Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| JHOC-J06131 | |||
| GENETECH-SHH3925g |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | OTHER |
RATIONALE: Drugs used in chemotherapy, such as GDC-0449, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of GDC-0449 in treating patients with locally advanced or metastatic solid tumors.
OBJECTIVES:
Primary
Secondary
Tertiary
OUTLINE: This is a multicenter study.
Patients receive oral systemic Hedgehog antagonist GDC-0449 once on day 1 and then once or twice daily beginning on day 8 and continuing for up to 49 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo plasma, urine, and hair sample collection and skin punch biopsies periodically for pharmacokinetic and pharmacodynamic analyses. The plasma and urine samples are analyzed separately using liquid chromatography/tandem mass spectrometry-based methods. Ex vivo plasma protein binding of GDC-0449 is assayed using an equilibrium dialysis approach. Expression levels of Gli1 and other Hedgehog target genes in hair follicle samples and/or tumor tissue are measured at the RNA level using qRT-PCR.
After completion of study therapy, patients are followed at 21 days.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stage 1: GDC-0449 (150 mg) | Experimental | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 milligram (mg) on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST v1.0), maximum benefit, or intolerability. |
|
| Stage 1: GDC-0449 (270 mg) | Experimental | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
|
| Stage 1: GDC-0449 (540 mg) | Experimental | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
|
| Stage 2: BCC [GDC-0449 (150 mg)] | Experimental | Participants with basal cell carcinoma (BCC) received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GDC-0449 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | A DLT was defined as any Grade 3 or 4 hematologic or major organ toxicity as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) that occurred during the first 35 days after the initiation of study drug (Days 1-35) and was attributable to GDC-0449. | Up to Week 6 |
| Maximum Observed Plasma Concentration (Cmax) After a Single Dose of GDC-0449 | Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and pharmacodynamic (PD) data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial. | -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and - 5 minutes (pre-dose) on Day 8 |
| Cmax After Multiple Doses of GDC-0449 | Cmax was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve. | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
| Time to Maximum Plasma Concentration (Tmax) After a Single Dose of GDC-0449 | Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and PD data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial. | -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and - 5 minutes (pre-dose) on Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With a Greater Than (>) 2-Fold Down-Modulation of GLI1 Expression in Skin Biopsy-Derived or Hair Follicle-Derived Messenger Ribonucleic Acid (mRNA) | Ribonucleic acid (RNA) was extracted from biopsy specimens of noninvolved skin or hair follicles at baseline and at 7 and 21 days after the start of daily drug therapy. Control mRNA was obtained from formalin-fixed, paraffin-embedded samples of normal skin and hair follicles from participants who were not enrolled in the study. |
Not provided
DISEASE CHARACTERISTICS:
Histologically confirmed locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists
Progressed after first-line and second-line therapy (if there is a second-line therapy that has been shown to provide clinical benefit)
Evaluable disease by physical examination, imaging, and/or one of the following:
No CNS cancer, either primary lesions or metastatic disease, as the current malignancy
No pleural effusions, ascites, or leptomeningeal disease as the only manifestation of the current malignancy
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Granulocyte count ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Hemoglobin ≥ 9 g/dL
Serum bilirubin normal
Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN) (≤ 4 times ULN for patients with liver or bone metastases)
AST and ALT ≤ 1.5 times ULN (≤ 5 times the ULN for patients with liver metastases)
Serum creatinine ≤ 1.5 mg/dL
INR < 1.3
aPTT ≤ 1.5 times ULN
Fasting total serum cholesterol ≤ 220 mg/dL (without cholesterol-lowering drugs)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Able and willing to swallow pills
No malabsorption syndrome or other condition that would interfere with enteral absorption
No history of significant atherosclerotic disease, including the following:
No history of congestive heart failure or ventricular arrhythmia requiring medication
No congenital long QT syndrome
No baseline QTc intervals > 0.47 seconds on two of three baseline 12-lead ECGs recorded during the screening period
No active infection requiring intravenous antibiotics
No known HIV infection
No uncontrolled hypocalcemia, hypomagnesemia, or hypokalemia, defined as less than the lower limit of normal for the institution despite adequate electrolyte supplementation
No history of clinically important liver disease, including cirrhosis or viral or other hepatitis
No current alcohol abuse
No significant traumatic injury within the past 3 weeks
No other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the study results or renders the patient at high risk from treatment complications
PRIOR CONCURRENT THERAPY:
At least 4 weeks since prior chemotherapy, investigational therapy, radiotherapy, or major surgical procedure and recovered
No concurrent medications with narrow therapeutic indices that are cytochrome P450 substrates (warfarin sodium [Coumadin®])
No concurrent medications known to prolong the QT interval, including any of the following:
No concurrent medications that may interfere with the metabolism of GDC-0449 (e.g., ketoconazole)
No concurrent grapefruit juice
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23342272 | Derived | Thacker CA, Weiss GJ, Tibes R, Blaydorn L, Downhour M, White E, Baldwin J, Hoff DD, Korn RL. 18-FDG PET/CT assessment of basal cell carcinoma with vismodegib. Cancer Med. 2012 Oct;1(2):230-6. doi: 10.1002/cam4.33. Epub 2012 Sep 17. | |
| 19726763 | Derived | Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72. doi: 10.1056/NEJMoa0905360. Epub 2009 Sep 2. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Stage 1: GDC-0449 (150 mg) | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 milligram (mg) on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST v1.0), maximum benefit, or intolerability. |
| FG001 | Stage 1: GDC-0449 (270 mg) | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
| FG002 | Stage 1: GDC-0449 (540 mg) | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
| FG003 | Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] | Participants with basal cell carcinoma (BCC) received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| FG004 | Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] | Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| FG005 | Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] | Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| FG006 | Stage 2: New Formulation [GDC-0449 (150 mg )] | Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1: Dose Escalation |
|
| ||||||||||||||||||
| Stage 2: Expanded Cohort |
|
Safety-evaluable population included all participants who received any amount of GDC-0449.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Stage 1: GDC-0449 (150 mg) | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | A DLT was defined as any Grade 3 or 4 hematologic or major organ toxicity as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) that occurred during the first 35 days after the initiation of study drug (Days 1-35) and was attributable to GDC-0449. | Safety-evaluable population. | Posted | Number | percentage of participants | Up to Week 6 |
|
From Screening up to 28 days after the last dose of GDC-0449 (Week 116).
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stage 1: GDC-0449 (150 mg) | Participants received single dose of GDC-0449 hard gelatin capsules at 150 mg on Day 1, thereafter Day 8 received daily until disease progression, maximum benefit, or intolerability. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| C538724 | HhAntag691 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Stage 2: BCC [GDC-0449 (270 mg)] | Experimental | Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
|
| Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] | Experimental | Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
|
| Stage 2: New Formulation [GDC-0449 (150 mg )] | Experimental | Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
|
|
| Tmax After Multiple Doses of GDC-0449 | Tmax was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve. | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
| Average Plasma Concentration at Steady State (Css, Avg) After Multiple Doses of GDC-0449 | Steady state GDC-0449 plasma concentrations (Css) were calculated as an average of plasma concentrations from Study Day 21 (Stage 2) or Study Day 28 (Stage 1) onward. | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
| Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) After a Single Dose of GDC-0449 | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and PD data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial. | -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and - 5 minutes (pre-dose) on Day 8 |
| AUC0-24 After Multiple Doses of GDC-0449 | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUC was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve. | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
| Accumulation Index (AI) After Multiple Doses of GDC-0449 | AI was calculated using the formula [AI = AUC(0-24) on Day 15/AUC(0-24) on Day 1]. AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AI was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve. | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
| Baseline up to Day 29 |
| Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR): All Participants | BOR was defined as the best objective response (complete or partial response determined by two consecutive investigator assessments which were at least 28 days apart) observed during the treatment period according to RECIST v1.0. CR: disappearance of all target lesions (TLs), with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 millimeters (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of TLs, taking as reference the baseline (BL) sum diameters. | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
| Percentage of Participants With a BOR of CR or PR: Participants With Basal Cell Carcinoma | BOR was defined as the best objective response observed during the treatment period according to RECIST v1.0. CR: disappearance of all TLs, with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in the sum of diameters of TLs, taking as reference the BL sum diameters. | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
| Duration of Objective Response: All Participants | Duration of response during first line therapy is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy. | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
| Duration of Objective Response: Participants With BCC | Duration of response during first line therapy is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy. | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
| Progression-Free Survival (PFS): All Participants | PFS was defined as the time from first dose of GDC-0449 to documented disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using RECIST v1.0) or death from any cause within 30 days of the last dose of GDC-0449, whichever occurred first. | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
| PFS: Participants With BCC | PFS was defined as the time from first dose of GDC-0449 to documented disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using RECIST v1.0) or death from any cause within 30 days of the last dose of GDC-0449, whichever occurred first. | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Stage 1: GDC-0449 (270 mg) |
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
| BG002 | Stage 1: GDC-0449 (540 mg) | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
| BG003 | Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] | Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| BG004 | Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] | Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| BG005 | Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] | Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| BG006 | Stage 2: New Formulation [GDC-0449 (150 mg )] | Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability |
| BG007 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 |
| Stage 1: GDC-0449 (270 mg) |
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
| OG002 | Stage 1: GDC-0449 (540 mg) | Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability. |
| OG003 | Stage 2: Basal Cell Carcinoma (GDC-0449 [150 mg]) | Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| OG004 | Stage 2: Basal Cell Carcinoma (GDC-0449 [270 mg]) | Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| OG005 | Stage 2:Safety Expansion Cohort (GDC-0449 [150 mg]) | Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
| OG006 | Stage 2: New Formulation (GDC-0449 [150 mg]) | Participants received GDC-0449 Phase II drug product as 150-mg hard gelatin capsules daily, orally, starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. |
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) After a Single Dose of GDC-0449 | Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and pharmacodynamic (PD) data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial. | Pharmacokinetic (PK)-evaluable population included participants who had at least Day 1 PK samples available. | Posted | Mean | Standard Deviation | micromolar (mcM) | -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and - 5 minutes (pre-dose) on Day 8 |
|
|
|
| Primary | Cmax After Multiple Doses of GDC-0449 | Cmax was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve. | Cmax was not reported as there were <50% participants with extensive PK sampling and the PK profiles were flat over 24 hours at steady state which did not allow estimation of Cmax. | Posted | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
|
|
| Primary | Time to Maximum Plasma Concentration (Tmax) After a Single Dose of GDC-0449 | Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and PD data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial. | PK-evaluable population. | Posted | Median | Full Range | days | -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and - 5 minutes (pre-dose) on Day 8 |
|
|
|
| Primary | Tmax After Multiple Doses of GDC-0449 | Tmax was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve. | Cmax was not reported as there were <50% participants with extensive PK sampling and the PK profiles were flat over 24 hours at steady state which did not allow estimation of Cmax, and as Tmax was related to Cmax, it was also not estimated. | Posted | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
|
|
| Primary | Average Plasma Concentration at Steady State (Css, Avg) After Multiple Doses of GDC-0449 | Steady state GDC-0449 plasma concentrations (Css) were calculated as an average of plasma concentrations from Study Day 21 (Stage 2) or Study Day 28 (Stage 1) onward. | PK-evaluable population. Here "number of participants analyzed" = participants evaluable for this measure. | Posted | Mean | Standard Deviation | mcM | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) After a Single Dose of GDC-0449 | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and PD data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial. | PK-evaluable population. | Posted | Mean | Standard Deviation | mcM*day | -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and - 5 minutes (pre-dose) on Day 8 |
|
|
|
| Primary | AUC0-24 After Multiple Doses of GDC-0449 | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUC was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve. | AUC0-24 was not reported as there were <50% participants with extensive PK sampling and the PK profiles were flat over 24 hours at steady state which did not allow estimation of AUC0-24. | Posted | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
|
|
| Primary | Accumulation Index (AI) After Multiple Doses of GDC-0449 | AI was calculated using the formula [AI = AUC(0-24) on Day 15/AUC(0-24) on Day 1]. AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AI was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve. | AI was not reported as there were <50% participants with extensive PK sampling and the PK profiles were flat over 24 hours at steady state which did not allow estimation of AI. | Posted | -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years |
|
|
| Secondary | Percentage of Participants With a Greater Than (>) 2-Fold Down-Modulation of GLI1 Expression in Skin Biopsy-Derived or Hair Follicle-Derived Messenger Ribonucleic Acid (mRNA) | Ribonucleic acid (RNA) was extracted from biopsy specimens of noninvolved skin or hair follicles at baseline and at 7 and 21 days after the start of daily drug therapy. Control mRNA was obtained from formalin-fixed, paraffin-embedded samples of normal skin and hair follicles from participants who were not enrolled in the study. | Pharmacodynamic-evaluable population included participants who had hair and/or skin samples available from Day 1 and at least one post-baseline sample while on study treatment. Here "number of participants analyzed" = participants evaluable for this measure and "n"= participants evaluable for the specific category. | Posted | Number | percentage of participants | Baseline up to Day 29 |
|
|
|
| Secondary | Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR): All Participants | BOR was defined as the best objective response (complete or partial response determined by two consecutive investigator assessments which were at least 28 days apart) observed during the treatment period according to RECIST v1.0. CR: disappearance of all target lesions (TLs), with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 millimeters (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of TLs, taking as reference the baseline (BL) sum diameters. | Efficacy-evaluable population were those with measurable disease at baseline and who received at least 1 dose of GDC-0449 and either had a post-baseline tumor assessment or progressed before any tumor assessment. | Posted | Number | percentage of participants | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
|
|
|
| Secondary | Percentage of Participants With a BOR of CR or PR: Participants With Basal Cell Carcinoma | BOR was defined as the best objective response observed during the treatment period according to RECIST v1.0. CR: disappearance of all TLs, with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in the sum of diameters of TLs, taking as reference the BL sum diameters. | Efficacy-evaluable population; only participants with BCC were included in the analysis. | Posted | Number | percentage of participants | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
|
|
|
| Secondary | Duration of Objective Response: All Participants | Duration of response during first line therapy is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy. | Efficacy-evaluable population; only participants who achieved a best overall response of CR or PR were included in the analysis. | Posted | Median | 95% Confidence Interval | months | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
|
|
|
| Secondary | Duration of Objective Response: Participants With BCC | Duration of response during first line therapy is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy. | Efficacy-evaluable participants; only participants with BCC who achieved a best overall response of CR or PR were included in the analysis. | Posted | Median | Full Range | months | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
|
|
|
| Secondary | Progression-Free Survival (PFS): All Participants | PFS was defined as the time from first dose of GDC-0449 to documented disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using RECIST v1.0) or death from any cause within 30 days of the last dose of GDC-0449, whichever occurred first. | Efficacy-evaluable population. Number of participants censored for Stage 1 150 mg, 270 mg, and 540 mg were 1, 2, and 1 subjects, respectively and for Stage 2 BCC 150 mg, 270 mg, Stage 2 Safety Expansion Cohort 150 mg, and Stage 2 New Formulation 150 mg were 2, 6, 1, and 6 subjects, respectively. | Posted | Median | 95% Confidence Interval | months | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
|
|
|
| Secondary | PFS: Participants With BCC | PFS was defined as the time from first dose of GDC-0449 to documented disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using RECIST v1.0) or death from any cause within 30 days of the last dose of GDC-0449, whichever occurred first. | Efficacy-evaluable population; only participants with BCC were included in the analysis. Number of participants censored for Stage 1+Stage 2 150 mg, and Stage 1+Stage 2 270 mg were 8 and 7 subjects, respectively, and no subject censored from Stage 1 540 mg group. | Posted | Median | 95% Confidence Interval | months | Screening, at Week 8 thereafter every 8 weeks, up to Week 116 |
|
|
|
| 3 |
| 7 |
| 7 |
| 7 |
| EG001 | Stage 1: GDC-0449 (270 mg) | Stage 1: GDC-0449 (270 mg) Participants received single dose of GDC-0449 hard gelatin capsules at 270 mg on Day 1, thereafter Day 8 received daily dose until disease progression, maximum benefit, or intolerability. | 2 | 9 | 9 | 9 |
| EG002 | Stage 1: GDC-0449 (540 mg) | Participants received single dose of GDC-0449 hard gelatin capsules at 540 mg on Day 1, thereafter Day 8 received daily dose until disease progression, maximum benefit, or intolerability. | 1 | 4 | 4 | 4 |
| EG003 | Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] | Participants with basal cell carcinoma (BCC) received daily dose of GDC-0449 hard gelatin capsules at 150 mg on Day 1 until disease progression, maximum benefit, or intolerability. | 2 | 6 | 6 | 6 |
| EG004 | Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] | Participants with basal cell carcinoma (BCC) received daily dose of GDC-0449 hard gelatin capsules at 270 mg on Day 1 until disease progression, maximum benefit, or intolerability. | 4 | 14 | 14 | 14 |
| EG005 | Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] | Participants with tolerable safety, pharmacokinetic and pharmacodynamic data from Stage 1 received daily dose of GDC-0449 hard gelatin capsules at 150 mg on Day 1 until disease progression, maximum benefit, or intolerability. | 4 | 12 | 12 | 12 |
| EG006 | Stage 2: New Formulation [GDC-0449 (150 mg )] | Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. | 4 | 16 | 16 | 16 |
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Duodenal ulcer | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pancreatic carcinoma metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Adenocarcinoma pancreas | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Chondrosarcoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Paranoia | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal rigidity | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Duodenal ulcer | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dyschezia | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Faecal incontinence | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Gastric disorder | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Glossodynia | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperchlorhydria | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Lip ulceration | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Mucous stools | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oral cavity fistula | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oral mucosal blistering | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Tongue ulceration | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Tooth loss | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oedema | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Facial pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Axillary pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Catheter site related reaction | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Feeling cold | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Feeling hot | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Feeling jittery | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Puncture site haemorrhage | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sensation of foreign body | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Unevaluable event | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Ageusia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Anosmia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Amimia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Carotid artery stenosis | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dyskinesia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperaesthesia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypogeusia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Paresis cranial nerve | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Parosmia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Phantom pain | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sensory disturbance | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Tongue paralysis | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Trigeminal neuralgia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Viith nerve paralysis | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Madarosis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Actinic elastosis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Campbell de morgan spots | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| hair colour changes | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Nail ridging | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin tightness | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Salt craving | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hydrothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oropharyngeal swelling | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Wound infection staphylococcal | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Wound infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Abscess limb | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Catheter site infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Infected cyst | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Lobar pneumonia | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Localised infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Onychomycosis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Oral fungal infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Postoperative wound infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Rash pustular | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood chloride decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Weight increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood urine | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood urine present | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Brain natriuretic peptide increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Carbohydrate antigen 19-9 increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Electrocardiogram change | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Metamyelocyte percentage increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Myelocyte percentage increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abnormal dreams | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Stress | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Raynaud's phenomenon | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Arcus lipoides | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Eye discharge | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Keratitis | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pterygium | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Urinary hesitation | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Renal pain | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Urine flow decreased | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Wound secretion | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Corneal abrasion | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Muscle rupture | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Wound complication | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Auricular swelling | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Cerumen impaction | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dysacusis | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Ear canal stenosis | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Ear haemorrhage | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperacusis | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Cardiac flutter | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin neoplasm bleeding | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Amenorrhoea | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Breast swelling | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Menstruation irregular | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Phase II |
|
| Phase II |
|
| Phase II |
|