A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01107418
Collaborator
(none)
52
13
4
33.1
4
0.1
Study Details
Study Description
Brief Summary
This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 [RG7204; PLEXXIKON; PLX4032] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is <100 patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
52 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Randomized, Open-label, Multi-center, Multiple Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO5185426 Administered as 240 mg Tablets to Previously Treated BRAF V600E Positive Metastatic Melanoma Patients
Study Start Date
:
May 1, 2010
Actual Primary Completion Date
:
Feb 1, 2013
Actual Study Completion Date
:
Feb 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: RO5185426
960 mg orally twice daily, from day 22 onward
Drug: RO5185426
dosage a) orally twice daily, days 1-15 (morning dose)
|
| Experimental: 2
|
Drug: RO5185426
dosage b) orally twice daily, days 1-15 (morning dose)
Drug: RO5185426
960 mg orally twice daily, from day 22 onward
|
| Experimental: 3
|
Drug: RO5185426
dosage c) orally twice daily, days 1-15 (morning dose)
Drug: RO5185426
960 mg orally twice daily, from day 22 onward
|
| Experimental: 4
|
Drug: RO5185426
dosage d) orally twice daily, days 1-15 (morning dose)
Drug: RO5185426
960 mg orally twice daily, from day 22 onward
|
Outcome Measures
Primary Outcome Measures
- Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1 [Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1]
- Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1 [Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1]
- Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1 [Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1]
- Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1 [Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1]
- Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9 [Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9]
- Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9 [Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9]
- Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9 [Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9]
- Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15 [Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15]
- Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15 [Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15]
- Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15 [Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15]
- Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 [Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15]
- Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15 [Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15]
- Apparent Clearance (CL/F) of Vemurafenib on Day 15 [Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
- Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15 [Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15]
Time measured for vemurafenib plasma concentrations to decrease by one-half (t1/2) was calculated as 0.693 divided by apparent first-order terminal elimination rate constant (0.693/kel).
- Accumulation Ratio of Vemurafenib on Day 15 [Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15]
Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.
Secondary Outcome Measures
- Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) [Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)]
Confirmed best overall response was defined as having best objective response as CR or PR, as assessed by investigator and confirmed at least 28 days after initial response. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) were required to demonstrate a reduction to normal (short axis less than [<] 10 millimeters [mm]). PR was defined as a 30 percent (%) decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of confirmed CR or PR are reported.
- Overall Survival (OS) [Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)]
OS was defined as the time, in months, from the date of the first study drug administration to the date of death, regardless of the cause of death.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
adult patients, >/=18 years of age
-
histologically confirmed metastatic melanoma, stage IIIc or IV (AJCC)
-
failure of at least one prior standard of care regimen
-
positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)
-
ECOG performance status 0 or 1
-
adequate hematologic, renal and liver function
Exclusion Criteria:
-
active CNS lesions on CT/MRI within 28 days prior to enrollment
-
history of spinal cord compression o carcinomatous meningitis
-
anticipated or ongoing anti-cancer therapies other than those administered in this study
-
previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
-
severe cardiovascular disease within 6 months prior to study
-
previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | La Jolla | California | United States | 92093 | |
| 2 | San Francisco | California | United States | 94115 | |
| 3 | Stanford | California | United States | 94305 | |
| 4 | New Haven | Connecticut | United States | 06510-3289 | |
| 5 | Chicago | Illinois | United States | 60637 | |
| 6 | Park Ridge | Illinois | United States | 60068 | |
| 7 | Sioux City | Iowa | United States | 51101 | |
| 8 | Omaha | Nebraska | United States | 68114 | |
| 9 | Columbus | Ohio | United States | 43219 | |
| 10 | East Providence | Rhode Island | United States | 02915 | |
| 11 | Charlottesville | Virginia | United States | 22908 | |
| 12 | Adelaide | South Australia | Australia | 5000 | |
| 13 | Melbourne | Victoria | Australia | 3181 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01107418
Other Study ID Numbers:
- NP25163
First Posted:
Apr 21, 2010
Last Update Posted:
Aug 26, 2015
Last Verified:
Jul 1, 2015
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Vemurafenib - All Cohorts |
|---|---|
| Arm/Group Description | Participants received vemurafenib (RO5185426) film-coated tablets, orally, twice daily at doses of 240, 480, 720, or 960 milligrams (mg) on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Period Title: Overall Study | |
| STARTED | 52 |
| COMPLETED | 0 |
| NOT COMPLETED | 52 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Total of all reporting groups |
| Overall Participants | 12 | 12 | 12 | 16 | 52 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
52.0
(15.06)
|
46.3
(10.58)
|
54.3
(10.70)
|
50.5
(11.91)
|
50.8
(12.14)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
5
41.7%
|
7
58.3%
|
6
50%
|
8
50%
|
26
50%
|
| Male |
7
58.3%
|
5
41.7%
|
6
50%
|
8
50%
|
26
50%
|
Outcome Measures
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) population included all participants who provided essential PK data up to and including the pre-dose PK sample taken on Cycle 1, Day 22, without major protocol violation. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 12 | 12 | 12 | 16 |
| Mean (Standard Deviation) [micrograms*hour/milliliter (mcg*h/mL)] |
8.3
(6.13)
|
13.8
(7.72)
|
21.9
(12.97)
|
27.0
(18.87)
|
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 11 | 12 | 9 | 16 |
| Mean (Standard Deviation) [mcg*h/mL] |
40.9
(23.43)
|
62.4
(35.71)
|
111.6
(34.22)
|
130.6
(71.78)
|
| Title | Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 12 | 12 | 12 | 16 |
| Mean (Standard Deviation) [micrograms/milliliter (mcg/mL)] |
1.9
(1.66)
|
2.6
(1.56)
|
4.4
(1.98)
|
4.8
(3.34)
|
| Title | Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 12 | 12 | 12 | 16 |
| Median (Full Range) [hours] |
4.0
|
4.0
|
5.0
|
5.0
|
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 11 | 11 | 9 | 12 |
| Mean (Standard Deviation) [mcg*h/mL] |
102.1
(41.37)
|
180.0
(84.23)
|
301.2
(108.67)
|
329.0
(108.85)
|
| Title | Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 11 | 11 | 9 | 12 |
| Mean (Standard Deviation) [mcg/mL] |
15.4
(5.84)
|
28.9
(16.95)
|
45.9
(14.44)
|
53.2
(19.08)
|
| Title | Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 11 | 11 | 9 | 12 |
| Median (Full Range) [hours] |
2.0
|
2.0
|
0.0
|
1.8
|
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 10 | 9 | 9 | 11 |
| Mean (Standard Deviation) [mcg*h/mL] |
117.8
(50.52)
|
233.8
(106.93)
|
343.3
(151.23)
|
392.2
(126.37)
|
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 10 | 10 | 9 | 11 |
| Mean (Standard Deviation) [mcg*h/mL] |
317.7
(133.34)
|
598.8
(297.44)
|
1003.7
(441.36)
|
1126.0
(423.01)
|
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 10 | 8 | 9 | 11 |
| Mean (Standard Deviation) [mcg*h/mL] |
920.3
(538.35)
|
2243.5
(1336.15)
|
3127.1
(1789.97)
|
3530.3
(1811.43)
|
| Title | Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 10 | 9 | 9 | 11 |
| Mean (Standard Deviation) [mcg/mL] |
17.2
(7.43)
|
35.4
(17.44)
|
52.7
(22.40)
|
61.4
(22.76)
|
| Title | Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 10 | 9 | 9 | 11 |
| Median (Full Range) [hours] |
4.0
|
2.3
|
2.0
|
2.0
|
| Title | Apparent Clearance (CL/F) of Vemurafenib on Day 15 |
|---|---|
| Description | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 10 | 8 | 9 | 11 |
| Mean (Standard Deviation) [liters/hour (L/h)] |
0.3
(0.13)
|
0.8
(1.45)
|
0.4
(0.28)
|
0.3
(0.19)
|
| Title | Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15 |
|---|---|
| Description | Time measured for vemurafenib plasma concentrations to decrease by one-half (t1/2) was calculated as 0.693 divided by apparent first-order terminal elimination rate constant (0.693/kel). |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 10 | 10 | 9 | 11 |
| Mean (Standard Deviation) [hours] |
31.5
(19.05)
|
38.4
(24.18)
|
34.9
(19.48)
|
34.1
(19.66)
|
| Title | Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) |
|---|---|
| Description | Confirmed best overall response was defined as having best objective response as CR or PR, as assessed by investigator and confirmed at least 28 days after initial response. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) were required to demonstrate a reduction to normal (short axis less than [<] 10 millimeters [mm]). PR was defined as a 30 percent (%) decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of confirmed CR or PR are reported. |
| Time Frame | Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy population: all enrolled participants who received at least one dose of vemurafenib, had measurable target lesions at baseline based on RECIST 1.1 criteria, had no major protocol violations of inclusion/exclusion criteria, and had no other violations affecting efficacy assessments. |
| Arm/Group Title | Vemurafenib - All Cohorts |
|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablets, orally, twice daily at doses of 240, 480, 720, or 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 49 |
| Number [percentage of participants] |
49
408.3%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time, in months, from the date of the first study drug administration to the date of death, regardless of the cause of death. |
| Time Frame | Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for this outcome measure was not collected as the outcome was removed as per changes in planned analysis (protocol amendment). |
| Arm/Group Title | Vemurafenib - All Cohorts |
|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablets, orally, twice daily at doses of 240, 480, 720, or 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 0 |
| Title | Accumulation Ratio of Vemurafenib on Day 15 |
|---|---|
| Description | Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1. |
| Time Frame | Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population. Here, number of participants analyzed signifies participants evaluable for this outcome. |
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. |
| Measure Participants | 10 | 9 | 9 | 11 |
| Mean (Standard Deviation) [ratio] |
24.9
(29.4)
|
23.3
(16.0)
|
18.8
(12.4)
|
23.2
(16.5)
|
Adverse Events
| Time Frame | Up to approximately 3 years | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg | ||||
| Arm/Group Description | Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal. | ||||
All Cause Mortality |
||||||||
| Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/12 (25%) | 3/12 (25%) | 8/12 (66.7%) | 7/16 (43.8%) | ||||
| Cardiac disorders | ||||||||
| Pericarditis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Ascites | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Nausea | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Rectal haemorrhage | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Small intestinal obstruction | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| General disorders | ||||||||
| Pyrexia | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Pain | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Hepatobiliary disorders | ||||||||
| Jaundice cholestatic | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Infections and infestations | ||||||||
| Device related infection | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Femur fracture | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hyponatraemia | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Musculoskeletal chest pain | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Pathological fracture | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Squamous cell carcinoma of skin | 1/12 (8.3%) | 2/12 (16.7%) | 2/12 (16.7%) | 2/16 (12.5%) | ||||
| Keratoacanthoma | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Squamous cell carcinoma of the oral cavity | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Pleural effusion | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Pleuritic pain | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Shock | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Cohort 1 - Vemurafenib 240 mg | Cohort 2 - Vemurafenib 480 mg | Cohort 3 - Vemurafenib 720 mg | Cohort 4 - Vemurafenib 960 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/12 (100%) | 12/12 (100%) | 12/12 (100%) | 16/16 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/12 (16.7%) | 0/12 (0%) | 1/12 (8.3%) | 3/16 (18.8%) | ||||
| Leukocytosis | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Leukopenia | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Lymphadenopathy | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Palpitations | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Sinus tachycardia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Tachycardia | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 4/16 (25%) | ||||
| Congenital, familial and genetic disorders | ||||||||
| Dermoid cyst | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Keratosis follicular | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Porokeratosis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Ear and labyrinth disorders | ||||||||
| Deafness unilateral | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Hypoacusis | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Endocrine disorders | ||||||||
| Cushingoid | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Eye disorders | ||||||||
| Binocular eye movement disorder | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Conjunctivitis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 2/16 (12.5%) | ||||
| Diplopia | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Dry eye | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Episcleritis | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Eye irritation | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Eye swelling | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Eyelid irritation | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Eyelid ptosis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Lacrimation increased | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Ocular discomfort | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Ocular hyperaemia | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Periorbital oedema | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Pupils unequal | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Retinal disorder | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Visual acuity reduced | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Visual impairment | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Abdominal distension | 1/12 (8.3%) | 1/12 (8.3%) | 2/12 (16.7%) | 0/16 (0%) | ||||
| Abdominal pain | 2/12 (16.7%) | 2/12 (16.7%) | 2/12 (16.7%) | 0/16 (0%) | ||||
| Abdominal pain lower | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Abdominal pain upper | 1/12 (8.3%) | 1/12 (8.3%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Ascites | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Constipation | 3/12 (25%) | 6/12 (50%) | 2/12 (16.7%) | 4/16 (25%) | ||||
| Diarrhoea | 4/12 (33.3%) | 5/12 (41.7%) | 5/12 (41.7%) | 6/16 (37.5%) | ||||
| Dry mouth | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Dyspepsia | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Dysphagia | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Faecal incontinence | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Flatulence | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Gastrooesophageal reflux disease | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Glossodynia | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Lip dry | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Nausea | 7/12 (58.3%) | 5/12 (41.7%) | 6/12 (50%) | 7/16 (43.8%) | ||||
| Oral disorder | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Oral mucosal blistering | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Salivary gland calculus | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Salivary gland mass | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Stomatitis | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Vomiting | 5/12 (41.7%) | 3/12 (25%) | 2/12 (16.7%) | 5/16 (31.3%) | ||||
| General disorders | ||||||||
| Asthenia | 1/12 (8.3%) | 0/12 (0%) | 3/12 (25%) | 1/16 (6.3%) | ||||
| Axillary pain | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Chest discomfort | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Chest pain | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Chills | 0/12 (0%) | 1/12 (8.3%) | 2/12 (16.7%) | 2/16 (12.5%) | ||||
| Cyst | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 2/16 (12.5%) | ||||
| Early satiety | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Face oedema | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Fatigue | 10/12 (83.3%) | 7/12 (58.3%) | 8/12 (66.7%) | 7/16 (43.8%) | ||||
| Gait disturbance | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Hyperplasia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Induration | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Influenza like illness | 2/12 (16.7%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Irritability | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Malaise | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Medical device pain | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Mucosal inflammation | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Nodule | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Non-cardiac chest pain | 2/12 (16.7%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Oedema | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Oedema peripheral | 4/12 (33.3%) | 2/12 (16.7%) | 2/12 (16.7%) | 3/16 (18.8%) | ||||
| Pain | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Pyrexia | 1/12 (8.3%) | 0/12 (0%) | 3/12 (25%) | 1/16 (6.3%) | ||||
| Spinal pain | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Suprapubic pain | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Swelling | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Temperature intolerance | 2/12 (16.7%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Xerosis | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Infections and infestations | ||||||||
| Abscess | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Cellulitis | 0/12 (0%) | 0/12 (0%) | 3/12 (25%) | 0/16 (0%) | ||||
| Diverticulitis | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Folliculitis | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 2/16 (12.5%) | ||||
| Fungal infection | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Gingivitis | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Hordeolum | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Lower respiratory tract infection | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Nasopharyngitis | 1/12 (8.3%) | 2/12 (16.7%) | 0/12 (0%) | 0/16 (0%) | ||||
| Oral candidiasis | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 2/16 (12.5%) | ||||
| Oral herpes | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Rhinitis | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Sinusitis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Staphylococcal infection | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Tinea pedis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Upper respiratory tract infection | 2/12 (16.7%) | 1/12 (8.3%) | 2/12 (16.7%) | 2/16 (12.5%) | ||||
| Urinary tract infection | 1/12 (8.3%) | 1/12 (8.3%) | 4/12 (33.3%) | 3/16 (18.8%) | ||||
| Vaginal infection | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Vulvitis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Cartilage injury | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Clavicle fracture | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Contusion | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Fall | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Incision site oedema | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Incision site pain | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Radiation necrosis | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Radiation skin injury | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Scar | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Skin wound | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Sunburn | 5/12 (41.7%) | 1/12 (8.3%) | 6/12 (50%) | 3/16 (18.8%) | ||||
| Thermal burn | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Wound secretion | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/12 (8.3%) | 2/12 (16.7%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Amylase increased | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Aspartate aminotransferase increased | 1/12 (8.3%) | 2/12 (16.7%) | 0/12 (0%) | 0/16 (0%) | ||||
| Bilirubin conjugated increased | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Blast cell count increased | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Blood albumin decreased | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Blood alkaline phosphatase increased | 1/12 (8.3%) | 1/12 (8.3%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Blood bicarbonate decreased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Blood bilirubin increased | 2/12 (16.7%) | 0/12 (0%) | 2/12 (16.7%) | 0/16 (0%) | ||||
| Blood creatine phosphokinase increased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Blood creatinine increased | 3/12 (25%) | 0/12 (0%) | 3/12 (25%) | 1/16 (6.3%) | ||||
| Blood lactate dehydrogenase decreased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Blood lactate dehydrogenase increased | 0/12 (0%) | 1/12 (8.3%) | 2/12 (16.7%) | 0/16 (0%) | ||||
| Blood phosphorus increased | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Blood urea increased | 2/12 (16.7%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Breath sounds abnormal | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Carbon dioxide decreased | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Cardiac murmur | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Electrocardiogram QT prolonged | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Eosinophil count increased | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Gamma-glutamyltransferase increased | 1/12 (8.3%) | 2/12 (16.7%) | 1/12 (8.3%) | 3/16 (18.8%) | ||||
| Glomerular filtration rate decreased | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Glomerular filtration rate increased | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Granulocyte count increased | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Hepatic enzyme increased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Lipase increased | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Liver function test abnormal | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Lymph node palpable | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Lymphocyte count decreased | 0/12 (0%) | 2/12 (16.7%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Mean cell haemoglobin concentration increased | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Mean cell volume increased | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Mean platelet volume decreased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Metamyelocyte count increased | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Monocyte count increased | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Myelocyte count increased | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Promyelocyte count increased | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Protein total decreased | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Protein total increased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Protein urine present | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Red cell distribution width increased | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Specific gravity urine decreased | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Specific gravity urine increased | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Urine ketone body present | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Urine leukocyte esterase positive | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Urine output increased | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Weight decreased | 5/12 (41.7%) | 2/12 (16.7%) | 2/12 (16.7%) | 3/16 (18.8%) | ||||
| Weight increased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| White blood cells urine positive | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 3/12 (25%) | 4/12 (33.3%) | 4/12 (33.3%) | 6/16 (37.5%) | ||||
| Dehydration | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Hypercalcaemia | 0/12 (0%) | 2/12 (16.7%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Hyperglycaemia | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Hyperkalaemia | 0/12 (0%) | 2/12 (16.7%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Hypocalcaemia | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Hypokalaemia | 1/12 (8.3%) | 2/12 (16.7%) | 1/12 (8.3%) | 3/16 (18.8%) | ||||
| Hypomagnesaemia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Hyponatraemia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Hypophosphataemia | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Zinc deficiency | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 8/12 (66.7%) | 5/12 (41.7%) | 9/12 (75%) | 9/16 (56.3%) | ||||
| Arthropathy | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Back pain | 0/12 (0%) | 1/12 (8.3%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Bone pain | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Bursitis | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Flank pain | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Joint range of motion decreased | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 2/16 (12.5%) | ||||
| Joint stiffness | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 2/16 (12.5%) | ||||
| Joint swelling | 1/12 (8.3%) | 0/12 (0%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Lower extremity mass | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Muscle atrophy | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Muscle spasms | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Muscular weakness | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Musculoskeletal chest pain | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Musculoskeletal pain | 2/12 (16.7%) | 0/12 (0%) | 3/12 (25%) | 1/16 (6.3%) | ||||
| Musculoskeletal stiffness | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Myalgia | 2/12 (16.7%) | 3/12 (25%) | 3/12 (25%) | 4/16 (25%) | ||||
| Osteoarthritis | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Pain in extremity | 3/12 (25%) | 6/12 (50%) | 3/12 (25%) | 3/16 (18.8%) | ||||
| Pain in jaw | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Periarthritis | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Plantar fasciitis | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Tendonitis | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Upper extremity mass | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Acanthoma | 1/12 (8.3%) | 0/12 (0%) | 2/12 (16.7%) | 0/16 (0%) | ||||
| Acrochordon | 2/12 (16.7%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Basal cell carcinoma | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Fibrous histiocytoma | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Lipoma | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Malignant melanoma | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Melanocytic naevus | 2/12 (16.7%) | 2/12 (16.7%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Seborrhoeic keratosis | 4/12 (33.3%) | 2/12 (16.7%) | 2/12 (16.7%) | 4/16 (25%) | ||||
| Skin papilloma | 1/12 (8.3%) | 3/12 (25%) | 4/12 (33.3%) | 3/16 (18.8%) | ||||
| Tumour haemorrhage | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Tumour pain | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Warty dyskeratoma | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Nervous system disorders | ||||||||
| Amnesia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Aphasia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Ataxia | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Balance disorder | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Convulsion | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Coordination abnormal | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Dizziness | 1/12 (8.3%) | 1/12 (8.3%) | 3/12 (25%) | 2/16 (12.5%) | ||||
| Dysguesia | 1/12 (8.3%) | 3/12 (25%) | 3/12 (25%) | 1/16 (6.3%) | ||||
| Headache | 1/12 (8.3%) | 4/12 (33.3%) | 1/12 (8.3%) | 6/16 (37.5%) | ||||
| Hemiparesis | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Hyperaesthesia | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 2/16 (12.5%) | ||||
| Hypoaesthesia | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Memory impairment | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Neuropathy peripheral | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Nystagmus | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Paraesthesia | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Peripheral sensory neuropathy | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Presyncope | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Sensory disturbance | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Somnolence | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Speech disorder | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Syncope | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| VII nerve paralysis | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 1/12 (8.3%) | 1/12 (8.3%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Confusional state | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Delirium | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Depressed mood | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Depression | 0/12 (0%) | 2/12 (16.7%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Illusion | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Insomnia | 1/12 (8.3%) | 0/12 (0%) | 3/12 (25%) | 0/16 (0%) | ||||
| Libido decreased | 0/12 (0%) | 2/12 (16.7%) | 0/12 (0%) | 0/16 (0%) | ||||
| Mood altered | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Self-induced vomiting | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Dysuria | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Haematuria | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Nocturia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Pollakiuria | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Proteinuria | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Renal failure | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Renal failure acute | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Urinary retention | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Urinary tract disorder | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Urine flow decreased | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Breast mass | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Dysmenorrhoea | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Female genital tract fistula | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Menometrorrhagia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Nipple pain | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Pelvic pain | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Prostatomegaly | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Testicular pain | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Vaginal discharge | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Vaginal haemorrhage | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Vulvovaginal pruritus | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 4/12 (33.3%) | 2/12 (16.7%) | 3/12 (25%) | 4/16 (25%) | ||||
| Dysphonia | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Dyspnoea | 1/12 (8.3%) | 2/12 (16.7%) | 0/12 (0%) | 2/16 (12.5%) | ||||
| Hypoxia | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Nasal congestion | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Nocturnal dyspnoea | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Oropharyngeal pain | 1/12 (8.3%) | 3/12 (25%) | 2/12 (16.7%) | 2/16 (12.5%) | ||||
| Pleurisy | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Productive cough | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Respiratory disorder | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Rhinitis allergic | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Rhinorrhoea | 1/12 (8.3%) | 1/12 (8.3%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Tonsillar disorder | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Wheezing | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Actinic keratosis | 3/12 (25%) | 1/12 (8.3%) | 5/12 (41.7%) | 3/16 (18.8%) | ||||
| Alopecia | 7/12 (58.3%) | 3/12 (25%) | 2/12 (16.7%) | 4/16 (25%) | ||||
| Blister | 1/12 (8.3%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Butterfly rash | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Dermatitis | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Dermatitis acneiform | 4/12 (33.3%) | 1/12 (8.3%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Dermatitis exfoliative | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Drug eruption | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Dry skin | 1/12 (8.3%) | 2/12 (16.7%) | 2/12 (16.7%) | 4/16 (25%) | ||||
| Eczema | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Erythema | 4/12 (33.3%) | 4/12 (33.3%) | 3/12 (25%) | 3/16 (18.8%) | ||||
| Erythema nodosum | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Exfoliative rash | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Hair colour changes | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Hair texture abnormal | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Heat rash | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Hyperhidrosis | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Hyperkeratosis | 4/12 (33.3%) | 2/12 (16.7%) | 6/12 (50%) | 5/16 (31.3%) | ||||
| Ingrown hair | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Keratosis pilaris | 0/12 (0%) | 2/12 (16.7%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Lentigo | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Leukoplakia | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Lichenoid keratosis | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Macule | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Milia | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Nail disorder | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Night sweats | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Pain of skin | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 1/12 (8.3%) | 1/12 (8.3%) | 2/12 (16.7%) | 0/16 (0%) | ||||
| Papule | 2/12 (16.7%) | 2/12 (16.7%) | 0/12 (0%) | 0/16 (0%) | ||||
| Parakeratosis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Perivascular dermatitis | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Photosensitivity reaction | 5/12 (41.7%) | 3/12 (25%) | 5/12 (41.7%) | 0/16 (0%) | ||||
| Pigmentation disorder | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Pruritus | 1/12 (8.3%) | 2/12 (16.7%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Psoriasis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Purpura | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Rash | 3/12 (25%) | 7/12 (58.3%) | 5/12 (41.7%) | 6/16 (37.5%) | ||||
| Rash erythematous | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Rash follicular | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Rash generalised | 2/12 (16.7%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Rash macular | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
| Rash maculo-papular | 1/12 (8.3%) | 0/12 (0%) | 2/12 (16.7%) | 1/16 (6.3%) | ||||
| Rash papular | 1/12 (8.3%) | 1/12 (8.3%) | 2/12 (16.7%) | 2/16 (12.5%) | ||||
| Rash pruritic | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Rash vesicular | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Sebaceous gland disorder | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Skin discolouration | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 0/16 (0%) | ||||
| Skin disorder | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Skin exfoliation | 3/12 (25%) | 1/12 (8.3%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Skin hyperpigmentation | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) | 0/16 (0%) | ||||
| Skin lesion | 1/12 (8.3%) | 3/12 (25%) | 3/12 (25%) | 3/16 (18.8%) | ||||
| Skin mass | 1/12 (8.3%) | 4/12 (33.3%) | 1/12 (8.3%) | 3/16 (18.8%) | ||||
| Skin plaque | 1/12 (8.3%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Skin reaction | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Transient acantholytic dermatosis | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Urticaria | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Vitiligo | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Surgical and medical procedures | ||||||||
| Sinus operation | 0/12 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/16 (0%) | ||||
| Vascular disorders | ||||||||
| Extremity necrosis | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) | 1/16 (6.3%) | ||||
| Flushing | 1/12 (8.3%) | 1/12 (8.3%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Hot flush | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Hypertension | 1/12 (8.3%) | 0/12 (0%) | 1/12 (8.3%) | 2/16 (12.5%) | ||||
| Hypotension | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/16 (0%) | ||||
| Lymphoedema | 0/12 (0%) | 1/12 (8.3%) | 1/12 (8.3%) | 1/16 (6.3%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01107418
Other Study ID Numbers:
- NP25163
First Posted:
Apr 21, 2010
Last Update Posted:
Aug 26, 2015
Last Verified:
Jul 1, 2015