A Study of E7080 Alone, and in Combination With Everolimu... | NCT01136733 | Trialant
NCT01136733
Sponsor
Eisai Inc.
Status
Completed
Last Update Posted
Feb 27, 2019Actual
Enrollment
173Actual
Phase
Phase 1Phase 2
Conditions
Metastatic Renal Cell Carcinoma
Interventions
Lenvatinib
Everolimus
Countries
United States
Czechia
Poland
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT01136733
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
E7080-G000-205
Secondary IDs
Not provided
Brief Title
A Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior Vascular Endothelial Growth Factor (VEGF)-Targeted Treatment
Official Title
An Open-Label, Multicenter, Phase 1b/2 Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment
Acronym
Not provided
Organization
Eisai Inc.INDUSTRY
Status Module
Record Verification Date
Jan 2018
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
Aug 5, 2010Actual
Primary Completion Date
Jun 13, 2014Actual
Completion Date
Feb 8, 2018Actual
First Submitted Date
May 26, 2010
First Submission Date that Met QC Criteria
Jun 2, 2010
First Posted Date
Jun 3, 2010Estimated
Results Waived
Not provided
Results First Submitted Date
Nov 23, 2016
Results First Submitted that Met QC Criteria
Feb 7, 2019
Results First Posted Date
Feb 27, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Apr 18, 2016
Certification/Extension First Submitted that Passed QC Review
Apr 18, 2016
Certification/Extension First Posted Date
May 17, 2016Estimated
Last Update Submitted Date
Feb 7, 2019
Last Update Posted Date
Feb 27, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Eisai Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
This is an open-label, multicenter, Phase 1b/2 study of lenvatinib alone and in combination with everolimus in subjects with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted treatment.
Detailed Description
Not provided
Conditions Module
Conditions
Metastatic Renal Cell Carcinoma
Keywords
Unresectable advanced or metastatic renal cell carcinoma
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
173Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Lenvatinib
Experimental
Drug: Lenvatinib
Lenvatinib plus Everolimus
Experimental
Drug: Lenvatinib
Drug: Everolimus
Everolimus
Active Comparator
Drug: Everolimus
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Lenvatinib
Drug
taken orally, once a day
Lenvatinib
Lenvatinib plus Everolimus
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT)
A DLT was defined as either a treatment-related failure to administer greater than or equal to (>=) 75% of the planned dosage of lenvatinib/everolimus or a specific National Cancer Institute Common Toxicity Criteria (NCI CTC) >= Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care daily living activities) hematologic or nonhematologic toxicities considered to be possibly related to lenvatinib and/or everolimus therapy assessed during the first treatment cycle of each dose level. Higher grade indicates more severe toxicity.
First dose of study drug (Cycle 1 Day 1) to end of first 4 weeks of therapy (Cycle 1)
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 (RP2) Dose
The highest dose level resulting in 0 or 1 DLT in 6 participants was to be considered the MTD of Phase 1b. Once the MTD was established, the participant cohort was expanded to a minimum of 10 participants. The MTD was confirmed by assessing DLTs during Cycle 1 and intolerable toxicities (i.e., not manageable with dose interruption and/or reduction) during Cycle 2 of therapy. Once the dose of lenvatinib/everolimus combination to be used in the succeeding Phase 2 part of the study was established, enrollment into Phase 2 was started. The RP2 dose was the same as the confirmed MTD and was used for the Phase 2 Treatment Arm A of this study.
First dose of study drug (Cycle 1 Day 1) to end of Cycle 2 (1 cycle = 28 days/4 weeks)
Phase 2: Progression-Free Survival (PFS)
PFS was defined as the time (in months) from the date of first dose of study drug to the first documentation of disease progression or death, whichever occurred first. Kaplan-Meier (K-M) estimates were used to estimate median PFS, presented with 2-sided 95% confidence intervals (CIs). Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease using computed tomography (CT) or magnetic resonance imaging (MRI) and scan acquisition techniques (including use or nonuse of intravenous (IV) contrast). Tumor response was determined at the site by the investigator and radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in the evaluation of the tumor assessment scans. The date of objective disease progression was defined as the earliest date of radiological disease progression. Participants removed from therapy due to clinical progression with no radiologic confirmation were censored at their last radiologic assessment date.
Secondary Outcomes
Measure
Description
Time Frame
Phase 2: Overall Survival (OS)
OS was defined as the time (in months) from the date of randomization until date of death from any cause. Median survival time was calculated using K-M estimate for each treatment arm and presented with 2-sided 95% CIs. Participants who were lost to follow-up or alive at the data cutoff date (10 Dec 2014) were censored at the date the participants were last known to be alive.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Select Inclusion Criteria:
Histologically confirmed diagnosis of renal cell carcinoma.
Phase 2: Histological or cytological confirmation of predominant clear cell renal cell carcinoma (RCC) (original tissue diagnosis of RCC is acceptable).
Documented evidence of unresectable advanced or metastatic RCC. Phase 2: Radiographic evidence of disease progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Phase 2: One prior vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) for unresectable advanced or metastatic RCC.
Phase 2: Measurable disease meeting the following criteria: a.) at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short axis diameter for a lymph node which is serially measurable according to Modified RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI) or photography. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
Select Exclusion Criteria:
Phase 1b or Phase 2 specific per below:
Phase 1b only: Subjects with untreated or unstable metastasis to the central nervous system (CNS) are excluded. Subjects who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are eligible for Phase 1b only. Phase 2 only: Subjects with CNS (e.g., brain or leptomeningeal) metastasis are excluded.
Phase 2 only: More than one prior VEGF-targeted treatment for unresectable advanced or metastatic RCC.
Phase 1b or Phase 2 specific per below:
Phase 1b only: Prior exposure to lenvatinib. Phase 2 only: Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor.
Subjects should not have received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anticancer treatment. Major surgery within 3 weeks prior to the first dose of study drug.
Subjects having greater than 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.
Subjects with urine protein greater than or equal to 1 g/24 hours will be ineligible. Uncontrolled diabetes as defined by fasting serum glucose at 1.5 x ULN.
Phase 2 only: Active malignancy (except for renal cell carcinoma, melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
Known intolerance to any of the study drugs (or any of the excipients) and/or known hypersensitivity to rapamycins (e.g., sirolimus, everolimus, temsirolimus) or any of the excipients.
Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to toxicity will be ineligible.
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Periods
Title
Milestones
Reasons Not Completed
Phase 1b
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
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
No data available
No data is available for this block.
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
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
E7080, Lenvima, Kisplyx
Everolimus
Drug
taken orally, once a day
Everolimus
Lenvatinib plus Everolimus
Afinitor
Date of randomization into Phase 2 (Cycle 1 Day 1) to the date of first documentation of disease progression or death (whichever occurred first), assessed up to data cutoff date (13 Jun 2014), up to approximately 2 years and 3 months
Randomization (Cycle 1 Day 1) until date of death from any cause, assessed up to the data cutoff date (10 Dec 2014), up to approximately 2 years and 9 months
Phase 2: Objective Response Rate (ORR)
The ORR was defined as the percentage of participants who had the best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator, using RECIST 1.1 in the evaluation of MRI or CT scans of targeted lesions. Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease). The BOR was defined as the best response recorded from the start of the study treatment until discontinuation from the study. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR was calculated with exact 95% CIs using the method of Clopper and Pearson.
Randomization (Cycle 1 Day 1) until first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Disease Control Rate (DCR)
The DCR was defined as the percentage of participants who had a BOR of CR or PR or SD (minimum duration from randomization to SD greater than or equal to 7 weeks). Assessments were performed every 8 weeks and were based on investigator review data using RECIST 1.1. The 95% CI was constructed using the method of Clopper and Pearson. DCR = CR + PR + SD greater than or equal to 7 weeks.
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Durable Stable Disease (SD) Rate
The durable SD rate was defined as the percentage of participants whose BOR was SD and the duration of SD was greater than or equal to 23 weeks. The durable SD was based on investigator review data using RECIST 1.1. The 95% CI was constructed using the method of Clopper and Pearson.
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Clinical Benefit Rate (CBR)
The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (duration of SD was greater than or equal to 23 weeks) and was based on investigator review data using RECIST 1.1. The BOR was defined as the best response recorded from the start of study treatment until discontinuation from the study. There was no requirement for confirmatory measurement of PR or CR to deem either one the BOR. The 95% CI was constructed using the method of Clopper and Pearson. CBR = CR + PR + SD greater than or equal to 23 weeks.
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Summary of Plasma Concentrations of Lenvatinib for Sparse Pharmacokinetic (PK) Sampling for Phase 1b and Phase 2
Blood samples were collected during the Randomization Phase. Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose). Plasma concentrations of lenvatinib were measured and concentration data were summarized. The summary statistics at time points with one or more below the limit of quantitation (BLQ) values were calculated by assigning zero for each BLQ value.
Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
Summary of Blood Concentrations of Everolimus for Sparse PK Sampling for Phase 1b and Phase 2
Blood samples were collected during the Randomization Phase. Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose). Whole blood concentrations of everolimus were measured and concentration data were summarized. The summary statistics at time points with one or more BLQ values were calculated by assigning zero for each BLQ value.
Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC(0-24)) for Lenvatinib When Administered Alone or in Combination With Everolimus
Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling. Blood samples were analyzed for study drug using standardized methods. PK parameters for lenvatinib were derived from lenvatinib concentration data using non-compartmental methods. Data were compared via descriptive statistics between single agent and combination therapy.
Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
Maximum Concentration (Cmax) of Lenvatinib in Plasma When Administered Alone or in Combination With Everolimus
Cmax for lenvatinib was defined as the maximum observed concentration of lenvatinib in plasma following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured plasma concentration-time curves.
Phase 2: Cycle 1 Day 15
Time to Cmax (Tmax) for Lenvatinib When Administered Alone or in Combination With Everolimus
Tmax for lenvatinib was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach maximum concentration (Cmax) of lenvatinib in plasma.
Phase 2: Cycle 1 Day 15
Area Under the Blood Concentration-Time Curve From 0 to 24 Hours for Everolimus When Administered Alone or in Combination With Lenvatinib
Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling. Blood samples were analyzed for study drug using standardized methods. PK parameters for everolimus were derived from everolimus concentration data using non-compartmental methods. Data were compared via descriptive statistics between single agent and combination therapy.
Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
Maximum Concentration of Everolimus (Cmax) in Blood When Administered Alone or in Combination With Lenvatinib
Cmax for everolimus was defined as the maximum observed concentration of everolimus in blood following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured blood concentration-time curves.
Phase 2: Cycle 1 Day 15
Time to Cmax (Tmax) for Everolimus When Administered Alone or in Combination With Lenvatinib
Tmax for everolimus was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach the maximum concentration (Cmax) of everolimus in blood.
Phase 2: Cycle 1 Day 15
Orange
California
United States
San Diego
California
United States
Tampa
Florida
United States
Joliet
Illinois
United States
Louisville
Kentucky
United States
Annapolis
Maryland
United States
Bethesda
Maryland
United States
Boston
Massachusetts
United States
Tupelo
Mississippi
United States
New York
New York
United States
Tulsa
Oklahoma
United States
Charleston
South Carolina
United States
Dallas
Texas
United States
Brno
Czechia
Olomouc
Czechia
Prague
Czechia
Gdansk
Poland
Lodz
Poland
Szczecin
Poland
Warsaw
Poland
Barcelona
Spain
Córdoba
Spain
Madrid
Spain
Pamplona
Spain
Bristol
United Kingdom
Cambridge
United Kingdom
Cardiff
United Kingdom
Glasgow
United Kingdom
Guildford
United Kingdom
Ipswich
United Kingdom
Leicester
United Kingdom
London
United Kingdom
Manchester
United Kingdom
Metropolitan Borough of Wirral
United Kingdom
Southampton
United Kingdom
Surrey
United Kingdom
Derived
Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-1482. doi: 10.1016/S1470-2045(15)00290-9. Epub 2015 Oct 22.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18mg) and everolimus (5 mg) was once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
FG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
FG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
FG0007 subjectsParticipants in Phase 1b did not advance to Phase 2.
FG00111 subjectsParticipants in Phase 1b did not advance to Phase 2.
FG0022 subjectsParticipants in Phase 1b did not advance to Phase 2.
FG0030 subjectsParticipants in Phase 1b did not advance to Phase 2.
FG0040 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG0006 subjects
FG0016 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG0001 subjects
FG0015 subjects
FG0022 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0013 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Participant Choice
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Administrative-Withdrew Consent
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Clinical Progression
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Phase 2
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00451 subjectsParticipants in Phase 2 did not participate in Phase 1b.
FG00552 subjectsParticipants in Phase 2 did not participate in Phase 1b.
FG00650 subjectsParticipants in Phase 2 did not participate in Phase 1b.
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Disease Progression
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Full analysis set included all randomized participants.
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18 mg) and everolimus (5 mg) was once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
BG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
BG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
BG007
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0007
BG00111
BG0022
BG0030
BG00451
BG00552
BG00650
BG007173
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Geometric Mean
Standard Deviation
Years
Title
Denominators
Categories
Phase 1b
Title
Measurements
BG00058.0± 3.92
BG00158.1± 7.97
BG00261.0± 2.83
BG004
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0003
BG0012
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
Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT)
A DLT was defined as either a treatment-related failure to administer greater than or equal to (>=) 75% of the planned dosage of lenvatinib/everolimus or a specific National Cancer Institute Common Toxicity Criteria (NCI CTC) >= Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care daily living activities) hematologic or nonhematologic toxicities considered to be possibly related to lenvatinib and/or everolimus therapy assessed during the first treatment cycle of each dose level. Higher grade indicates more severe toxicity.
Safety analysis set included all participants who received at least one dose of study treatment.
Posted
Number
Participants
First dose of study drug (Cycle 1 Day 1) to end of first 4 weeks of therapy (Cycle 1)
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
OG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Counts
Participants
OG0007
OG00111
OG0022
OG003
Title
Denominators
Categories
Grade 3 abdominal pain
Title
Measurements
OG0001
OG0010
OG0020
Grade 2 fatigue with Grade 1 GI reflux & anorexia
Primary
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 (RP2) Dose
The highest dose level resulting in 0 or 1 DLT in 6 participants was to be considered the MTD of Phase 1b. Once the MTD was established, the participant cohort was expanded to a minimum of 10 participants. The MTD was confirmed by assessing DLTs during Cycle 1 and intolerable toxicities (i.e., not manageable with dose interruption and/or reduction) during Cycle 2 of therapy. Once the dose of lenvatinib/everolimus combination to be used in the succeeding Phase 2 part of the study was established, enrollment into Phase 2 was started. The RP2 dose was the same as the confirmed MTD and was used for the Phase 2 Treatment Arm A of this study.
Safety analysis set included all participants who received at least one dose of study treatment.
Posted
Number
mg/day
First dose of study drug (Cycle 1 Day 1) to end of Cycle 2 (1 cycle = 28 days/4 weeks)
ID
Title
Description
OG000
Phase 1b: Dose Escalation and MTD Expansion Cohorts
Oral everolimus (18 mg) and lenvatinib (5 mg) were taken once daily in the morning (consistently with or without food) with water. Any dietary habits around the time of study medication intake had to be kept as consistent as possible throughout the study.
Units
Counts
Participants
Primary
Phase 2: Progression-Free Survival (PFS)
PFS was defined as the time (in months) from the date of first dose of study drug to the first documentation of disease progression or death, whichever occurred first. Kaplan-Meier (K-M) estimates were used to estimate median PFS, presented with 2-sided 95% confidence intervals (CIs). Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease using computed tomography (CT) or magnetic resonance imaging (MRI) and scan acquisition techniques (including use or nonuse of intravenous (IV) contrast). Tumor response was determined at the site by the investigator and radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in the evaluation of the tumor assessment scans. The date of objective disease progression was defined as the earliest date of radiological disease progression. Participants removed from therapy due to clinical progression with no radiologic confirmation were censored at their last radiologic assessment date.
Full analysis set included all randomized participants.
Posted
Median
95% Confidence Interval
Months
Date of randomization into Phase 2 (Cycle 1 Day 1) to the date of first documentation of disease progression or death (whichever occurred first), assessed up to data cutoff date (13 Jun 2014), up to approximately 2 years and 3 months
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Secondary
Phase 2: Overall Survival (OS)
OS was defined as the time (in months) from the date of randomization until date of death from any cause. Median survival time was calculated using K-M estimate for each treatment arm and presented with 2-sided 95% CIs. Participants who were lost to follow-up or alive at the data cutoff date (10 Dec 2014) were censored at the date the participants were last known to be alive.
Full analysis set which included all randomized participants.
Posted
Median
95% Confidence Interval
Months
Randomization (Cycle 1 Day 1) until date of death from any cause, assessed up to the data cutoff date (10 Dec 2014), up to approximately 2 years and 9 months
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Secondary
Phase 2: Objective Response Rate (ORR)
The ORR was defined as the percentage of participants who had the best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator, using RECIST 1.1 in the evaluation of MRI or CT scans of targeted lesions. Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease). The BOR was defined as the best response recorded from the start of the study treatment until discontinuation from the study. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR was calculated with exact 95% CIs using the method of Clopper and Pearson.
Full analysis set which included all randomized participants.
Posted
Number
95% Confidence Interval
Percentage of participants
Randomization (Cycle 1 Day 1) until first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Secondary
Disease Control Rate (DCR)
The DCR was defined as the percentage of participants who had a BOR of CR or PR or SD (minimum duration from randomization to SD greater than or equal to 7 weeks). Assessments were performed every 8 weeks and were based on investigator review data using RECIST 1.1. The 95% CI was constructed using the method of Clopper and Pearson. DCR = CR + PR + SD greater than or equal to 7 weeks.
Full analysis set which included all randomized participants.
Posted
Number
95% Confidence Interval
Percentage of participants
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day withwater, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Secondary
Durable Stable Disease (SD) Rate
The durable SD rate was defined as the percentage of participants whose BOR was SD and the duration of SD was greater than or equal to 23 weeks. The durable SD was based on investigator review data using RECIST 1.1. The 95% CI was constructed using the method of Clopper and Pearson.
Full analysis set which included all randomized participants.
Posted
Number
95% Confidence Interval
Percentage of participants
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Secondary
Clinical Benefit Rate (CBR)
The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (duration of SD was greater than or equal to 23 weeks) and was based on investigator review data using RECIST 1.1. The BOR was defined as the best response recorded from the start of study treatment until discontinuation from the study. There was no requirement for confirmatory measurement of PR or CR to deem either one the BOR. The 95% CI was constructed using the method of Clopper and Pearson. CBR = CR + PR + SD greater than or equal to 23 weeks.
Full analysis set which included all randomized participants.
Posted
Number
95% Confidence Interval
Percentage of participants
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Secondary
Summary of Plasma Concentrations of Lenvatinib for Sparse Pharmacokinetic (PK) Sampling for Phase 1b and Phase 2
Blood samples were collected during the Randomization Phase. Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose). Plasma concentrations of lenvatinib were measured and concentration data were summarized. The summary statistics at time points with one or more below the limit of quantitation (BLQ) values were calculated by assigning zero for each BLQ value.
Pharmacokinetic analysis set included all participants who have received at least one dose of study drug (lenvatinib or everolimus) and have evaluable concentration data.
Posted
Geometric Mean
Standard Deviation
ng/mL
Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
ID
Title
Description
OG000
Cycle 1, Day 1 (0 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected immediately prior to study drug administration.
OG001
Cycle 1, Day 1 (2-8 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected 2 to 8 hours after study drug administration.
OG002
Cycle 2, Day 1 (0 Hours)
Secondary
Summary of Blood Concentrations of Everolimus for Sparse PK Sampling for Phase 1b and Phase 2
Blood samples were collected during the Randomization Phase. Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose). Whole blood concentrations of everolimus were measured and concentration data were summarized. The summary statistics at time points with one or more BLQ values were calculated by assigning zero for each BLQ value.
Pharmacokinetic analysis set included all participants who received at least one dose of study drug (lenvatinib or everolimus) and had evaluable concentration data.
Posted
Geometric Mean
Standard Deviation
ng/mL
Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
ID
Title
Description
OG000
Cycle 1, Day 1 (0 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected immediately prior to study drug administration.
OG001
Cycle 1, Day 1 (2-8 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected 2 to 8 hours after study drug administration.
OG002
Cycle 2, Day 1 (0 Hours)
Secondary
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC(0-24)) for Lenvatinib When Administered Alone or in Combination With Everolimus
Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling. Blood samples were analyzed for study drug using standardized methods. PK parameters for lenvatinib were derived from lenvatinib concentration data using non-compartmental methods. Data were compared via descriptive statistics between single agent and combination therapy.
Pharmacokinetic sub analysis set consisted of all participants who agreed to participate in the intensive PK sampling portion of Phase 2 of the study, had received at least 1 dose of study drug (lenvatinib or everolimus), and had evaluable concentration data.
Posted
Mean
Standard Deviation
ng·hr/mL
Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
ID
Title
Description
OG000
Phase 2: 18 mg Lenvatinib + 5 mg Everolimus
Oral lenvatinib (18mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
Secondary
Maximum Concentration (Cmax) of Lenvatinib in Plasma When Administered Alone or in Combination With Everolimus
Cmax for lenvatinib was defined as the maximum observed concentration of lenvatinib in plasma following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured plasma concentration-time curves.
PK sub analysis set
Posted
Mean
Standard Deviation
ng/mL
Phase 2: Cycle 1 Day 15
ID
Title
Description
OG000
Phase 2: 18 mg Lenvatinib + 5 mg Everolimus
Oral lenvatinib (18mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG001
Phase 2: 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Secondary
Time to Cmax (Tmax) for Lenvatinib When Administered Alone or in Combination With Everolimus
Tmax for lenvatinib was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach maximum concentration (Cmax) of lenvatinib in plasma.
PK sub analysis set
Posted
Median
Full Range
Hours
Phase 2: Cycle 1 Day 15
ID
Title
Description
OG000
Phase 2: 18 mg Lenvatinib + 5 mg Everolimus
Oral lenvatinib (18mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG001
Phase 2: 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Counts
Secondary
Area Under the Blood Concentration-Time Curve From 0 to 24 Hours for Everolimus When Administered Alone or in Combination With Lenvatinib
Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling. Blood samples were analyzed for study drug using standardized methods. PK parameters for everolimus were derived from everolimus concentration data using non-compartmental methods. Data were compared via descriptive statistics between single agent and combination therapy.
PK sub analysis set. n=8 for AUC(0-24)
Posted
Mean
Standard Deviation
ng·hr/mL
Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
ID
Title
Description
OG000
Phase 2: 18 mg Lenvatinib + 5 mg Everolimus
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG001
Phase 2: 10 mg Everolimus
Secondary
Maximum Concentration of Everolimus (Cmax) in Blood When Administered Alone or in Combination With Lenvatinib
Cmax for everolimus was defined as the maximum observed concentration of everolimus in blood following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured blood concentration-time curves.
PK sub analysis set
Posted
Mean
Standard Deviation
ng/mL
Phase 2: Cycle 1 Day 15
ID
Title
Description
OG000
Phase 2: 18 mg Lenvatinib + 5 mg Everolimus
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG001
Phase 2: 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Secondary
Time to Cmax (Tmax) for Everolimus When Administered Alone or in Combination With Lenvatinib
Tmax for everolimus was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach the maximum concentration (Cmax) of everolimus in blood.
PK sub analysis set
Posted
Median
Full Range
Hours
Phase 2: Cycle 1 Day 15
ID
Title
Description
OG000
Phase 2: 18 mg Lenvatinib + 5 mg Everolimus
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG001
Phase 2: 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Counts
Time Frame
Treatment-emergent adverse events (AEs) were collected and defined as those AEs that occurred after the first dose of study medication and up to 30 days after the last dose of study medication. AEs were collected for approximately 4 years.
Description
Safety analysis set included all participants who received at least one dose of study drug/s and had at least one postbaseline safety evaluation. AE severity was assessed using Common Terminology for Adverse Events (CTCAE). Serious AEs were followed until the event resolved or the event or sequelae stabilized.
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.
If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
43
51
30
51
51
51
EG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
40
52
28
52
51
52
EG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4 week) cycles.
45
50
21
50
50
50
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Cardiomyopathy
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG0030 affected0 at risk
EG0040 affected51 at risk
EG0050 affected52 at risk
EG0060 affected50 at risk
Myocardial Infarction
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Abdominal Pain
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Fatigue
General disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
General Physical Health Deterioration
General disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Non-Cardiac Chest Pain
General disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Cholangitis
Hepatobiliary disorders
MedDRA 19.1
Non-systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Lung Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Ejection Fraction Decreased
Investigations
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
White Blood Cell Count Decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Metastatic Pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Renal Failure Acute
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Pleural Effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Sideroblastic Anaemia
Blood and lymphatic system disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Acute Myocardial Infarction
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Cardiac Failure
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Cardiac Failure Congestive
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Vertigo Positional
Ear and labyrinth disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Inappropriate Antidiuretic Hormone Secretion
Endocrine disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Gastric Haemorrhage
Gastrointestinal disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Asthenia
General disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Chest Discomfort
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pain
General disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pyrexia
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Cholecystitis Acute
Hepatobiliary disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Drug Hypersensitivity
Immune system disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Appendicitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Appendicitis Perforated
Infections and infestations
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Bronchopneumonia
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Diabetic Foot Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Escherichia Sepsis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Infectious Pleural Effusion
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Lower Respiratory Tract Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Osteomyelitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Parotitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Rectal Abscess
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Sepsis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Joint Dislocation
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Spinal Compression Fracture
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Toxicity to Various Agents
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Bilirubin Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Creatinine Phosphokinase Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Body Temperature Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Electrocardiogram Repolarisation Abnormality
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Fibrin D Dimer Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Transaminases Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Decreased Appetite
Metabolism and nutrition disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Failure to Thrive
Metabolism and nutrition disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Glucose Tolerance Impaired
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Malnutrition
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Back Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Flank Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Haemarthrosis
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Musculoskeletal Chest Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Psoriatic Arthropathy
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Cerebral Haemorrhage
Nervous system disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Convulsion
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Haemorrhage Intracranial
Nervous system disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Headache
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Ischaemic Stroke
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Paresis
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Posterior Reversible Encephalopathy Syndrome
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Spinal Cord Compression
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Trigeminal Neuralgia
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Confusional State
Psychiatric disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Renal Impairment
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Benign Prostatic Hyperplasia
Reproductive system and breast disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Acute Respiratory Failure
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pulmonary Embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Deep Vein Thrombosis
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hot Flush
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Subclavian Vein Thrombosis
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Venous Thrombosis
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Lipase Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pathological Fracture
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Spinal Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Malignant Pleural Effusion
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Carotid Artery Occlusion
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 19.1
Non-systematic Assessment
EG0002 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG0030 affected0 at risk
EG0047 affected51 at risk
EG0053 affected52 at risk
EG00611 affected50 at risk
Haemorrhagic Disorder
Blood and lymphatic system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Angina Pectoris
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Aortic Valve Incompetence
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Coronary Artery Disease
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Coronary Artery Occlusion
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Mitral Valve Incompetence
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Ventricular Hypokinesia
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Ear Pain
Ear and labyrinth disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Inappropriate Antidiuretic Hormone Secretion
Endocrine disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Diplopia
Eye disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Eye Swelling
Eye disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Ocular Hyperaemia
Eye disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Vision Blurred
Eye disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Abdominal Pain
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Abdominal Pain Upper
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Anal Pruritus
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Anorectal Discomfort
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Aphthous Stomatitis
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0003 affected7 at risk
EG0014 affected11 at risk
EG0021 affected2 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0003 affected7 at risk
EG0017 affected11 at risk
EG0021 affected2 at risk
EG003
Dry Mouth
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0021 affected2 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0014 affected11 at risk
EG0020 affected2 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Gastric Haemorrhage
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Gastrooesophageal Reflux Disease
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Gingival Bleeding
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Glossitis
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Glossodynia
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Haemorrhoidal Haemorrhage
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Lip Discolouration
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0006 affected7 at risk
EG0016 affected11 at risk
EG0021 affected2 at risk
EG003
Oral Mucosal Blistering
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Oral Pain
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Paraesthesia Oral
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0004 affected7 at risk
EG0017 affected11 at risk
EG0022 affected2 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0005 affected7 at risk
EG0015 affected11 at risk
EG0021 affected2 at risk
EG003
Asthenia
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Chills
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Fatigue
General disorders
MedDRA 19.1
Systematic Assessment
EG0004 affected7 at risk
EG00111 affected11 at risk
EG0022 affected2 at risk
EG003
Gait Disturbance
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Localised Oedema
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Non-Cardiac Chest Pain
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Oedema Peripheral
General disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0016 affected11 at risk
EG0020 affected2 at risk
EG003
Pyrexia
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Dilatation Intrahepatic Duct Acquired
Hepatobiliary disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Infectious Pleural Effusion
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Influenza
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Lymph Gland Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Oral Herpes
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Osteomyelitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Paronychia
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Skin Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Urinary Tract Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Arthropod Bite
Injury, poisoning and procedural complications
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Periorbital Contusion
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Toxicity to Various Agents
Injury, poisoning and procedural complications
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Alanine Aminotransferase Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Amylase Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Aspartate Aminotransferase Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Alkaline Phosphatase Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Bilirubin Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Cholesterol Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Creatine Phosphokinase Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Glucose Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Phosphorus Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Potassium Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Triglycerides Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Cardiac Murmur
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Computerised Tomogram Thorax Abnormal
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Ejection Fraction Decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Electrocardiogram QT Prolonged
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Haemoglobin Decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Lipase Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Liver Function Test Abnormal
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Murphy's Sign Positive
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Platelet Count Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Protein Urine Present
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Transaminases Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Weight Decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0015 affected11 at risk
EG0020 affected2 at risk
EG003
White Blood Cell Count Decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
White Blood Cell Count Increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Decreased Appetite
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0003 affected7 at risk
EG0016 affected11 at risk
EG0021 affected2 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Failure to Thrive
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Hyperlipidaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hypernatraemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hypertriglyceridaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0017 affected11 at risk
EG0020 affected2 at risk
EG003
Hypophagia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 19.1
Non-systematic Assessment
EG0003 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hypovolaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Malnutrition
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Metabolic Acidosis
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0004 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Back Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0003 affected7 at risk
EG0014 affected11 at risk
EG0020 affected2 at risk
EG003
Flank Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Intervertebral Disc Protrusion
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Muscle Spasms
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Muscular Weakness
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Musculoskeletal Chest Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Musculoskeletal Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0003 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Neck Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Pain in Extremity
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0014 affected11 at risk
EG0020 affected2 at risk
EG003
Spinal Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Disturbance In Attention
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0015 affected11 at risk
EG0021 affected2 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Headache
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0004 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Hyperaesthesia
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0021 affected2 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0021 affected2 at risk
EG003
Peripheral Sensory Neuropathy
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Sensory Disturbance
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Sinus Headache
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Tremor
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0021 affected2 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Confusional State
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0010 affected11 at risk
EG0021 affected2 at risk
EG003
Depression
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0021 affected2 at risk
EG003
Nocturia
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0005 affected7 at risk
EG0016 affected11 at risk
EG0020 affected2 at risk
EG003
Renal Failure Acute
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Renal Failure Chronic
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Renal Mass
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Vaginal Haemorrhage
Reproductive system and breast disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0021 affected2 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0006 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0017 affected11 at risk
EG0021 affected2 at risk
EG003
Dyspnoea Exertional
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0015 affected11 at risk
EG0021 affected2 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Lung Infiltration
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0021 affected2 at risk
EG003
Nasal Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Oropharyngeal Pain
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Pleural Effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Productive Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Sinus Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Sputum Discoloured
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Upper-Airway Cough Syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Dermatitis Acneiform
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Dry Skin
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0003 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Ecchymosis
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Erythema Multiforme
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hyperkeratosis
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Night Sweats
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Palmar-Plantar Erythrodysaesthesia Syndrome
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Petechiae
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0002 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0003 affected7 at risk
EG0015 affected11 at risk
EG0021 affected2 at risk
EG003
Rash Erythematous
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Rash Macular
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Skin Mass
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Skin Ulcer
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Aortic Dilatation
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Deep Vein Thrombosis
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hypertension
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0005 affected7 at risk
EG0014 affected11 at risk
EG0020 affected2 at risk
EG003
Hypotension
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0013 affected11 at risk
EG0020 affected2 at risk
EG003
Abdominal Pain Lower
Gastrointestinal disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Anal Fissure
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Cheilitis
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Mouth Ulceration
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Influenza Like Illness
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pain
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Thyroid Stimulating Hormone Increased
Investigations
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Lower Respiratory Tract Infection
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Bone Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Groin Pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pain In Jaw
Musculoskeletal and connective tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Lethargy
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hot Flush
Vascular disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Onychoclasis
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Respiratory Tract Infection
Infections and infestations
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Gingivitis
Infections and infestations
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Blood Creatinine Increased
Investigations
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 19.1
Non-systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 19.1
Non-systematic Assessment
EG0001 affected7 at risk
EG0012 affected11 at risk
EG0020 affected2 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Abdominal Discomfort
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Abdominal Distension
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0021 affected2 at risk
EG003
Malaise
General disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Peripheral Swelling
General disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Left ventricular dysfunction
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected11 at risk
EG0020 affected2 at risk
EG003
Paranasal sinus discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected11 at risk
EG0020 affected2 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
Not provided
Results Disclosure Restriction on PI(s)?
No
Other Details
Not provided
Point of Contact
Title
Organization
Phone
Extension
Email
Eisai Medical Services
Eisai Medical Inc.
1-888-422-4743
ID
Term
D002292
Carcinoma, Renal Cell
Ancestor Terms
ID
Term
D000230
Adenocarcinoma
D002277
Carcinoma
D009375
Neoplasms, Glandular and Epithelial
D009370
Neoplasms by Histologic Type
D009369
Neoplasms
D007680
Kidney Neoplasms
D014571
Urologic Neoplasms
D014565
Urogenital Neoplasms
D009371
Neoplasms by Site
D052776
Female Urogenital Diseases
D005261
Female Urogenital Diseases and Pregnancy Complications
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
OG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG00451
OG00552
OG00650
Title
Denominators
Categories
Title
Measurements
OG00414.6(5.9 to 20.1)
OG0057.4(5.6 to 10.2)
OG0065.5(3.5 to 7.1)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG004
OG006
Null hypothesis of no difference in PFS was analyzed using the stratified log-rank test with hemoglobin (less than or equal to 13 g/dL vs greater than 13 g/dL for males; and less than or equal to 11.5 g/dL vs greater than 11.5 g/dL for females) and corrected serum calcium (greater than or equal to 10 mg/dL vs less than 10 mg/dL) as stratification factors. Each null hypothesis was tested at a nominal alpha=0.05.
Log Rank
=0.0005
Hazard Ratio (HR)
0.40
2-Sided
95
0.24
0.68
Hazard ratio between treatment groups and corresponding 95% CI was estimated using the stratified Cox regression model (stratified by hemoglobin and corrected serum calcium) with treatment as a factor.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
OG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG00451
OG00552
OG00650
Title
Denominators
Categories
Title
Measurements
OG00425.5(16.4 to NA)NA = not estimable
OG00519.1(13.6 to 26.2)
OG00615.4(11.8 to 19.6)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG004
OG006
Planned analyses were performed to test null hypothesis of treatment difference in OS at a nominal significance level of 0.05 (2-sided) using the stratified log-rank test using stratification factors.
Log Rank
=0.0242
Hazard Ratio (HR)
0.514
2-Sided
95
0.299
0.884
Hazard ratio between treatment groups and corresponding 95% CI was estimated using the stratified Cox regression model (stratified by hemoglobin and corrected serum calcium) with treatment as a factor.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
OG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG00451
OG00552
OG00650
Title
Denominators
Categories
Title
Measurements
OG00443.1(29.3 to 57.8)
OG00526.9(15.6 to 41.0)
OG0066.0(1.3 to 16.5)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG004
OG006
Fisher Exact
<0.0001
Analysis performed after database lock. P-value was based on the 2-sided Fisher's exact P-value.
Rate ratio
7.2
2-Sided
95
2.3
22.5
Rate ratio was based on the normal approximation.
Superiority or Other
OG005
OG006
Fisher Exact
0.0067
Analysis performed after database lock. P-value was based on the 2-sided Fisher's exact P-value.
Rate ratio
4.5
2-Sided
95
1.4
14.7
Superiority or Other
OG004
OG005
Fisher Exact
=0.1007
Analysis performed after database lock. P-value was based on the 2-sided Fisher's exact P-value.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
OG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
OG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.
If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
OG005
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
OG006
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4 week) cycles.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG00451
OG00552
OG00650
Title
Denominators
Categories
Title
Measurements
OG00468.6(54.1 to 80.9)
OG00565.4(50.9 to 78.0)
OG00642.0(28.2 to 56.8)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected immediately prior to study drug administration.
OG003
Cycle 2, Day 1 (2-8 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected 2 to 8 hours after study drug administration.
OG004
Cycle 3, Day 1 (0 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected immediately prior to study drug administration.
OG005
Cycle 3, Day 1 (2-8 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected 2 to 8 hours after study drug administration.
Units
Counts
Participants
OG00057
OG00155
OG00245
OG00341
OG00442
OG00540
Title
Denominators
Categories
Title
Measurements
OG0005.6± 29.8
OG001197± 140
OG00266.9± 52.7
OG003237± 154
OG00437.0± 35.5
OG005180± 118
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected immediately prior to study drug administration.
OG003
Cycle 2, Day 1 (2-8 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected 2 to 8 hours after study drug administration.
OG004
Cycle 3, Day 1 (0 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected immediately prior to study drug administration.
OG005
Cycle 3, Day 1 (2-8 Hours)
Lenvatinib (18 mg) and everolimus (5 mg) were administered as described previously. Blood samples were collected 2 to 8 hours after study drug administration.
Units
Counts
Participants
OG00037
OG00135
OG00229
OG00328
OG00427
OG00525
Title
Denominators
Categories
Title
Measurements
OG0000.0± 0.00
OG00119.4± 9.16
OG00210.0± 7.28
OG00324.3± 14.2
OG0046.8± 6.06
OG00526.4± 14.8
OG001
Phase 2: 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
Units
Counts
Participants
OG0008
OG0019
Title
Denominators
Categories
Title
Measurements
OG0003185± 1030
OG0015252± 2717
Counts
Participants
OG0008
OG0019
Title
Denominators
Categories
Title
Measurements
OG000327± 179
OG001403± 165
Participants
OG0008
OG0019
Title
Denominators
Categories
Title
Measurements
OG0002.0(2.0 to 8.2)
OG0014.0(0.5 to 8.0)
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.