [-2]). Similarly, the process is repeated for the fifth and sixth subjects in a cohort. All subjects will receive treatment till end of study.
Drug: Dabrafenib
Part 2: Cohort 1 Low-Grade Gliomas with BRAF V600 mutations
Experimental
Subjects with low-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
Drug: Dabrafenib
Part 2: Cohort 2 High-Grade Gliomas with BRAF V600 mutations
Experimental
Subjects with high-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
Drug: Dabrafenib
Part 2: Cohort 3 LCH with BRAF V600 mutations
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Dabrafenib
Drug
Dabrafenib is available as 50 mg or 75 mg capsules and as oral suspension (10 mg/mL for subjects unable to swallow capsules). Dabrafenib (either formulation) will be administered orally as a single dose on Day 1 and twice daily from Day 2, based on weight at the appropriate study dose level.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Incidence of Treatment Emergent Adverse Events (AEs) in Part 1 (Dose Escalation)
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Events, Serious Adverse Events and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.
From study treatment start date till 28 days safety follow-up, assessed up to approximately 90 months
Maximum Concentration (Cmax) of Dabrafenib
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax of dabrafenib was listed and summarized using descriptive statistics.
Week 1 Day 1, Week 3 Day 15
Area Under the Concentration-time Curve Over the Dosing Interval (AUC(0-τ)) and AUC From Zero to Infinity (AUC(0-inf)) of Dabrafenib
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUC(0-τ) and AUC(0-inf) of dabrafenib were to be listed and summarized using descriptive statistics.
Week 1 Day 1
Secondary Outcomes
Measure
Description
Time Frame
Pre-dose (Trough) Concentration (C Tau) of Dabrafenib and Its Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Pre-dose (trough) concentration (C tau) was to be listed and summarized using descriptive statistics for dabrafenib and its metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]).
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Written informed consent - a signed informed consent and/or assent (as age appropriate) will be obtained according to institutional guidelines.
Male or female >=12 months and <18 years of age at the time of signing the informed consent form.
Recurrent disease, refractory disease, or progressive disease after having received at least one standard therapy for their disease. Note: Subjects with metastatic (and surgically unresectable) melanoma can be enrolled for first-line treatment; Melanoma subjects with CNS involvement may be enrolled.
At least one evaluable lesion.
BRAF V600 mutation-positive tumor as confirmed in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory or equivalent (the local BRAF testing may be subject to subsequent verification by centralized testing; centralized testing can confirm V600E and V600K mutations only).
Performance score of >=50% according to the Karnofsky/Lansky performance status scale (subjects with a performance status of <=50% can be enrolled if the subject's confinement to bed and inability to carry out activities is due solely to cancer-related pain, as assessed by the investigator).
Females of child-bearing potential (with negative serum pregnancy test within 7 days prior to the first dose of study medication) must be willing to practice acceptable methods of birth control .
Sexually active males, who do not agree to abstinence, must be willing to use a condom during intercourse while taking the study drug, and for 16 weeks after stopping treatment and should not father a child in this period.
Must have adequate organ function as defined by the following values: Adequate bone marrow function defined as-absolute neutrophil count (ANC) >=1000/ microliter (µL), hemoglobin >=8.0 grams (g)/ deciliter (dL) (may receive red blood cell transfusions), platelets >=75,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment).
Adequate renal and metabolic function defined as: calculated glomerular filtration rate (eGFR) (Schwartz formula), or radioisotope GFR >=90 milliliters/minutes (mL/min)/1.73 meter square (m^2); or a serum creatinine within the institutional reference range upper limit of normal (for age/gender, if available).
Adequate liver function defined as: bilirubin (sum of conjugated + unconjugated) <=1.5 x upper limit of normal (ULN) for age, aspartate aminotransaminase (AST) and alanine transaminase (ALT) <=2.5 x ULN; AST/ALT may be <5 x ULN at baseline if disease under treatment involves the liver (requires radiographic confirmation of liver involvement).
Adequate cardiac function defined as: left ventricular ejection fraction (LVEF) of either >=50% by ECHO or greater than institutional lower limit of normal (LLN) by echocardiogram (ECHO) (while not receiving medications for cardiac function), corrected QT using Bazett's (QTcB) interval <450 milliseconds (msecs).
Exclusion Criteria:
Part 2 ONLY: Previous treatment with dabrafenib, another RAF inhibitor, or a mitogen-activated protein kinase (MEK) inhibitor (exception: prior treatment with sorafenib is permitted).
Malignancy OTHER than the BRAF mutant malignancy under study.
Had chemotherapy or radiotherapy within 3 weeks (or 6 weeks for nitrosoureas or mitomycin C) prior to administration of the first dose of study treatment.
The subject has received an investigational product within the following time period prior to the first dosing day in the current study: 28 days or 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is warranted by the data).
History of another malignancy. Exception: (a) Subjects who have been successfully treated and are disease-free for 3 years, (b) a history of completely resected non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission are eligible.
Current use of a prohibited medication or herbal preparation or requires any of these medications during the study.
Unresolved toxicity greater than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 Grade 2 or higher from previous anti-cancer therapy, including major surgery except those that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profile of dabrafenib (e.g., alopecia and/or peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy).
Has leukaemia.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib and its excipients.
Autologous or allogeneic stem cell transplant within 3 months prior to enrolment [NOTE: subjects with evidence of active graph versus host disease are excluded].
History of myocardial infarction, severe or unstable angina, peripheral vascular disease or familial QTc prolongation.
Subjects with abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (NOTE: subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study).
Subjects with moderate valvular thickening.
Known, uncontrolled cardiac arrhythmias (except sinus arrhythmia) within the past 24 weeks
Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease or uncontrolled infection), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.
Presence of active GI disease or other condition (e.g., small bowel or large bowel resection) that will interfere significantly with the absorption of drugs.
Hepatitis B Virus, or Hepatitis C Virus infection (subjects with laboratory evidence of Hepatitis B Virus clearance may be enrolled).
Pregnant females as determined by positive human chorionic gonadotropin (hCG) test at screening or prior to dosing.
Lactating females who are actively breast feeding.
Whitlock JA, Geoerger B, Dunkel IJ, Roughton M, Choi J, Osterloh L, Russo M, Hargrave D. Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis. Blood Adv. 2023 Aug 8;7(15):3806-3815. doi: 10.1182/bloodadvances.2022008414.
Hargrave DR, Bouffet E, Tabori U, Broniscer A, Cohen KJ, Hansford JR, Geoerger B, Hingorani P, Dunkel IJ, Russo MW, Tseng L, Dasgupta K, Gasal E, Whitlock JA, Kieran MW. Efficacy and Safety of Dabrafenib in Pediatric Patients with BRAF V600 Mutation-Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I/IIa Study. Clin Cancer Res. 2019 Dec 15;25(24):7303-7311. doi: 10.1158/1078-0432.CCR-19-2177.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
Patients participated in only either Part 1 (Dose Escalation) or Part 2 (Tumor specific expansion) of the study.
Recruitment Details
This study was conducted in 19 centers in eight participating countries: Australia (1), Canada (1), Denmark (1), Germany (1), France (4), Spain (1), United Kingdom (2), and United States (8).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
All subjects who received at least one dose of study treatment were included in All treated population and Safety population
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Aug 21, 2020
Jun 3, 2021
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Experimental
Subjects with LCH with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
Drug: Dabrafenib
Part 2: Cohort 4 Melanoma and PTC with BRAF V600 mutations
Experimental
Subjects with other tumors with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
Drug: Dabrafenib
Part 1: Dabrafenib treatment
Part 2: Cohort 1 Low-Grade Gliomas with BRAF V600 mutations
Part 2: Cohort 2 High-Grade Gliomas with BRAF V600 mutations
Part 2: Cohort 3 LCH with BRAF V600 mutations
Part 2: Cohort 4 Melanoma and PTC with BRAF V600 mutations
DRB436
Week 3 Day 15
The AUC(0-t) of Dabrafenib Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC[0-t]) dabrafenib metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]) were to be listed and summarized using descriptive statistics.
Week 1 Day 1, Week 3 Day 15
The AUC(0-tau) of Dabrafenib and Its Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-tau) of dabrafenib and its metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]) were to be listed and summarized using descriptive statistics.
Week 1 Day 1, Week 3 Day 15
Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F) of Dabrafenib
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. CL/F of dabrafenib was to be listed and summarized using descriptive statistics.
Week 1 Day 1, Week 3 Day 15
Maximum Concentration (Cmax) of Dabrafenib Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax of dabrafenib metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]) were listed and summarized using descriptive statistics.
Week 1 Day 1, Week 3 Day 15
Time to Reach Maximum (Peak) Plasma Concentration Following Drug Administration (Tmax) of Dabrafenib and Its Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was listed and summarized using descriptive statistics for dabrafenib and its metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]).
Week 1 Day 1, Week 3 Day 15
Elimination Half Life (T½) of Dabrafenib and Its Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. T1/2 of dabrafenib and its metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]) was listed and summarized using descriptive statistics.
Week 3 Day 15
Incidence of Treatment Emergent Adverse Events (AEs) in Part 2 (Tumor Specific Expansion)
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Events, Serious Adverse Event and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
From study treatment start date till 28 days safety follow-up, assessed up to approximately 90 months
Best Overall Response Based on Investigator Assessment Per Response Assessment in Neuro-Oncology (RANO) Criteria for Low Grade Glioma (LLG) Subjects
Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR).based on Response Assessment in Neuro-Oncology (RANO) criteria for Low Grade Glioma (LLG) and High Grade Glioma (HGG) subjects.
Up to 6 months
Best Overall Response Based on Investigator Assessment Per Response Assessment in Neuro-Oncology (RANO) Criteria for High Grade Glioma (HGG) Subjects
Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR).based on Response Assessment in Neuro-Oncology (RANO) criteria for Low Grade Glioma (LLG) and High Grade Glioma (HGG) subjects.
Up to 6 months
Effect of Weight on Total Apparent Clearance (CL/F) of Dabrafenib Estimated With a PopPK Model
The population pharmacokinetic (PopPK) model of Dabrafenib can be described using a two-compartment model with a delayed 1st order absorption (Alag1, Ka) and an inducible elimination (CL/F) that consists of a base clearance (constant over time, CL0/F) and a dose- and time-dependent inducible clearance (CLind/F). The PopPK analysis examined the influence of demographics (i.e., weight) on the pharmacokinetics of dabrafenib. The effect of weight on total apparent clearance (CL/F) of dabrafenib estimated with the PopPK model is summarized in this record.
Day 1-Predose, 0.5, 2 and 4 hours post dose; Day 15-Predose, 0, 0.5, 1, 2, 3, 4, 6 and 8 hours post dose.
Effect of Weight on Volume of Distribution (V/F) of Dabrafenib Estimated With a PopPK Model
The population pharmacokinetic (PopPK) model of Dabrafenib can be described using a two-compartment model with a delayed 1st order absorption (Alag1, Ka) and an inducible elimination (CL/F) that consists of a base clearance (constant over time, CL0/F) and a dose- and time-dependent inducible clearance (CLind/F). The PopPK analysis examined the influence of demographics (i.e., weight) on the pharmacokinetics of dabrafenib. The effect of weight on volume of distribution (V/F) of dabrafenib estimated with the PopPK model is summarized in this record.
Day 1-Predose, 0.5, 2 and 4 hours post dose; Day 15-Predose, 0, 0.5, 1, 2, 3, 4, 6 and 8 hours post dose.
Effect of Weight on Absorption Rate (ka) of Dabrafenib Estimated With a PopPK Model
The population pharmacokinetic (PopPK) model of Dabrafenib can be described using a two-compartment model with a delayed 1st order absorption (Alag1, Ka) and an inducible elimination (CL/F) that consists of a base clearance (constant over time, CL0/F) and a dose- and time-dependent inducible clearance (CLind/F). The PopPK analysis examined the influence of demographics (i.e., weight) on the pharmacokinetics of dabrafenib. The effect of weight on absorption rate (ka) of dabrafenib estimated with a PopPK model is summarized in this record.
Day 1-Predose, 0.5, 2 and 4 hours post dose; Day 15-Predose, 0, 0.5, 1, 2, 3, 4, 6 and 8 hours post dose.
Effect of Weight on Coefficients for Significant Covariates of Dabrafenib Estimated With a PopPK Model
The population pharmacokinetic (PopPK) model of Dabrafenib can be described using a two-compartment model with a delayed 1st order absorption (Alag1, Ka) and an inducible elimination (CL/F) that consists of a base clearance (constant over time, CL0/F) and a dose- and time-dependent inducible clearance (CLind/F). The PopPK analysis examined the influence of demographics (i.e., weight) on the pharmacokinetics of dabrafenib. The effect of weight on coefficients for significant covariates of dabrafenib estimated with a PopPK model is summarized in this record.
Day 1-Predose, 0.5, 2 and 4 hours post dose; Day 15-Predose, 0, 0.5, 1, 2, 3, 4, 6 and 8 hours post dose.
Kieran MW, Geoerger B, Dunkel IJ, Broniscer A, Hargrave D, Hingorani P, Aerts I, Bertozzi AI, Cohen KJ, Hummel TR, Shen V, Bouffet E, Pratilas CA, Pearson ADJ, Tseng L, Nebot N, Green S, Russo MW, Whitlock JA. A Phase I and Pharmacokinetic Study of Oral Dabrafenib in Children and Adolescent Patients with Recurrent or Refractory BRAF V600 Mutation-Positive Solid Tumors. Clin Cancer Res. 2019 Dec 15;25(24):7294-7302. doi: 10.1158/1078-0432.CCR-17-3572. Epub 2019 Sep 10.
Wang J, Yao Z, Jonsson P, Allen AN, Qin ACR, Uddin S, Dunkel IJ, Petriccione M, Manova K, Haque S, Rosenblum MK, Pisapia DJ, Rosen N, Taylor BS, Pratilas CA. A Secondary Mutation in BRAF Confers Resistance to RAF Inhibition in a BRAFV600E-Mutant Brain Tumor. Cancer Discov. 2018 Sep;8(9):1130-1141. doi: 10.1158/2159-8290.CD-17-1263. Epub 2018 Jun 7.
FG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
FG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
FG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
FG004
Part 2 (Tumor Specific Expansion): Cohort 1 Low-Grade Gliomas (LGG)
Subjects with low-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
FG005
Part 2 (Tumor Specific Expansion): Cohort 2 High-Grade Gliomas (HGG)
Subjects with high-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
FG006
Part 2 (Tumor Specific Expansion): Cohort 3 Langerhans Cell Histiocytosis (LCH)
Subjects with LCH with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
FG007
Part 2 (Tumor Specific Expansion): Cohort 4 Miscellaneous Tumors (Other)
Subjects with other tumors with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
FG0003 subjects
FG00110 subjects
FG0028 subjects
FG0036 subjects
FG00417 subjects
FG00528 subjects
FG00611 subjects
FG0072 subjects
DLT Evaluable Population
Part 1 subjects fulfilling the All Treated population criteria, and having received an adequate treatment for the first 28 days to enable an appropriate evaluation of study drug related DLTs
FG0003 subjects
FG00110 subjects
FG0028 subjects
FG0036 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
PK Population
Subjects fulfilling the All Treated population criteria and for whom pharmacokinetic sample(s) were obtained and analyzed
FG0003 subjects
FG00110 subjects
FG0028 subjects
FG0036 subjects
FG00417 subjects
FG00528 subjects
FG00611 subjects
FG0072 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
NOT COMPLETED
FG0003 subjects
FG00110 subjects
FG0028 subjects
FG0036 subjects
FG00417 subjects
FG00528 subjects
FG00611 subjects
FG0072 subjects
Type
Comment
Reasons
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
Withdrawal by Subject
FG0002 subjects
FG0017 subjects
FG0025 subjects
FG0034 subjects
FG004
Enrolled in a rollover study
FG0000 subjects
FG0013 subjects
FG0022 subjects
FG0031 subjects
FG004
Progressive disease
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
BG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
BG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
BG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
BG004
Part 2 (Tumor Specific Expansion): Cohort 1 Low-Grade Gliomas (LGG)
Subjects with low-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
BG005
Part 2 (Tumor Specific Expansion): Cohort 2 High-Grade Gliomas (HGG)
Subjects with high-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
BG006
Part 2 (Tumor Specific Expansion): Cohort 3 Langerhans Cell Histiocytosis (LCH)
Subjects with LCH with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
BG007
Part 2 (Tumor Specific Expansion): Cohort 4 Miscellaneous Tumors (Other)
Subjects with other tumors with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0003
BG00110
BG0028
BG0036
BG00417
BG00528
BG00611
BG0072
BG00885
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG0009.33± 5.132
BG00111.30± 5.355
BG0026.58± 5.445
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0001
BG0015
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Incidence of Treatment Emergent Adverse Events (AEs) in Part 1 (Dose Escalation)
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Events, Serious Adverse Events and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.
Safety population. Deaths occurring more than 28 days after the last dose of study drug were not included in the on-treatment deaths. All deaths included on-treatment deaths and those occurring more than 28 days after the last dose of study drug.
Posted
Count of Participants
Participants
From study treatment start date till 28 days safety follow-up, assessed up to approximately 90 months
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Units
Counts
Participants
OG0003
OG00110
OG0028
OG003
Title
Denominators
Categories
All deaths
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Maximum Concentration (Cmax) of Dabrafenib
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax of dabrafenib was listed and summarized using descriptive statistics.
Pharmacokinetic population. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Week 1 Day 1, Week 3 Day 15
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Primary
Area Under the Concentration-time Curve Over the Dosing Interval (AUC(0-τ)) and AUC From Zero to Infinity (AUC(0-inf)) of Dabrafenib
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUC(0-τ) and AUC(0-inf) of dabrafenib were to be listed and summarized using descriptive statistics.
Pharmacokinetic population. Due to limited dabrafenib PK data collected for Day 1 (up to 4 hours post-dose PK data only), no reliable AUC(0-t) and AUC (0-inf) PK parameters were collected/calculated.
Posted
Week 1 Day 1
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
Pre-dose (Trough) Concentration (C Tau) of Dabrafenib and Its Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Pre-dose (trough) concentration (C tau) was to be listed and summarized using descriptive statistics for dabrafenib and its metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]).
Pharmacokinetic population. For each parameter, only participants with an evaluable PK sample collected were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Week 3 Day 15
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
The AUC(0-t) of Dabrafenib Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC[0-t]) dabrafenib metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]) were to be listed and summarized using descriptive statistics.
Pharmacokinetic population. Due to limited dabrafenib PK data collected for Day 1 (up to 4 hours post-dose PK data only), no reliable AUC(0-t) PK parameters were collected/calculated.
Posted
Week 1 Day 1, Week 3 Day 15
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
The AUC(0-tau) of Dabrafenib and Its Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-tau) of dabrafenib and its metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]) were to be listed and summarized using descriptive statistics.
Pharmacokinetic population. Due to limited dabrafenib PK data collected for Day 1 (up to 4 hours post-dose PK data only), no reliable AUC(0-tau) PK parameters were collected/calculated.
Posted
Week 1 Day 1, Week 3 Day 15
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F) of Dabrafenib
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. CL/F of dabrafenib was to be listed and summarized using descriptive statistics.
Pharmacokinetic population. Due to limited dabrafenib PK data collected for Day 1 (up to 4 hours post-dose PK data only), no reliable CL/F PK parameters were collected/calculated.
Posted
Week 1 Day 1, Week 3 Day 15
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
Maximum Concentration (Cmax) of Dabrafenib Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax of dabrafenib metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]) were listed and summarized using descriptive statistics.
Pharmacokinetic population. For each parameter, only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Week 1 Day 1, Week 3 Day 15
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
Time to Reach Maximum (Peak) Plasma Concentration Following Drug Administration (Tmax) of Dabrafenib and Its Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was listed and summarized using descriptive statistics for dabrafenib and its metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]).
Pharmacokinetic population. For each parameter, only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Median
Full Range
Hour (hr)
Week 1 Day 1, Week 3 Day 15
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
Elimination Half Life (T½) of Dabrafenib and Its Metabolites
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. T1/2 of dabrafenib and its metabolites (hydroxy-dabrafenib [GSK2285403], carboxy-dabrafenib [GSK2298683], and desmethyl-dabrafenib [GSK2167542]) was listed and summarized using descriptive statistics.
Pharmacokinetic population. For each parameter, only participants with an evaluable PK sample collected were included in the analysis.
Posted
Mean
Standard Deviation
Hour (hr)
Week 3 Day 15
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
Incidence of Treatment Emergent Adverse Events (AEs) in Part 2 (Tumor Specific Expansion)
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Events, Serious Adverse Event and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Safety population. Deaths occurring more than 28 days after the last dose of study drug were not included in the on-treatment deaths. All deaths included on-treatment deaths and those occurring more than 28 days after the last dose of study drug.
Posted
Count of Participants
Participants
From study treatment start date till 28 days safety follow-up, assessed up to approximately 90 months
ID
Title
Description
OG000
Part 2 (Tumor Specific Expansion): Cohort 1 Low-Grade Gliomas (LGG)
Subjects with low-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
OG001
Part 2 (Tumor Specific Expansion): Cohort 2 High-Grade Gliomas (HGG)
Subjects with high-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
Secondary
Best Overall Response Based on Investigator Assessment Per Response Assessment in Neuro-Oncology (RANO) Criteria for Low Grade Glioma (LLG) Subjects
Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR).based on Response Assessment in Neuro-Oncology (RANO) criteria for Low Grade Glioma (LLG) and High Grade Glioma (HGG) subjects.
All treated population
Posted
Count of Participants
Participants
Up to 6 months
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
Best Overall Response Based on Investigator Assessment Per Response Assessment in Neuro-Oncology (RANO) Criteria for High Grade Glioma (HGG) Subjects
Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR).based on Response Assessment in Neuro-Oncology (RANO) criteria for Low Grade Glioma (LLG) and High Grade Glioma (HGG) subjects.
All treated population
Posted
Count of Participants
Participants
Up to 6 months
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Secondary
Effect of Weight on Total Apparent Clearance (CL/F) of Dabrafenib Estimated With a PopPK Model
The population pharmacokinetic (PopPK) model of Dabrafenib can be described using a two-compartment model with a delayed 1st order absorption (Alag1, Ka) and an inducible elimination (CL/F) that consists of a base clearance (constant over time, CL0/F) and a dose- and time-dependent inducible clearance (CLind/F). The PopPK analysis examined the influence of demographics (i.e., weight) on the pharmacokinetics of dabrafenib. The effect of weight on total apparent clearance (CL/F) of dabrafenib estimated with the PopPK model is summarized in this record.
All subjects who received at least one dose of dabrafenib in Part 1 and 2 and provided an evaluable PK profile. All trametinib and dabrafenib concentration-time data were combined and included in a population PK analysis that examined the influence of demographics on the PK of study treatment.
Posted
Number
coefficient
Day 1-Predose, 0.5, 2 and 4 hours post dose; Day 15-Predose, 0, 0.5, 1, 2, 3, 4, 6 and 8 hours post dose.
ID
Title
Description
OG000
Part 1 and Part 2 - All Participants With PK Data
Participants in the study (all doses and all tumor types) with available pharmacokinetic data
Units
Counts
Participants
Secondary
Effect of Weight on Volume of Distribution (V/F) of Dabrafenib Estimated With a PopPK Model
The population pharmacokinetic (PopPK) model of Dabrafenib can be described using a two-compartment model with a delayed 1st order absorption (Alag1, Ka) and an inducible elimination (CL/F) that consists of a base clearance (constant over time, CL0/F) and a dose- and time-dependent inducible clearance (CLind/F). The PopPK analysis examined the influence of demographics (i.e., weight) on the pharmacokinetics of dabrafenib. The effect of weight on volume of distribution (V/F) of dabrafenib estimated with the PopPK model is summarized in this record.
All subjects who received at least one dose of dabrafenib in Part 1 and 2 and provided an evaluable PK profile. All trametinib and dabrafenib concentration-time data were combined and included in a population PK analysis that examined the influence of demographics on the PK of study treatment.
Posted
Number
coefficient
Day 1-Predose, 0.5, 2 and 4 hours post dose; Day 15-Predose, 0, 0.5, 1, 2, 3, 4, 6 and 8 hours post dose.
ID
Title
Description
OG000
Part 1 and Part 2 - All Participants With PK Data
Participants in the study (all doses and all tumor types) with available pharmacokinetic data
Units
Counts
Participants
Secondary
Effect of Weight on Absorption Rate (ka) of Dabrafenib Estimated With a PopPK Model
The population pharmacokinetic (PopPK) model of Dabrafenib can be described using a two-compartment model with a delayed 1st order absorption (Alag1, Ka) and an inducible elimination (CL/F) that consists of a base clearance (constant over time, CL0/F) and a dose- and time-dependent inducible clearance (CLind/F). The PopPK analysis examined the influence of demographics (i.e., weight) on the pharmacokinetics of dabrafenib. The effect of weight on absorption rate (ka) of dabrafenib estimated with a PopPK model is summarized in this record.
All subjects who received at least one dose of dabrafenib in Part 1 and 2 and provided an evaluable PK profile. The covariate weight did not meet the pre-specified criteria to be considered a significant covariate on Ka based on the goodness-of-fit plots and the decrease of the objective function provided by the PopPK software (NONMEM). Therefore, effect of weight on Ka could not be calculated.
Posted
Number
coefficient
Day 1-Predose, 0.5, 2 and 4 hours post dose; Day 15-Predose, 0, 0.5, 1, 2, 3, 4, 6 and 8 hours post dose.
ID
Title
Description
OG000
Part 1 and Part 2 - All Participants With PK Data
Participants in the study (all doses and all tumor types) with available pharmacokinetic data
Units
Counts
Participants
Secondary
Effect of Weight on Coefficients for Significant Covariates of Dabrafenib Estimated With a PopPK Model
The population pharmacokinetic (PopPK) model of Dabrafenib can be described using a two-compartment model with a delayed 1st order absorption (Alag1, Ka) and an inducible elimination (CL/F) that consists of a base clearance (constant over time, CL0/F) and a dose- and time-dependent inducible clearance (CLind/F). The PopPK analysis examined the influence of demographics (i.e., weight) on the pharmacokinetics of dabrafenib. The effect of weight on coefficients for significant covariates of dabrafenib estimated with a PopPK model is summarized in this record.
All subjects who received at least one dose of dabrafenib in Part 1 and 2 and provided an evaluable PK profile. The covariate weight did not meet the pre-specified criteria to be considered a significant covariate based on the goodness-of-fit plots and the decrease of the objective function provided by the PopPK software (NONMEM). Therefore, effect of weight on coefficients for significant covariates of dabrafenib could not be calculated.
Posted
Number
coefficient
Day 1-Predose, 0.5, 2 and 4 hours post dose; Day 15-Predose, 0, 0.5, 1, 2, 3, 4, 6 and 8 hours post dose.
ID
Title
Description
OG000
Part 1 and Part 2 - All Participants With PK Data
Participants in the study (all doses and all tumor types) with available pharmacokinetic data
Units
Counts
Post-Hoc
All Collected Deaths in Parts I and II
On treatment deaths were collected from FPFT up to 28 days after study drug discontinuation, for a maximum duration of 360 weeks in Part I (treatment duration ranged from 5.6 to 356.0 weeks) and a maximum duration of 300 weeks in Part II (treatment duration ranged from 0.3 to 296.0 weeks).
Deaths post treatment survival follow up were collected after the on- treatment period, up to approximately 7 years. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.
Clinical database population; all treated patients.
Posted
Count of Participants
Participants
up to 360 weeks (on-treatment in Part I), up to 300 weeks (on-treatment in Part II), up to approximately 7 years (study duration)
ID
Title
Description
OG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
Time Frame
Adverse events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 360 weeks in Part I (treatment duration ranged from 5.6 to 356.0 weeks) and a maximum duration of 300 weeks in Part II (treatment duration ranged from 0.3 to 296.0 weeks).
Description
Any sign or symptom that occurs during the treatment period plus 28 days post-treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1 (Dose Escalation): Dabrafenib Treatment (3 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
0
3
0
3
3
3
EG001
Part 1 (Dose Escalation): Dabrafenib Treatment (3.75 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
0
10
5
10
10
10
EG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
0
8
5
8
8
8
EG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
1
6
3
6
6
6
EG004
Part 2 (Tumor Specific Expansion): Cohort 1 Low-Grade Gliomas (LGG)
Subjects with low-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
0
17
7
17
17
17
EG005
Part 2 (Tumor Specific Expansion): Cohort 2 High-Grade Gliomas (HGG)
Subjects with high-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
0
28
13
28
26
28
EG006
Part 2 (Tumor Specific Expansion): Cohort 3 Langerhans Cell Histiocytosis (LCH)
Subjects with LCH with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
0
11
6
11
11
11
EG007
Part 2 (Tumor Specific Expansion): Cohort 4 Miscellaneous Tumors (Other)
Subjects with other tumors with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
0
2
0
2
2
2
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Disseminated intravascular coagulation
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG0030 affected6 at risk
EG004
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Disease progression
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
General physical health deterioration
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Pyrexia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Appendicitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Catheter site infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Corynebacterium infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Croup infectious
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Device related infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Influenza
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Oral herpes
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Pharyngitis streptococcal
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Pseudomonal bacteraemia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Salmonellosis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Skin infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Staphylococcal infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Varicella
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Accidental overdose
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Overdose
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Shunt malfunction
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Stroke-like migraine attacks after radiation therapy
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Blood culture positive
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Ejection fraction decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hypophagia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Epstein-Barr virus associated lymphoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Metastases to meninges
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Tumour haemorrhage
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Ataxia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Depressed level of consciousness
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Headache
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hydrocephalus
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Intracranial pressure increased
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Meningeal disorder
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Presyncope
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Seizure
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Device occlusion
Product Issues
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Dermatitis bullous
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Pityriasis rosea
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hypotension
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0002 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG0033 affected6 at risk
EG0045 affected17 at risk
EG0054 affected28 at risk
EG0063 affected11 at risk
EG0070 affected2 at risk
Leukocytosis
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Monocytosis
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Neutrophilia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Thrombocytosis
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Cardiac disorder
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Mitral valve incompetence
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Palpitations
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Tricuspid valve disease
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Cerumen impaction
Ear and labyrinth disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Deafness
Ear and labyrinth disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Excessive cerumen production
Ear and labyrinth disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
External ear inflammation
Ear and labyrinth disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Adrenal insufficiency
Endocrine disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Precocious puberty
Endocrine disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Blepharospasm
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Dark circles under eyes
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Diplopia
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Dry eye
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Eye pain
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Eye pruritus
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Hypermetropia
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Keratitis
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Myopia
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Ocular hyperaemia
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Optic nerve disorder
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Papilloedema
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Periorbital swelling
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Photophobia
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Retinal exudates
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Scleral disorder
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Uveitis
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Vernal keratoconjunctivitis
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Vision blurred
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Visual acuity reduced
Eye disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0014 affected10 at risk
EG0021 affected8 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG003
Angular cheilitis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Chapped lips
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Cheilitis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Cheilosis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Chronic gastritis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0023 affected8 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0024 affected8 at risk
EG003
Duodenal ulcer
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Duodenitis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Gastrointestinal pain
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Glossodynia
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0015 affected10 at risk
EG0022 affected8 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Oral disorder
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Oral mucosal eruption
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Paraesthesia oral
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Tongue ulceration
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0002 affected3 at risk
EG0015 affected10 at risk
EG0025 affected8 at risk
EG003
Asthenia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Catheter site erythema
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Catheter site extravasation
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Chest pain
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Chills
General disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Complication associated with device
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Face oedema
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Facial pain
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Fatigue
General disorders
MedDRA (23.1)
Systematic Assessment
EG0002 affected3 at risk
EG0016 affected10 at risk
EG0022 affected8 at risk
EG003
Feeling hot
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Gait disturbance
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Influenza like illness
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Localised oedema
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Malaise
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Oedema peripheral
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Pain
General disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Peripheral swelling
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Pyrexia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0003 affected3 at risk
EG0015 affected10 at risk
EG0027 affected8 at risk
EG003
Xerosis
General disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
COVID-19
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Candida infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Carbuncle
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Coronavirus infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Croup infectious
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Ear infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0022 affected8 at risk
EG003
Enterobiasis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Enterovirus infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Eye infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Folliculitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0021 affected8 at risk
EG003
Fungal infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Fungal skin infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Furuncle
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Gastritis viral
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Groin abscess
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hand-foot-and-mouth disease
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Impetigo
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Influenza
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Metapneumovirus infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Onychomycosis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Oral herpes
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Otitis externa
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Otitis media
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0023 affected8 at risk
EG003
Otitis media acute
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Parainfluenzae virus infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Paronychia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Pertussis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0002 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Pharyngitis streptococcal
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Pitted keratolysis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Pustule
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Rash pustular
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0022 affected8 at risk
EG003
Respiratory syncytial virus infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG003
Rhinovirus infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Skin bacterial infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Skin infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Staphylococcal infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Streptococcal infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Tinea cruris
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Tinea infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Tinea pedis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Tooth infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Tracheostomy infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0025 affected8 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Varicella
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Vascular device infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Viral infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Viral rash
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Vulval abscess
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Vulvovaginal candidiasis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Animal bite
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Animal scratch
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG003
Clavicle fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0023 affected8 at risk
EG003
Foot fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Gastrostomy tube site complication
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Hand fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Nail avulsion
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Overdose
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Radius fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Scar
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Upper limb fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Wound
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Activated partial thromboplastin time prolonged
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0014 affected10 at risk
EG0022 affected8 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0023 affected8 at risk
EG003
Blood albumin decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Blood alkaline phosphatase decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Blood bilirubin decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Blood calcium decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Blood chloride increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Blood creatinine decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Blood fibrinogen decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Blood luteinising hormone increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Blood prolactin abnormal
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Blood urea decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
C-reactive protein increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Carbon dioxide decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Cardiac murmur
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Creatinine urine decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Ejection fraction decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Eosinophil count increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Haemoglobin increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0022 affected8 at risk
EG003
International normalised ratio increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Low density lipoprotein increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Platelet count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0023 affected8 at risk
EG003
Platelet count increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Protein total increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Protein urine present
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Red blood cell count increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Respiratory rate decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Transaminases increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Urine albumin/creatinine ratio increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Urine analysis abnormal
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Urine protein/creatinine ratio increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Weight decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0022 affected8 at risk
EG003
Weight increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0022 affected8 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0023 affected8 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0022 affected8 at risk
EG003
Folate deficiency
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Hyperchloraemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0013 affected10 at risk
EG0023 affected8 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0021 affected8 at risk
EG003
Hyperlipidaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hypermagnesaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hypernatraemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0022 affected8 at risk
EG003
Hyperphosphataemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0002 affected3 at risk
EG0013 affected10 at risk
EG0024 affected8 at risk
EG003
Iron deficiency
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Metabolic acidosis
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Polydipsia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Vitamin B12 deficiency
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0014 affected10 at risk
EG0022 affected8 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0021 affected8 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Ligament pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Limb mass
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Muscle contracture
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0020 affected8 at risk
EG003
Musculoskeletal deformity
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0020 affected8 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0014 affected10 at risk
EG0022 affected8 at risk
EG003
Acrochordon
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Lip neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Melanocytic naevus
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG003
Neoplasm skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Skin papilloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Xanthogranuloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Altered state of consciousness
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Amnesia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Ataxia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0013 affected10 at risk
EG0022 affected8 at risk
EG003
Dysaesthesia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Dysmetria
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Facial nerve disorder
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Headache
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0018 affected10 at risk
EG0023 affected8 at risk
EG003
Hemianopia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hypersomnia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Lethargy
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Migraine
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Muscle spasticity
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Nervous system disorder
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Nystagmus
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Oculofacial paralysis
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Partial seizures
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Periodic limb movement disorder
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Psychomotor hyperactivity
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Seizure
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0022 affected8 at risk
EG003
Syncope
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Tremor
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
VIth nerve paralysis
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Visual field defect
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Affect lability
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Aggression
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Agitation
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0022 affected8 at risk
EG003
Anger
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG003
Attention deficit hyperactivity disorder
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Depression
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Dysphemia
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Emotional disorder
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Hallucination
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Irritability
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Middle insomnia
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Mood altered
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Haemoglobinuria
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Microalbuminuria
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Polyuria
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0024 affected8 at risk
EG003
Renal tubular disorder
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Urinary tract pain
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Amenorrhoea
Reproductive system and breast disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Testicular pain
Reproductive system and breast disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Adenoidal hypertrophy
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Catarrh
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0015 affected10 at risk
EG0024 affected8 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Hypocapnia
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Laryngeal inflammation
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0013 affected10 at risk
EG0021 affected8 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Respiratory acidosis
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Restrictive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Sleep apnoea syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Sneezing
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Tachypnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Tonsillar hypertrophy
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0013 affected10 at risk
EG0020 affected8 at risk
EG003
Blister
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Cafe au lait spots
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Dermal cyst
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Dermatitis bullous
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Dermatitis diaper
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Dermatitis exfoliative generalised
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0016 affected10 at risk
EG0023 affected8 at risk
EG003
Ecchymosis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Eczema asteatotic
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Ephelides
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0022 affected8 at risk
EG003
Erythema nodosum
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hair colour changes
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hair texture abnormal
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Hidradenitis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hyperkeratosis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0023 affected8 at risk
EG003
Ingrown hair
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Intertrigo
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Keloid scar
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Keratosis pilaris
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0013 affected10 at risk
EG0023 affected8 at risk
EG003
Lentigo
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Macule
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Miliaria
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Nail discolouration
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Nail disorder
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Nail pigmentation
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Neurodermatitis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Onychomadesis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Pain of skin
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Palmar-plantar erythrodysaesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Palmoplantar keratoderma
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Panniculitis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0021 affected8 at risk
EG003
Papule
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Photosensitivity reaction
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0022 affected8 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0014 affected10 at risk
EG0022 affected8 at risk
EG003
Rash erythematous
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0013 affected10 at risk
EG0023 affected8 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0024 affected8 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Rash vesicular
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Scab
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Seborrhoea
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Seborrhoeic dermatitis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Skin discolouration
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Skin disorder
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Skin exfoliation
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0022 affected8 at risk
EG003
Skin fissures
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Skin hyperpigmentation
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Skin hypertrophy
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0020 affected8 at risk
EG003
Skin induration
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Skin lesion
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0013 affected10 at risk
EG0022 affected8 at risk
EG003
Skin mass
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0020 affected8 at risk
EG003
Skin odour abnormal
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0021 affected8 at risk
EG003
Xeroderma
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Yellow skin
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Steroid therapy
Surgical and medical procedures
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Flushing
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Haematoma
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected10 at risk
EG0020 affected8 at risk
EG003
Hot flush
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Hypertension
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected10 at risk
EG0021 affected8 at risk
EG003
Hypotension
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected10 at risk
EG0022 affected8 at risk
EG003
Venous thrombosis
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected10 at risk
EG0020 affected8 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0003
OG00110
OG0028
OG0036
OG00427
OG00531
Title
Denominators
Categories
Week 1 Day 1
ParticipantsOG0002
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
ParticipantsOG00427
ParticipantsOG00531
Title
Measurements
OG0001820± 38.0
OG0011250± 61.5
OG0021250± 529.9
OG003
Week 3 Day 15
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0003
OG00110
OG0028
OG0036
OG00426
OG00529
Title
Denominators
Categories
dabrafenib
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
ParticipantsOG00426
ParticipantsOG00529
Title
Measurements
OG00011.9± 276.5
OG00139.8± 176.1
OG00250.7± 121.0
OG003
hydroxy-dabrafenib
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
carboxy-dabrafenib
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
desmethyl-dabrafenib
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0003
OG00110
OG0028
OG0036
OG00427
OG00531
Title
Denominators
Categories
hydroxy-dabrafenib @ Week 1 Day 1
ParticipantsOG0002
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
ParticipantsOG00426
ParticipantsOG00531
Title
Measurements
OG000811± 24.7
OG001662± 66.7
OG002473± 1643.7
OG003
hydroxy-dabrafenib @ Week 3 Day 15
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
carboxy-dabrafenib @ Week 1 Day 1
ParticipantsOG0002
ParticipantsOG00110
ParticipantsOG0027
ParticipantsOG0036
carboxy-dabrafenib @ Week 3 Day 15
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
desmethyl-dabrafenib @ Week 1 Day 1
ParticipantsOG0002
ParticipantsOG00110
ParticipantsOG0026
ParticipantsOG0036
desmethyl-dabrafenib @ Week 3 Day 15
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0003
OG00110
OG0028
OG0036
OG00427
OG00531
Title
Denominators
Categories
dabrafenib @ Week 1 Day 1
ParticipantsOG0002
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
ParticipantsOG00427
ParticipantsOG00531
Title
Measurements
OG0002.00(2.00 to 2.00)
OG0012.00(2.00 to 4.00)
OG0022.00(0.50 to 4.00)
OG003
dabrafenib @ Week 3 Day 15
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
hydroxy-dabrafenib @ Week 1 Day 1
ParticipantsOG0002
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
hydroxy-dabrafenib @ Week 3 Day 15
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
carboxy-dabrafenib @ Week 1 Day 1
ParticipantsOG0002
ParticipantsOG00110
ParticipantsOG0027
ParticipantsOG0036
carboxy-dabrafenib @ Week 3 Day 15
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
desmethyl-dabrafenib @ Week 1 Day 1
ParticipantsOG0002
ParticipantsOG00110
ParticipantsOG0026
ParticipantsOG0036
desmethyl-dabrafenib @ Week 3 Day 15
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 4,5 mg/kg
All patients at recommended dose phase 2 (RP2D) of 4,5 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
OG005
Part 2 (Tumor Specific Expansion): All Patients at Recommended Dose Phase 2 (RP2D) of 5.25 mg/kg
All patients at recommended dose phase 2 (RP2D) of 5.25 mg/kg in Part 2 study cohorts (Cohort 1 Low-Grade Gliomas (LGG), Cohort 2 High-Grade Gliomas (HGG), Cohort 3 Langerhans cell histiocytosis (LCH) and Cohort 4 Miscellaneous tumors including melanoma and papillary thyroid carcinoma (Other)) were pooled together.
Units
Counts
Participants
OG0003
OG00110
OG0028
OG0036
OG00425
OG00529
Title
Denominators
Categories
dabrafenib
ParticipantsOG0003
ParticipantsOG00110
ParticipantsOG0028
ParticipantsOG0036
ParticipantsOG00425
ParticipantsOG00529
Title
Measurements
OG0001.98± 0.687
OG0012.85± 1.58
OG0022.74± 0.840
OG003
hydroxy-dabrafenib
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
carboxy-dabrafenib
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
desmethyl-dabrafenib
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
OG002
Part 2 (Tumor Specific Expansion): Cohort 3 Langerhans Cell Histiocytosis (LCH)
Subjects with LCH with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
OG003
Part 2 (Tumor Specific Expansion): Cohort 4 Miscellaneous Tumors (Other)
Subjects with other tumors with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
Units
Counts
Participants
OG00017
OG00128
OG00211
OG0032
Title
Denominators
Categories
All deaths
Title
Measurements
OG0000
OG0011
OG0020
OG0030
On-treatment deaths
Title
Measurements
OG0000
OG0010
OG0020
OG003
Adverse Events (AEs)
Title
Measurements
OG00017
OG00126
OG00211
OG003
AEs suspected to be drug related
Title
Measurements
OG00016
OG00126
OG00211
OG003
Serious Adverse Events (SAEs)
Title
Measurements
OG0007
OG00113
OG0026
OG003
SAEs suspected to be drug related
Title
Measurements
OG0001
OG0013
OG0022
OG003
Fatal SAEs
Title
Measurements
OG0000
OG0011
OG0020
OG003
Fatal SAEs suspected to be drug related
Title
Measurements
OG0000
OG0010
OG0020
OG003
AEs leading to discontinuation
Title
Measurements
OG0002
OG0011
OG0021
OG003
AEs requiring dose interruptions
Title
Measurements
OG00010
OG00113
OG0027
OG003
AEs requiring dose reductions
Title
Measurements
OG0002
OG0014
OG0022
OG003
AEs requiring dose reductions or interruptions
Title
Measurements
OG00010
OG00113
OG0027
OG003
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 2 (Tumor Specific Expansion): Cohort 1 Low-Grade Gliomas (LGG)
Subjects with low-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
OG004
All LGG Subjects at Recommended Phase 2 Dose (RP2D)
All LGG patients who have been assigned to Recommended Phase II Dose (RP2D) across Part 1 and Part 2.
OG005
All LGG Subjects
All LGG subjects in the study
Units
Counts
Participants
OG0004
OG0016
OG0026
OG00317
OG00424
OG00533
Title
Denominators
Categories
Title
Measurements
OG0003
OG0015
OG0024
OG00312
OG00417
OG00524
OG002
Part 2 (Tumor Specific Expansion): Cohort 2 High-Grade Gliomas (HGG)
Subjects with high-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
OG003
All HGG Subjects at Recommended Phase 2 Dose (RP2D)
All HGG patients who have been assigned to Recommended Phase II Dose (RP2D) across Part 1 and Part 2.
OG004
All HGG Subjects
All HGG subjects in the study
Units
Counts
Participants
OG0003
OG0014
OG00228
OG00328
OG00435
Title
Denominators
Categories
Title
Measurements
OG0002
OG0011
OG0027
OG0037
OG00410
OG00085
Title
Denominators
Categories
Title
Measurements
OG0000.223
OG00085
Title
Denominators
Categories
Title
Measurements
OG0000.593
OG00085
Title
Denominators
Categories
Title
Measurements
OG000NAN/A: covariate weight did not meet the pre-specified criteria required to calculate a result in the PopPK model
Participants
OG00085
Title
Denominators
Categories
Title
Measurements
OG000NAN/A: covariate weight did not meet the pre-specified criteria required to calculate a result in the PopPK model
OG002
Part 1 (Dose Escalation): Dabrafenib Treatment (4.5 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG003
Part 1 (Dose Escalation): Dabrafenib Treatment (5.25 mg/kg)
Repeat dose, dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). The RSD was built on the classic 3+3 design, but allowed for continued recruitment of subjects while the data from the first 3 subjects in each cohort was collected (up to 6 subjects per cohort). The starting dose was 3 mg/kg with subsequent dose levels: 3.75 mg/kg, 4.5 mg/kg, 5.25 mg/kg and 6.0 mg/kg.
OG004
Part 2 (Tumor Specific Expansion): Cohort 1 Low-Grade Gliomas (LGG)
Subjects with low-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
OG005
Part 2 (Tumor Specific Expansion): Cohort 2 High-Grade Gliomas (HGG)
Subjects with high-grade gliomas with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
OG006
Part 2 (Tumor Specific Expansion): Cohort 3 Langerhans Cell Histiocytosis (LCH)
Subjects with LCH with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.
OG007
Part 2 (Tumor Specific Expansion): Cohort 4 Miscellaneous Tumors (Other)
Subjects with other tumors with BRAF V600 mutations will receive the single selected final dose (based on MTD and the age of the subjects) from Part 1 on Day 1. Repeat dosing will begin from Day 2, twice daily till end of study.