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A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01006980
Collaborator
(none)
675
Enrollment
111
Locations
2
Arms
65.9
Duration (Months)
6.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized, open-label study evaluated the efficacy, safety and tolerability of vemurafenib (RO5185426) as compared to dacarbazine in previously untreated patients with metastatic melanoma. Patients were randomized to receive either vemurafenib 960 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Study treatment was continued until disease progression or unacceptable toxicity occurred. The data and safety monitoring board recommended that patients in the dacarbazine group be allowed to cross over to receive vemurafenib, and the protocol was amended accordingly on January 14, 2011, as both overall survival and progression-free survival endpoints had met the prespecified criteria for statistical significance in favor of vemurafenib.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
675 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
BRIM 3: A Randomized, Open-Label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving Vemurafenib (RO5185426) or Dacarbazine
Study Start Date :
Jan 1, 2010
Actual Primary Completion Date :
Dec 1, 2010
Actual Study Completion Date :
Jul 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Vemurafenib

Drug: Vemurafenib
960 mg (as 240 mg tables) orally twice daily
Other Names:
  • Zelboraf®
  • RO5185426

    		•
    Active Comparator: Dacarbazine

    Drug: Dacarbazine
    1000 mg/m2 intravenously every 3 weeks

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival [From randomization (initiated January 2010) to December 30 2010. Median follow-up time in the vemurafenib group was 3.75 months (range 0.3 to 10.8) and in the dacarbazine group was 2.33 months (range <0.1 to 10.3).]

      An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.

    2. Progression-free Survival [From randomization (initiated January 2010) to December 30 2010.]

      A progression-free survival (PFS) event was defined as disease progression or death due to any cause. Tumor response (progression) was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria using computed tomography (CT) scans or magnetic resonance imaging (MRI).

    Secondary Outcome Measures

    1. Participants With a Best Overall Response (BOR) of Complete Response or Partial Response [From randomization (initiated January 2010) until December 30, 2010]

      BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Participants who never received study treatment and treated participants without any post-baseline tumor assessments were considered as non-responders. CR: Disappearance of all target lesions, all non-target lesions and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion and no new lesion.

    2. Duration of Response [From randomization (initiated in January 2010) until December 30, 2010.]

      Duration of response was defined as the time between the date of the earliest qualifying response and the date of disease progression or death due to any cause. Duration of response was calculated only for participants who had a best overall response of Complete Response or Partial Response and was estimated using the Kaplan-Meier method.

    3. Time to Confirmed Response [From randomization (initiated January 2010) until December 30, 2010.]

      Time to response was defined as the time from randomization to confirmed response (complete response or partial response).

    4. Time to Treatment Failure [approximately 3 years]

      Treatment failure was defined as a secondary endpoint in the protocol, defined as death, disease progression or premature withdrawal of study treatment. This endpoint was not included in the Statistical analysis plan; therefore no analyses of time to treatment failure were performed.

    5. Number of Participants With Adverse Events (AEs) [From randomization (initiated January 2010) until December 30, 2010.]

      The intensity of AEs was graded according to the NCI Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death). A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution, for example is life-threatening, requires hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or requires intervention to prevent one or other of the outcomes listed above.

    6. Pre and Post-dose Plasma Vemurafenib Concentration by Study Day [Plasma samples were collected before the morning dose (troughs) and 2-4 hours after the morning dose at the beginning of each cycle (Days 1, 22, 43, 64, 106, 148 and 190).]

      The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • adults, >/=18 years of age

    • metastatic melanoma, stage IIIC or IV (AJCC)

    • treatment-naïve (no prior systemic anticancer therapy)

    • positive for BRAF V600E mutation

    • measurable disease by RECIST criteria

    • negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion

    Exclusion Criteria:

    • active central nervous system metastases

    • history of carcinomatous meningitis

    • severe cardiovascular disease within 6 months prior to study drug administration

    • previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States 35243
    2 Tucson Arizona United States 85724
    3 Los Angeles California United States 90095-1752
    4 San Francisco California United States 94117
    5 Santa Monica California United States 90404
    6 Aurora Colorado United States 80045
    7 Atlanta Georgia United States 30322
    8 Indianapolis Indiana United States 46202
    9 Boston Massachusetts United States 02114
    10 Boston Massachusetts United States 02115
    11 Boston Massachusetts United States 02215
    12 Detroit Michigan United States 48201
    13 St Louis Missouri United States 63110
    14 New York New York United States 10016
    15 New York New York United States 10065
    16 Chapel Hill North Carolina United States 27514
    17 Portland Oregon United States 97213
    18 Philadelphia Pennsylvania United States 19104
    19 Pittsburgh Pennsylvania United States 15213-2584
    20 Nashville Tennessee United States 37203
    21 Nashville Tennessee United States 37232
    22 Dallas Texas United States 75246
    23 Salt Lake City Utah United States 84112
    24 Seattle Washington United States 98109
    25 Brisbane Australia 4006
    26 Frankston Australia 3199
    27 Malvern Australia 3144
    28 Melbourne Australia 3002
    29 Melbourne Australia 3128
    30 Nedlands Australia 6009
    31 Newcastle Australia 2310
    32 St Leonards Australia 2065
    33 Sydney Australia 2060
    34 Westmead Australia 2145
    35 Woolloongabba Australia 4102
    36 Edmonton Alberta Canada T5J 3N4
    37 Winnipeg Manitoba Canada R2H 2A6
    38 Hamilton Ontario Canada L8V 5C2
    39 Toronto Ontario Canada M4N 3M5
    40 Toronto Ontario Canada M5G 2M9
    41 Montreal Quebec Canada H3A 1A1
    42 Montreal Quebec Canada H3T 1E2
    43 Quebec City Quebec Canada G1R 2J6
    44 Bordeaux France 33075
    45 Lille France 59037
    46 Marseille France 13005
    47 Montpellier France 34298
    48 Nantes France 44093
    49 Nice France 06202
    50 Paris France 75010
    51 Pierre Benite France 69495
    52 Rouen France 76031
    53 Villejuif France 94805
    54 Buxtehude Germany 21614
    55 Dresden Germany 01307
    56 Erfurt Germany 99089
    57 Essen Germany 45122
    58 Frankfurt Germany 60596
    59 Hannover Germany 30449
    60 Heidelberg Germany 69120
    61 Jena Germany 07743
    62 Kiel Germany 24105
    63 Koeln Germany 50924
    64 Leipzig Germany 04103
    65 Mainz Germany 55131
    66 Minden Germany 32429
    67 Muenchen Germany 81377
    68 Regensburg Germany 93053
    69 Tuebingen Germany 72076
    70 Wuerzburg Germany 80337
    71 Jerusalem Israel 91200
    72 Ramat Gan Israel 52621
    73 Tel Aviv Israel 64239
    74 Bari Italy 70124
    75 Genova Italy 16132
    76 Milano Italy 20133
    77 Milano Italy 20141
    78 Milano Italy 20162
    79 Napoli Italy 80131
    80 Roma Italy 00158
    81 Siena Italy 53100
    82 Amsterdam Netherlands 1066 CX
    83 Amsterdam Netherlands 1081 HV
    84 Groningen Netherlands 9713 GZ
    85 Auckland New Zealand
    86 Dunedin New Zealand 9001
    87 Hamilton New Zealand 2001
    88 Palmerston North New Zealand
    89 Wellington New Zealand 6021
    90 Linkoeping Sweden 58185
    91 Lund Sweden 22185
    92 Stockholm Sweden 17176
    93 Umeå Sweden
    94 Uppsala Sweden 75185
    95 Lausanne Switzerland 1011
    96 Zürich Switzerland 8091
    97 Cambridge United Kingdom CB2 2QH
    98 Edinburgh United Kingdom EH4 2XU
    99 Glasgow United Kingdom G12 0YN
    100 London United Kingdom E1 1BB
    101 London United Kingdom NW3 2QG
    102 London United Kingdom SE1 9RT
    103 London United Kingdom SW3 3JJ
    104 Manchester United Kingdom M20 4BX
    105 Newcastle Upon Tyne United Kingdom NE7 7DN
    106 Northwood United Kingdom HA6 2RN
    107 Nottingham United Kingdom NG5 1PB
    108 Oxford United Kingdom OX3 7LJ
    109 Southampton United Kingdom SO16 6YD
    110 Sutton United Kingdom SM2 5PT
    111 Swansea United Kingdom SA2 8QA

    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:
    NCT01006980
    Other Study ID Numbers:
    • NO25026
    • 2009-012293-12
    First Posted:
    Nov 3, 2009
    Last Update Posted:
    Sep 28, 2016
    Last Verified:
    Dec 1, 2015
    Additional relevant MeSH terms:
    Melanoma
    Dacarbazine
    Vemurafenib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 675 participants were randomized, 337 to vemurafenib and 338 to dacarbazine. One participant randomized to dacarbazine was treated in error with vemurafenib throughout the study and is included in the Vemurafenib arm in the table below and for exposure and safety analyses and is included in the dacarbazine arm for efficacy analyses.
    Arm/Group Title Vemurafenib Dacarbazine
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
    Period Title: Vemurafenib and Dacarbazine
    STARTED 337 338
    Treated 336 293
    COMPLETED 0 0
    NOT COMPLETED 337 338
    Period Title: Vemurafenib and Dacarbazine
    STARTED 0 84
    COMPLETED 0 0
    NOT COMPLETED 0 84

    Baseline Characteristics

    Arm/Group Title Vemurafenib Dacarbazine Total
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length). Total of all reporting groups
    Overall Participants 337 338 675
    Age, Customized (participants) [Number]
    < 65 years
    244
    72.4%
    270
    79.9%
    514
    76.1%
    >=65 years
    93
    27.6%
    68
    20.1%
    161
    23.9%
    Sex: Female, Male (Count of Participants)
    Female
    137
    40.7%
    157
    46.4%
    294
    43.6%
    Male
    200
    59.3%
    181
    53.6%
    381
    56.4%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival
    Description An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.
    Time Frame From randomization (initiated January 2010) to December 30 2010. Median follow-up time in the vemurafenib group was 3.75 months (range 0.3 to 10.8) and in the dacarbazine group was 2.33 months (range <0.1 to 10.3).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population was defined as all randomized participants, whether or not study treatment was received. The ITT population was analyzed according to the treatment assigned at randomization. Overall survival was assessed on participants randomized at least 15 days prior to the clinical cutoff date of December 30, 2010.
    Arm/Group Title Vemurafenib Dacarbazine
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
    Measure Participants 336 336
    Participants with events
    43
    12.8%
    75
    22.2%
    Participants without events
    293
    86.9%
    261
    77.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vemurafenib, Dacarbazine
    Comments The trial had a power of 80% to detect a hazard ratio of 0.65 for overall survival with an alpha level of 0.045 (an increase in median survival from 8 months for dacarbazine to 12.3 months for vemurafenib), one interim analysis for overall survival at 50% information.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.37
    Confidence Interval (2-Sided) 95%
    0.26 to 0.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio for death for vemurafenib relative to dacarbazine and the associated 95% confidence interval were computed using an unstratified Cox regression model.
    2. Primary Outcome
    Title Progression-free Survival
    Description A progression-free survival (PFS) event was defined as disease progression or death due to any cause. Tumor response (progression) was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria using computed tomography (CT) scans or magnetic resonance imaging (MRI).
    Time Frame From randomization (initiated January 2010) to December 30 2010.

    Outcome Measure Data

    Analysis Population Description
    The analysis population for PFS consisted of all ITT participants randomized by October 27, 2010 (at least 9 weeks prior to the clinical cutoff date of December 30, 2010). The 9-week interval was chosen to allow time for participants to have had their first scheduled post baseline tumor assessment CT scan.
    Arm/Group Title Vemurafenib Dacarbazine
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
    Measure Participants 275 274
    Participants with events
    104
    30.9%
    182
    53.8%
    Participants without events
    171
    50.7%
    92
    27.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vemurafenib, Dacarbazine
    Comments The trial had a power of 90% to detect a hazard ratio of 0.55 for progression-free survival with an alpha level of 0.005 (an increase in median survival from 2.5 months for dacarbazine to 4.5 months for vemurafenib).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.26
    Confidence Interval (2-Sided) 95%
    0.20 to 0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratios for treatment with vemurafenib, as compared with dacarbazine, were estimated with the use of unstratified Cox regression.
    3. Secondary Outcome
    Title Participants With a Best Overall Response (BOR) of Complete Response or Partial Response
    Description BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Participants who never received study treatment and treated participants without any post-baseline tumor assessments were considered as non-responders. CR: Disappearance of all target lesions, all non-target lesions and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion and no new lesion.
    Time Frame From randomization (initiated January 2010) until December 30, 2010

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all ITT participants randomized by September 22, 2010 (at least 14 weeks prior to the clinical cutoff date of December 30, 2010). The 14-week interval was chosen as it was the minimum time needed to observe a confirmed overall response according to protocol-specified schedule for the first two tumor assessments.
    Arm/Group Title Vemurafenib Dacarbazine
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
    Measure Participants 219 220
    Responders
    106
    31.5%
    12
    3.6%
    Non-responders
    113
    33.5%
    208
    61.5%
    4. Secondary Outcome
    Title Duration of Response
    Description Duration of response was defined as the time between the date of the earliest qualifying response and the date of disease progression or death due to any cause. Duration of response was calculated only for participants who had a best overall response of Complete Response or Partial Response and was estimated using the Kaplan-Meier method.
    Time Frame From randomization (initiated in January 2010) until December 30, 2010.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants randomized by September 22, 2010 and with a best overall confirmed response of complete response or partial response.
    Arm/Group Title Vemurafenib Dacarbazine
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
    Measure Participants 106 12
    Median (95% Confidence Interval) [months]
    5.49
    NA
    5. Secondary Outcome
    Title Time to Confirmed Response
    Description Time to response was defined as the time from randomization to confirmed response (complete response or partial response).
    Time Frame From randomization (initiated January 2010) until December 30, 2010.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants randomized by September 22, 2010 and with a best overall confirmed response of complete response or partial response.
    Arm/Group Title Vemurafenib Dacarbazine
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
    Measure Participants 106 12
    Median (Full Range) [months]
    1.45
    2.72
    6. Secondary Outcome
    Title Time to Treatment Failure
    Description Treatment failure was defined as a secondary endpoint in the protocol, defined as death, disease progression or premature withdrawal of study treatment. This endpoint was not included in the Statistical analysis plan; therefore no analyses of time to treatment failure were performed.
    Time Frame approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vemurafenib Dacarbazine
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
    Measure Participants 0 0
    7. Secondary Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description The intensity of AEs was graded according to the NCI Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death). A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution, for example is life-threatening, requires hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or requires intervention to prevent one or other of the outcomes listed above.
    Time Frame From randomization (initiated January 2010) until December 30, 2010.

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all treated participants who had at least one on-study assessment. The safety population was analyzed according to the treatment received.
    Arm/Group Title Vemurafenib Dacarbazine
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
    Measure Participants 336 282
    Any adverse event
    326
    96.7%
    253
    74.9%
    Serious adverse event
    110
    32.6%
    45
    13.3%
    8. Secondary Outcome
    Title Pre and Post-dose Plasma Vemurafenib Concentration by Study Day
    Description The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.
    Time Frame Plasma samples were collected before the morning dose (troughs) and 2-4 hours after the morning dose at the beginning of each cycle (Days 1, 22, 43, 64, 106, 148 and 190).

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) analysis population included all participants who received vemurafenib and provided valid PK assessments. The PK population at specific time points varied depending on the availability of confirmed dosing and PK assessment times. "n" indicates the number of participants with available PK data at each time point.
    Arm/Group Title Vemurafenib
    Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
    Measure Participants 260
    Pre-Dose Day 1 (n = 260)
    0
    (0)
    Post-Dose Day 1 (n = 255)
    4.3
    (4.35)
    Pre-Dose Day 22 (n = 204)
    53.0
    (26.66)
    Post-Dose Day 22 (n = 221)
    54.0
    (25.67)
    Pre-Dose Day 43 (n = 166)
    54.4
    (24.13)
    Post-Dose Day 43 (n = 170)
    54.4
    (23.28)
    Pre-Dose Day 64 (n = 141)
    57.4
    (23.79)
    Post-Dose Day 64 (n = 138)
    57.7
    (22.29)
    Pre-Dose Day 106 (n = 77)
    55.0
    (17.62)
    Post-Dose Day 106 (n = 75)
    56.3
    (20.36)
    Pre-Dose Day 148 (n = 38)
    51.8
    (24.13)
    Post-Dose Day 148 (n = 39)
    53.3
    (21.55)
    Pre-Dose Day 190 (n = 9)
    53.6
    (12.6)
    Post-Dose Day 190 (n = 9)
    50.5
    (20.16)

    Adverse Events

    Time Frame Baseline through the end of study (maximum exposure: 57.07 months)
    Adverse Event Reporting Description
    Arm/Group Title Vemurafenib Dacarbazine Vemurafenib After Crossover
    Arm/Group Description Adverse events reported for this group include those occurring in participants receiving vemurafenib starting at their baseline visit. Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Adverse events reported for this group include those occurring in participants receiving dacarbazine starting at their baseline visit until study discontinuation or treatment switch. Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length). Adverse events reported for this group include those occurring following switch to vemurafenib in those participants who switched from dacarbazine to vemurafenib during the study.
    All Cause Mortality
    Vemurafenib Dacarbazine Vemurafenib After Crossover
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Vemurafenib Dacarbazine Vemurafenib After Crossover
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 165/336 (49.1%) 52/293 (17.7%) 44/84 (52.4%)
    Blood and lymphatic system disorders
    Anaemia 0/336 (0%) 0/293 (0%) 2/84 (2.4%)
    Bone marrow failure 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Lymphadenitis 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Neutropenia 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Thrombocytopenia 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Atrial fibrillation 3/336 (0.9%) 0/293 (0%) 0/84 (0%)
    Atrial tachycardia 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Cardiac arrest 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Cardiac failure 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Cardiac failure congestive 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Cardiac tamponade 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Cardiopulmonary failure 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Coronary artery disease 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Myocardial infarction 2/336 (0.6%) 0/293 (0%) 0/84 (0%)
    Pericardial effusion 1/336 (0.3%) 0/293 (0%) 1/84 (1.2%)
    Pericarditis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Eye disorders
    Diplopia 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Orbital oedema 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Uveitis 3/336 (0.9%) 0/293 (0%) 0/84 (0%)
    Gastrointestinal disorders
    Abdominal pain 2/336 (0.6%) 1/293 (0.3%) 0/84 (0%)
    Abdominal pain lower 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Abdominal pain upper 1/336 (0.3%) 0/293 (0%) 1/84 (1.2%)
    Constipation 1/336 (0.3%) 0/293 (0%) 1/84 (1.2%)
    Diarrhoea haemorrhagic 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Gastric ulcer 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Gastrointestinal haemorrhage 2/336 (0.6%) 0/293 (0%) 0/84 (0%)
    Gastrointestinal ulcer 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Gastrooesophageal reflux disease 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Intussusception 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Large intestinal obstruction 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Pancreatitis 2/336 (0.6%) 1/293 (0.3%) 0/84 (0%)
    Upper gastrointestinal haemorrhage 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Vomiting 1/336 (0.3%) 0/293 (0%) 1/84 (1.2%)
    General disorders
    Asthenia 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Chest pain 3/336 (0.9%) 0/293 (0%) 0/84 (0%)
    Device occlusion 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Fatigue 2/336 (0.6%) 1/293 (0.3%) 1/84 (1.2%)
    Gait disturbance 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    General physical health deterioration 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Malaise 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Oedema peripheral 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Pyrexia 5/336 (1.5%) 4/293 (1.4%) 3/84 (3.6%)
    Hepatobiliary disorders
    Cholecystitis 1/336 (0.3%) 0/293 (0%) 1/84 (1.2%)
    Hepatitis acute 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Immune system disorders
    Hypersensitivity 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Infections and infestations
    Anal abscess 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Bronchitis 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Cellulitis 1/336 (0.3%) 1/293 (0.3%) 1/84 (1.2%)
    Diverticulitis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Encephalitis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Erysipelas 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Gastroenteritis 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Herpes virus infection 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Intervertebral discitis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Lower respiratory tract infection 1/336 (0.3%) 0/293 (0%) 1/84 (1.2%)
    Lung infection 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Osteomyelitis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Pneumonia 5/336 (1.5%) 2/293 (0.7%) 2/84 (2.4%)
    Sepsis 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Skin infection 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Soft tissue infection 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Upper respiratory tract infection 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Urinary tract infection 1/336 (0.3%) 0/293 (0%) 1/84 (1.2%)
    Viral infection 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Wound infection staphylococcal 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Injury, poisoning and procedural complications
    Fall 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Femoral neck fracture 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Hip fracture 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Multiple injuries 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Investigations
    Alanine aminotransferase increased 1/336 (0.3%) 1/293 (0.3%) 1/84 (1.2%)
    Aspartate aminotransferase increased 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Blood alkaline phosphatase increased 2/336 (0.6%) 0/293 (0%) 0/84 (0%)
    Blood bilirubin increased 2/336 (0.6%) 0/293 (0%) 0/84 (0%)
    Gamma-glutamyltransferase increased 2/336 (0.6%) 0/293 (0%) 2/84 (2.4%)
    International normalised ratio decreased 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Liver function test abnormal 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Neutrophil count decreased 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Metabolism and nutrition disorders
    Dehydration 2/336 (0.6%) 0/293 (0%) 0/84 (0%)
    Diabetes mellitus 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Failure to thrive 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Hypercalcaemia 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Hyperkalaemia 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Hyperuricaemia 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Hypoglycaemia 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Hyponatraemia 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/336 (0.9%) 2/293 (0.7%) 0/84 (0%)
    Bone pain 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Groin pain 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Hypercreatinaemia 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Intervertebral disc protrusion 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Joint effusion 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Musculoskeletal chest pain 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Musculoskeletal pain 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Myalgia 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Neck pain 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Pain in extremity 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Pathological fracture 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Spinal pain 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 10/336 (3%) 2/293 (0.7%) 3/84 (3.6%)
    Bowen's disease 3/336 (0.9%) 0/293 (0%) 0/84 (0%)
    Intracranial tumour haemorrhage 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Keratoacanthoma 36/336 (10.7%) 3/293 (1%) 6/84 (7.1%)
    Malignant melanoma 7/336 (2.1%) 0/293 (0%) 1/84 (1.2%)
    Malignant melanoma in situ 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Skin papilloma 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Squamous cell carcinoma of skin 66/336 (19.6%) 2/293 (0.7%) 12/84 (14.3%)
    Tonsil cancer 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Nervous system disorders
    Aphasia 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Cerebrovascular accident 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Epilepsy 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Headache 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Intraventricular haemorrhage 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Loss of consciousness 2/336 (0.6%) 0/293 (0%) 0/84 (0%)
    Peripheral sensorimotor neuropathy 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Sciatica 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Seizure 2/336 (0.6%) 0/293 (0%) 1/84 (1.2%)
    Sensorimotor disorder 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Syncope 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    VIIth nerve paralysis 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Psychiatric disorders
    Completed suicide 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Confusional state 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Renal and urinary disorders
    Acute kidney injury 3/336 (0.9%) 1/293 (0.3%) 1/84 (1.2%)
    Haemorrhage urinary tract 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Renal failure 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Renal impairment 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Reproductive system and breast disorders
    Cervical dysplasia 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Dyspnoea 3/336 (0.9%) 2/293 (0.7%) 0/84 (0%)
    Epistaxis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Haemoptysis 1/336 (0.3%) 1/293 (0.3%) 0/84 (0%)
    Pleural effusion 3/336 (0.9%) 0/293 (0%) 0/84 (0%)
    Pleuritic pain 2/336 (0.6%) 0/293 (0%) 0/84 (0%)
    Pneumothorax 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Pulmonary embolism 4/336 (1.2%) 2/293 (0.7%) 0/84 (0%)
    Skin and subcutaneous tissue disorders
    Photosensitivity reaction 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Rash 3/336 (0.9%) 0/293 (0%) 0/84 (0%)
    Skin lesion 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Stevens-Johnson syndrome 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Toxic epidermal necrolysis 0/336 (0%) 0/293 (0%) 1/84 (1.2%)
    Vascular disorders
    Deep vein thrombosis 0/336 (0%) 1/293 (0.3%) 1/84 (1.2%)
    Haematoma 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Hypertension 1/336 (0.3%) 0/293 (0%) 1/84 (1.2%)
    Hypertensive crisis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Shock 0/336 (0%) 1/293 (0.3%) 0/84 (0%)
    Subclavian vein thrombosis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Thrombosis 0/336 (0%) 2/293 (0.7%) 0/84 (0%)
    Vasculitis 1/336 (0.3%) 0/293 (0%) 0/84 (0%)
    Other (Not Including Serious) Adverse Events
    Vemurafenib Dacarbazine Vemurafenib After Crossover
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 333/336 (99.1%) 247/293 (84.3%) 83/84 (98.8%)
    Blood and lymphatic system disorders
    Anaemia 32/336 (9.5%) 22/293 (7.5%) 13/84 (15.5%)
    Neutropenia 1/336 (0.3%) 34/293 (11.6%) 0/84 (0%)
    Thrombocytopenia 5/336 (1.5%) 20/293 (6.8%) 1/84 (1.2%)
    Gastrointestinal disorders
    Abdominal Distension 18/336 (5.4%) 5/293 (1.7%) 2/84 (2.4%)
    Abdominal Pain 35/336 (10.4%) 12/293 (4.1%) 3/84 (3.6%)
    Abdominal Pain Upper 37/336 (11%) 8/293 (2.7%) 5/84 (6%)
    Constipation 52/336 (15.5%) 72/293 (24.6%) 8/84 (9.5%)
    Diarrhoea 124/336 (36.9%) 36/293 (12.3%) 24/84 (28.6%)
    Dyspepsia 20/336 (6%) 2/293 (0.7%) 2/84 (2.4%)
    Nausea 132/336 (39.3%) 128/293 (43.7%) 33/84 (39.3%)
    Vomiting 73/336 (21.7%) 77/293 (26.3%) 20/84 (23.8%)
    General disorders
    Asthenia 50/336 (14.9%) 29/293 (9.9%) 7/84 (8.3%)
    Chest Pain 26/336 (7.7%) 5/293 (1.7%) 4/84 (4.8%)
    Chills 23/336 (6.8%) 3/293 (1%) 2/84 (2.4%)
    Fatigue 158/336 (47%) 101/293 (34.5%) 32/84 (38.1%)
    Influenza Like Illness 29/336 (8.6%) 5/293 (1.7%) 3/84 (3.6%)
    Oedema Peripheral 49/336 (14.6%) 15/293 (5.1%) 8/84 (9.5%)
    Pain 30/336 (8.9%) 14/293 (4.8%) 2/84 (2.4%)
    Peripheral Swelling 26/336 (7.7%) 0/293 (0%) 5/84 (6%)
    Pyrexia 71/336 (21.1%) 26/293 (8.9%) 18/84 (21.4%)
    Infections and infestations
    Conjunctivitis 20/336 (6%) 1/293 (0.3%) 2/84 (2.4%)
    Folliculitis 28/336 (8.3%) 3/293 (1%) 2/84 (2.4%)
    Influenza 18/336 (5.4%) 4/293 (1.4%) 3/84 (3.6%)
    Nasopharyngitis 36/336 (10.7%) 10/293 (3.4%) 4/84 (4.8%)
    Upper Respiratory Tract Infection 19/336 (5.7%) 5/293 (1.7%) 4/84 (4.8%)
    Lower respiratory tract infection 8/336 (2.4%) 2/293 (0.7%) 6/84 (7.1%)
    Urinary tract infection 9/336 (2.7%) 9/293 (3.1%) 5/84 (6%)
    Injury, poisoning and procedural complications
    Sunburn 57/336 (17%) 0/293 (0%) 15/84 (17.9%)
    Investigations
    Alanine Aminotransferase Increased 28/336 (8.3%) 4/293 (1.4%) 6/84 (7.1%)
    Aspartate Aminotransferase Increased 25/336 (7.4%) 3/293 (1%) 8/84 (9.5%)
    Blood Alkaline Phosphatase Increased 33/336 (9.8%) 0/293 (0%) 9/84 (10.7%)
    Blood Bilirubin Increased 31/336 (9.2%) 1/293 (0.3%) 2/84 (2.4%)
    Blood Creatinine Increased 28/336 (8.3%) 1/293 (0.3%) 7/84 (8.3%)
    Gamma-Glutamyltransferase Increased 24/336 (7.1%) 4/293 (1.4%) 7/84 (8.3%)
    Weight Decreased 32/336 (9.5%) 8/293 (2.7%) 4/84 (4.8%)
    Metabolism and nutrition disorders
    Decreased Appetite 76/336 (22.6%) 24/293 (8.2%) 20/84 (23.8%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 189/336 (56.3%) 9/293 (3.1%) 48/84 (57.1%)
    Back Pain 53/336 (15.8%) 20/293 (6.8%) 11/84 (13.1%)
    Musculoskeletal Pain 44/336 (13.1%) 11/293 (3.8%) 12/84 (14.3%)
    Myalgia 50/336 (14.9%) 5/293 (1.7%) 15/84 (17.9%)
    Pain In Extremity 76/336 (22.6%) 18/293 (6.1%) 14/84 (16.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Melanocytic Naevus 39/336 (11.6%) 3/293 (1%) 9/84 (10.7%)
    Seborrhoeic Keratosis 46/336 (13.7%) 2/293 (0.7%) 8/84 (9.5%)
    Skin Papilloma 96/336 (28.6%) 1/293 (0.3%) 17/84 (20.2%)
    Nervous system disorders
    Dizziness 41/336 (12.2%) 14/293 (4.8%) 3/84 (3.6%)
    Dysgeusia 55/336 (16.4%) 10/293 (3.4%) 9/84 (10.7%)
    Headache 113/336 (33.6%) 29/293 (9.9%) 23/84 (27.4%)
    Hyperaesthesia 17/336 (5.1%) 1/293 (0.3%) 0/84 (0%)
    Paraesthesia 30/336 (8.9%) 16/293 (5.5%) 6/84 (7.1%)
    Psychiatric disorders
    Depression 21/336 (6.3%) 7/293 (2.4%) 3/84 (3.6%)
    Insomnia 37/336 (11%) 16/293 (5.5%) 7/84 (8.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 52/336 (15.5%) 24/293 (8.2%) 6/84 (7.1%)
    Dyspnoea 33/336 (9.8%) 24/293 (8.2%) 8/84 (9.5%)
    Oropharyngeal Pain 27/336 (8%) 5/293 (1.7%) 3/84 (3.6%)
    Skin and subcutaneous tissue disorders
    Actinic Keratosis 44/336 (13.1%) 12/293 (4.1%) 13/84 (15.5%)
    Alopecia 162/336 (48.2%) 7/293 (2.4%) 25/84 (29.8%)
    Dermal Cyst 26/336 (7.7%) 1/293 (0.3%) 3/84 (3.6%)
    Dermatitis Acneiform 18/336 (5.4%) 1/293 (0.3%) 4/84 (4.8%)
    Dry Skin 80/336 (23.8%) 2/293 (0.7%) 16/84 (19%)
    Erythema 61/336 (18.2%) 4/293 (1.4%) 12/84 (14.3%)
    Hyperkeratosis 99/336 (29.5%) 1/293 (0.3%) 15/84 (17.9%)
    Keratosis Pilaris 32/336 (9.5%) 1/293 (0.3%) 7/84 (8.3%)
    Palmar-Plantar Erythrodysaesthesia Syndrome 34/336 (10.1%) 2/293 (0.7%) 11/84 (13.1%)
    Photosensitivity Reaction 136/336 (40.5%) 13/293 (4.4%) 26/84 (31%)
    Pruritus 86/336 (25.6%) 5/293 (1.7%) 14/84 (16.7%)
    Rash 143/336 (42.6%) 6/293 (2%) 28/84 (33.3%)
    Rash Maculo-Papular 34/336 (10.1%) 1/293 (0.3%) 10/84 (11.9%)
    Skin Exfoliation 18/336 (5.4%) 0/293 (0%) 2/84 (2.4%)
    Skin Lesion 40/336 (11.9%) 4/293 (1.4%) 4/84 (4.8%)
    Acne 15/336 (4.5%) 0/293 (0%) 5/84 (6%)
    Rash erythematous 9/336 (2.7%) 0/293 (0%) 5/84 (6%)
    Vascular disorders
    Flushing 17/336 (5.1%) 6/293 (2%) 2/84 (2.4%)

    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 Hoffman-LaRoche
    Phone 800-821-8590
    Email
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01006980
    Other Study ID Numbers:
    • NO25026
    • 2009-012293-12
    First Posted:
    Nov 3, 2009
    Last Update Posted:
    Sep 28, 2016
    Last Verified:
    Dec 1, 2015