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A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01227889
Recruitment Status : Completed
First Posted : October 25, 2010
Results First Posted : May 16, 2014
Last Update Posted : October 4, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cancer
Interventions Drug: GSK2118436
Drug: Dacarbazine (DTIC)
Enrollment 251
Recruitment Details This was a Phase III randomized, open-label study to compare GSK2118436 to Dacarbazine (DTIC) in previously untreated participants (par.) with BRAF mutation positive advanced (Stage III) or metastatic (Stage IV) melanoma. This study was conducted at 70 centers in 12 countries.
Pre-assignment Details The study has 2 phases: Randomized and Crossover Phase. In Randomized Phase, a total of 250 par. were randomized in 3:1 to receive either oral dabrafenib 150 mg twice daily (BID) or intravenous DTIC 1000 milligram/meter square. Par. in DTIC arm with disease progression were considered for crossover to dabrafenib arm in Crossover Phase
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase
Hide Arm/Group Description Participants (par.) were randomly assigned to receive oral GSK2118436 150 milligrams (mg) twice a day (BID). Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until disease progression (DP), death, the occurrence of an unacceptable adverse event (AE), or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor. In the RP, par. received intravenous (IV) Dacarbazine (DTIC) 1000 mg per meters squared (mg/m^2) every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Par. continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Par. who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Par. who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover par. continued on GSK2118436 until further DP was noted. After DP on GSK2118436, par. were followed for response, progression, survival, and further anti-cancer therapy.
Period Title: Randomized Phase (RP)
Started 187 63
Completed 0 0
Not Completed 187 63
Reason Not Completed
Adverse Event             13             0
Physician Decision             13             5
Progressive Disease             135             52
Study terminated by sponsor             10             0
Missing             1             3
Withdrawal by Subject             15             3
Period Title: Crossover Phase
Started 0 37 [1]
Completed 0 0
Not Completed 0 37
Reason Not Completed
Adverse Event             0             1
Physician Decision             0             3
Progressive Disease             0             31
Study Terminated By Sponsor             0             1
Withdrawal by Subject             0             1
[1]
As of the data cut on December 18, 2012, 36 of 63 participants crossed over from DTIC to GSK2118436.
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase Total
Hide Arm/Group Description Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor. In the RP, par. received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Par. continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Par. who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Par. who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover par. continued on GSK2118436 until further DP was noted. After DP on GSK2118436, par. were followed for response, progression, survival, and further anti-cancer therapy. Total of all reporting groups
Overall Number of Baseline Participants 187 63 250
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 187 participants 63 participants 250 participants
53.5  (13.76) 51.6  (14.22) 53.0  (13.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 187 participants 63 participants 250 participants
Female
75
  40.1%
26
  41.3%
101
  40.4%
Male
112
  59.9%
37
  58.7%
149
  59.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 187 participants 63 participants 250 participants
White 186 63 249
Missing 1 0 1
1.Primary Outcome
Title Progression-free Survival (PFS) as Assessed by the Investigator
Hide Description PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). For participants who did not progress or die, PFS was censored at the date of last contact. Data are presented as median and 96% confidence interval.
Time Frame Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants regardless of whether or not treatment was administered
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP
Hide Arm/Group Description:
Participants were randomly assigned to receive oral GSK2118436 150 milligrams (mg) twice a day (BID). Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until disease progression (DP), death, the occurrence of an unacceptable adverse event (AE), or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
In the RP, participants received intravenous (IV) Dacarbazine (DTIC) 1000 milligrams per meters squared (mg/m^2) every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study.
Overall Number of Participants Analyzed 187 63
Median (95% Confidence Interval)
Unit of Measure: Months
6.9
(5.5 to 9.0)
2.7
(1.4 to 3.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK2118436 150 mg BID, DTIC 1000 mg/m^2 in RP
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p value from a stratified log-rank test was adjusted for disease stage at screening.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.26 to 0.60
Estimation Comments HRs were estimated using a Pike estimator. HR from a stratified log-rank test was adjusted for disease stage at screening.
2.Primary Outcome
Title Progression-free Survival (PFS) as Assessed by an Independent Radiologist: Randomized Phase
Hide Description PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by an independent radiologist according to RECIST version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact.
Time Frame Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP
Hide Arm/Group Description:
Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study.
Overall Number of Participants Analyzed 187 63
Median (95% Confidence Interval)
Unit of Measure: Months
6.7
(5.0 to 6.9)
2.9
(1.7 to 4.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK2118436 150 mg BID, DTIC 1000 mg/m^2 in RP
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.20 to 0.61
Estimation Comments HRs were estimated using a Pike estimator. HR was adjusted for disease stage at screening.
3.Secondary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, overall survival was censored at the date of last contact.
Time Frame Time interval between the date of randomization and the date of death due to any cause (up to 22.1 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP
Hide Arm/Group Description:
Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants. continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study.
Overall Number of Participants Analyzed 187 63
Median (95% Confidence Interval)
Unit of Measure: Months
20.0
(16.7 to 24.2)
15.6
(11.9 to 21.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK2118436 150 mg BID, DTIC 1000 mg/m^2 in RP
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.57 to 1.18
Estimation Comments HRs were estimated using a Pike estimator. HR was adjusted for disease stage at screening.
4.Secondary Outcome
Title Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Randomized Phase
Hide Description A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). Response was evaluated by an investigator per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR.
Time Frame From randomization until the first documented evidence of a confirmed complete response or partial response (median of 6.6 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP
Hide Arm/Group Description:
Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until disease DP, death, the occurrence of an unacceptable adverse AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study.
Overall Number of Participants Analyzed 187 63
Measure Type: Number
Unit of Measure: participants
CR 26 4
PR 86 11
5.Secondary Outcome
Title Number of Participants With a Best Overall Response of Confirmed CR or PR as Assessed by an Independent Radiologist: Randomized Phase
Hide Description A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). Response was evaluated by an independent radiologist per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR.
Time Frame From randomization until the first documented evidence of a confirmed complete response or partial response (median of 12.0 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP
Hide Arm/Group Description:
Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until disease DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study.
Overall Number of Participants Analyzed 187 63
Measure Type: Number
Unit of Measure: participants
CR 6 1
PR 87 3
6.Secondary Outcome
Title Duration of Response as Assessed by the Investigator: Randomized Phase
Hide Description Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of PD or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm.
Time Frame Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 65.6 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with a confirmed CR or PR were assessed for duration of response.
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP
Hide Arm/Group Description:
Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study.
Overall Number of Participants Analyzed 112 15
Median (95% Confidence Interval)
Unit of Measure: Months
9.2
(7.4 to 11.9)
8.2
(3.5 to 18.3)
7.Secondary Outcome
Title Duration of Response as Assessed by an Independent Radiologist: Randomized Phase
Hide Description Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of PD or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. NA indicates that data is not available.
Time Frame Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 7.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with a confirmed CR or PR were assessed for duration of response.
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP
Hide Arm/Group Description:
Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study.
Overall Number of Participants Analyzed 93 4
Median (95% Confidence Interval)
Unit of Measure: Months
5.5
(5.0 to 6.7)
NA [1] 
(NA to NA)
[1]
Median duration of response could not be calculated because there were not enough participants with a CR or PR.
8.Secondary Outcome
Title Progression-free Survival (PFS2) as Assessed by the Investigator: Crossover Phase
Hide Description PFS2 is defined as the time from the first dose of GSK2118436, in participants randomized to DTIC who crossed over to GSK2118436 after initial progression, to the earliest date of radiographic or photographic disease progression or death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact.
Time Frame Time from first dose of GSK2118436 in participants who crossover after initial progression to the earliest date of radiographical or photographical PD or death due to any cause (up to 6.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Crossover Treatment Population: the subset of participants who were randomized to the DTIC arm, and who elected at the point of disease progression to receive GSK2118436. Only participants who received at least one dose of GSK2118436 were included in the Crossover Treatment Population.
Arm/Group Title GSK25118436 in Crossover Phase
Hide Arm/Group Description:
Participants who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Participants who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover participants continued on GSK2118436 until further DP was noted. After DP on GSK2118436, participants were followed for response, progression, survival, and further anti-cancer therapy.
Overall Number of Participants Analyzed 37
Median (95% Confidence Interval)
Unit of Measure: Months
4.3
(4.1 to 6.1)
9.Secondary Outcome
Title Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Crossover Phase
Hide Description A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). Response was evaluated by an investigator per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR.
Time Frame From randomization until the first documented evidence of a confirmed complete response or partial response (up to 6.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Crossover Treatment Population. At the time data were analyzed for overall response, only 37 participants had crossed over from DTIC treatment to GSK25118436 treatment.
Arm/Group Title GSK25118436 in Crossover Phase
Hide Arm/Group Description:
Participants who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Participants who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover participants continued on GSK2118436 until further DP was noted. After DP on GSK2118436, participants were followed for response, progression, survival, and further anti-cancer therapy.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: participants
CR 0
PR 12
10.Secondary Outcome
Title Duration of Response as Assessed by the Investigator: Crossover Phase
Hide Description Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of PD or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm.
Time Frame Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 6.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Crossover Population. Only participants with a confirmed CR or PR were assessed for duration of response.
Arm/Group Title GSK25118436 in Crossover Phase
Hide Arm/Group Description:
Participants who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Participants who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover participants continued on GSK2118436 until further DP was noted. After DP on GSK2118436, participants were followed for response, progression, survival, and further anti-cancer therapy.
Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: Months
4.4
(2.5 to 6.2)
11.Secondary Outcome
Title Number of Participants With Non-melanoma Skin Lesions: Randomized Phase
Hide Description Dermatological examinations were performed by the investigator, or at the discretion of the investigator, referred to a dermatologist. The number of participants with non-melanoma skin lessions was assessed from the time of Screening until study completion or discontinuation from the study for any reason.
Time Frame From Screening until study completion or discontinuation from the study (up to 9.9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all randomized participants who received at least one dose of study drug, based on the actual treatment received, if this differed from that to which the participant was randomized
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP
Hide Arm/Group Description:
Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor.
In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study.
Overall Number of Participants Analyzed 187 59
Measure Type: Number
Unit of Measure: participants
Number of Subjects with Event 14 0
Number of Events 24 0
12.Secondary Outcome
Title Agreement Rate for V600E Mutation Validation of the BRAF Mutation Assay
Hide Description Analytical and clinical validation of the companion diagnostic (cDx) assay was performed to determine the extent of agreement between the bioMerieux cDx assay (THxID BRAF Assay) and the Clinical Trial Assay (CTA) to detect BRAF mutations to determine participant eligibility into the study. Skin tissue samples collected at the Screening visit were used for this analysis. Multiple specimen per participant were analyzed.
Time Frame Screening
Hide Outcome Measure Data
Hide Analysis Population Description
V600E positive participants screened for BREAK-3 study
Arm/Group Title All Screened Participants
Hide Arm/Group Description:
Specimens were tested for V600E mutations to determine trial eligibility with the CTA were retested with the THxID BRAF test. The analytical agreement between the THxID BRAF and the CTA was evaluated for both mutation positive and mutation negative specimens from all sites.
Overall Number of Participants Analyzed 734
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent agreement
Agreement for V600E
96.70
(93.6 to 98.3)
Agreement for V600K
90.00
(78.6 to 95.7)
Agreement for mutation negative
95.00
(91.6 to 97.0)
Agreement for overall
94.90
(92.7 to 96.4)
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to the end of the study. The total duration of the study including a long-term follow-up phase was up to 5 years.
Adverse Event Reporting Description SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study drug, based on the actual treatment received, if this differed from that to which the participant was randomized.
 
Arm/Group Title GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP GSK25118436 in the Crossover Phase
Hide Arm/Group Description Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor. In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Participants who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover participants continued on GSK2118436 until further DP was noted. After DP on GSK2118436, participants were followed for response, progression, survival, and further anti-cancer therapy.
All-Cause Mortality
GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP GSK25118436 in the Crossover Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/187 (2.67%)      0/59 (0.00%)      1/37 (2.70%)    
Show Serious Adverse Events Hide Serious Adverse Events
GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP GSK25118436 in the Crossover Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   64/187 (34.22%)      14/59 (23.73%)      9/37 (24.32%)    
Blood and lymphatic system disorders       
Anaemia  1  1/187 (0.53%)  1 1/59 (1.69%)  1 0/37 (0.00%)  0
Febrile neutropenia  1  1/187 (0.53%)  1 1/59 (1.69%)  1 0/37 (0.00%)  0
Lymphadenopathy  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Neutropenia  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Cardiac disorders       
Acute coronary syndrome  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Acute myocardial infarction  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Angina pectoris  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Atrial fibrillation  1  3/187 (1.60%)  3 0/59 (0.00%)  0 0/37 (0.00%)  0
Cardiac failure congestive  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Myocardial infarction  1  2/187 (1.07%)  2 0/59 (0.00%)  0 0/37 (0.00%)  0
Myocardial ischaemia  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Eye disorders       
Cataract  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Eyelid oedema  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Macular hole  1  0/187 (0.00%)  0 0/59 (0.00%)  0 1/37 (2.70%)  1
Gastrointestinal disorders       
Abdominal pain  1  1/187 (0.53%)  1 2/59 (3.39%)  2 1/37 (2.70%)  1
Colitis  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Constipation  1  1/187 (0.53%)  1 1/59 (1.69%)  1 0/37 (0.00%)  0
Diarrhoea  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Haemorrhoidal haemorrhage  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Ileus  1  1/187 (0.53%)  2 0/59 (0.00%)  0 0/37 (0.00%)  0
Large intestine perforation  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Nausea  1  1/187 (0.53%)  2 1/59 (1.69%)  1 0/37 (0.00%)  0
Pancreatic necrosis  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Pancreatitis  1  2/187 (1.07%)  2 0/59 (0.00%)  0 0/37 (0.00%)  0
Pancreatitis acute  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Small intestinal perforation  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Vomiting  1  2/187 (1.07%)  3 1/59 (1.69%)  1 0/37 (0.00%)  0
Ascites  1  0/187 (0.00%)  0 0/59 (0.00%)  0 1/37 (2.70%)  1
General disorders       
Chills  1  4/187 (2.14%)  4 0/59 (0.00%)  0 0/37 (0.00%)  0
Euthanasia  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Gait disturbance  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Influenza like illness  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Pain  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Pyrexia  1  10/187 (5.35%)  13 0/59 (0.00%)  0 1/37 (2.70%)  1
Hepatobiliary disorders       
Cholecystitis  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Hepatic pain  1  1/187 (0.53%)  1 1/59 (1.69%)  1 0/37 (0.00%)  0
Infections and infestations       
Abdominal infection  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Anal abscess  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Cellulitis  1  1/187 (0.53%)  2 0/59 (0.00%)  0 0/37 (0.00%)  0
Erysipelas  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Gastrointestinal infection  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Hepatitis E  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Localised infection  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Perineal abscess  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Pleural infection  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Pneumonia  1  2/187 (1.07%)  2 0/59 (0.00%)  0 1/37 (2.70%)  1
Sepsis  1  0/187 (0.00%)  0 1/59 (1.69%)  1 1/37 (2.70%)  1
Streptococcal infection  1  0/187 (0.00%)  0 0/59 (0.00%)  0 1/37 (2.70%)  1
Injury, poisoning and procedural complications       
Head injury  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Radius fracture  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Investigations       
Blood bilirubin increased  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Blood creatine phosphokinase increased  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Blood creatinine increased  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Ejection fraction decreased  1  3/187 (1.60%)  5 0/59 (0.00%)  0 0/37 (0.00%)  0
White blood cell count decreased  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Metabolism and nutrition disorders       
Dehydration  1  2/187 (1.07%)  2 0/59 (0.00%)  0 0/37 (0.00%)  0
Diabetes mellitus  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Diabetes mellitus inadequate control  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Hyperlipasaemia  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Hyponatraemia  1  1/187 (0.53%)  1 0/59 (0.00%)  0 1/37 (2.70%)  1
Hypophosphataemia  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/187 (0.53%)  1 0/59 (0.00%)  0 1/37 (2.70%)  1
Back pain  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Joint effusion  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Muscular weakness  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Musculoskeletal pain  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Osteoporotic fracture  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Pain in extremity  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acoustic neuroma  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Adenocarcinoma of the cervix  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Basal cell carcinoma  1  6/187 (3.21%)  8 0/59 (0.00%)  0 0/37 (0.00%)  0
Bowen’s disease  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Breast cancer  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Focal nodular hyperplasia  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Lip squamous cell carcinoma  1  1/187 (0.53%)  1 0/59 (0.00%)  0 2/37 (5.41%)  2
Malignant melanoma  1  3/187 (1.60%)  3 0/59 (0.00%)  0 0/37 (0.00%)  0
Malignant melanoma in situ  1  3/187 (1.60%)  3 0/59 (0.00%)  0 0/37 (0.00%)  0
Malignant melanoma stage I  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Papillary thyroid cancer  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Soft tissue sarcoma  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Squamous cell carcinoma  1  7/187 (3.74%)  11 0/59 (0.00%)  0 2/37 (5.41%)  2
Squamous cell carcinoma of skin  1  8/187 (4.28%)  12 0/59 (0.00%)  0 2/37 (5.41%)  3
Fibrous histiocytoma  1  0/187 (0.00%)  0 0/59 (0.00%)  0 1/37 (2.70%)  1
Nervous system disorders       
Lethargy  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Parkinsonism  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Presyncope  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Syncope  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Transient ischaemic attack  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Psychiatric disorders       
Depression  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Psychotic disorder  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Renal and urinary disorders       
Haematuria  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Renal failure  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Urinary bladder polyp  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Reproductive system and breast disorders       
Ovarian cyst  1  0/187 (0.00%)  0 0/59 (0.00%)  0 1/37 (2.70%)  1
Respiratory, thoracic and mediastinal disorders       
Hypoxia  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Pleural effusion  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Pleuritic pain  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Pulmonary embolism  1  2/187 (1.07%)  2 1/59 (1.69%)  1 0/37 (0.00%)  0
Pulmonary oedema  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Respiratory distress  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Respiratory failure  1  0/187 (0.00%)  0 0/59 (0.00%)  0 1/37 (2.70%)  1
Skin and subcutaneous tissue disorders       
Dermal cyst  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Hyperhidrosis  1  0/187 (0.00%)  0 1/59 (1.69%)  1 0/37 (0.00%)  0
Vascular disorders       
Haematoma  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Haemorrhage  1  1/187 (0.53%)  1 0/59 (0.00%)  0 0/37 (0.00%)  0
Hypotension  1  2/187 (1.07%)  4 0/59 (0.00%)  0 1/37 (2.70%)  1
1
Term from vocabulary, 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GSK2118436 150 mg BID DTIC 1000 mg/m^2 in RP GSK25118436 in the Crossover Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   181/187 (96.79%)      51/59 (86.44%)      37/37 (100.00%)    
Blood and lymphatic system disorders       
Anaemia  1  10/187 (5.35%)  14 7/59 (11.86%)  9 3/37 (8.11%)  5
Leukopenia  1  0/187 (0.00%)  0 8/59 (13.56%)  8 0/37 (0.00%)  0
Neutropenia  1  0/187 (0.00%)  0 10/59 (16.95%)  18 0/37 (0.00%)  0
Thrombocytopenia  1  0/187 (0.00%)  0 8/59 (13.56%)  11 0/37 (0.00%)  0
Lymphopenia  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Gastrointestinal disorders       
Abdominal pain  1  15/187 (8.02%)  16 7/59 (11.86%)  8 8/37 (21.62%)  10
Abdominal pain upper  1  11/187 (5.88%)  20 0/59 (0.00%)  0 3/37 (8.11%)  4
Constipation  1  27/187 (14.44%)  32 8/59 (13.56%)  9 4/37 (10.81%)  4
Diarrhoea  1  31/187 (16.58%)  42 7/59 (11.86%)  8 4/37 (10.81%)  5
Nausea  1  55/187 (29.41%)  69 29/59 (49.15%)  49 9/37 (24.32%)  9
Vomiting  1  42/187 (22.46%)  55 15/59 (25.42%)  19 5/37 (13.51%)  5
Abdominal distension  1  0/187 (0.00%)  0 0/59 (0.00%)  0 3/37 (8.11%)  3
General disorders       
Asthenia  1  37/187 (19.79%)  56 9/59 (15.25%)  11 6/37 (16.22%)  8
Chills  1  23/187 (12.30%)  40 0/59 (0.00%)  0 4/37 (10.81%)  5
Fatigue  1  48/187 (25.67%)  57 14/59 (23.73%)  21 6/37 (16.22%)  6
Influenza like illness  1  14/187 (7.49%)  16 0/59 (0.00%)  0 2/37 (5.41%)  2
Oedema peripheral  1  12/187 (6.42%)  13 5/59 (8.47%)  5 0/37 (0.00%)  0
Pyrexia  1  61/187 (32.62%)  102 8/59 (13.56%)  8 9/37 (24.32%)  11
Non-cardiac chest pain  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Oedema peripheral  1  0/187 (0.00%)  0 0/59 (0.00%)  0 3/37 (8.11%)  3
Peripheral swelling  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  5
Infections and infestations       
Folliculitis  1  11/187 (5.88%)  13 0/59 (0.00%)  0 0/37 (0.00%)  0
Nasopharyngitis  1  35/187 (18.72%)  57 4/59 (6.78%)  6 4/37 (10.81%)  8
Upper respiratory tract infection  1  12/187 (6.42%)  15 0/59 (0.00%)  0 2/37 (5.41%)  2
Urinary tract infection  1  0/187 (0.00%)  0 4/59 (6.78%)  4 0/37 (0.00%)  0
Sinusitis  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
INFLUENZA  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Investigations       
Alanine aminotransferase increased  1  12/187 (6.42%)  13 0/59 (0.00%)  0 0/37 (0.00%)  0
Aspartate aminotransferase increased  1  10/187 (5.35%)  10 0/59 (0.00%)  0 0/37 (0.00%)  0
Lymphocyte count decreased  1  0/187 (0.00%)  0 3/59 (5.08%)  7 2/37 (5.41%)  3
Platelet count decreased  1  0/187 (0.00%)  0 4/59 (6.78%)  5 0/37 (0.00%)  0
Weight decreased  1  13/187 (6.95%)  13 0/59 (0.00%)  0 2/37 (5.41%)  2
White blood cell count decreased  1  0/187 (0.00%)  0 3/59 (5.08%)  7 0/37 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  26/187 (13.90%)  34 6/59 (10.17%)  7 4/37 (10.81%)  5
Hyperglycaemia  1  14/187 (7.49%)  19 3/59 (5.08%)  4 3/37 (8.11%)  4
Hypophosphataemia  1  11/187 (5.88%)  13 0/59 (0.00%)  0 2/37 (5.41%)  2
Hypoglycaemia  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Hypokalaemia  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Musculoskeletal and connective tissue disorders       
Arthralgia  1  74/187 (39.57%)  111 0/59 (0.00%)  0 16/37 (43.24%)  23
Back pain  1  41/187 (21.93%)  48 4/59 (6.78%)  4 8/37 (21.62%)  8
Musculoskeletal chest pain  1  10/187 (5.35%)  10 0/59 (0.00%)  0 3/37 (8.11%)  3
Musculoskeletal pain  1  18/187 (9.63%)  20 0/59 (0.00%)  0 6/37 (16.22%)  9
Myalgia  1  32/187 (17.11%)  41 0/59 (0.00%)  0 7/37 (18.92%)  7
Pain in extremity  1  31/187 (16.58%)  40 6/59 (10.17%)  7 6/37 (16.22%)  6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acrochordon  1  11/187 (5.88%)  20 0/59 (0.00%)  0 0/37 (0.00%)  0
Melanocytic naevus  1  11/187 (5.88%)  18 0/59 (0.00%)  0 0/37 (0.00%)  0
Papilloma  1  15/187 (8.02%)  23 0/59 (0.00%)  0 2/37 (5.41%)  2
Seborrhoeic keratosis  1  23/187 (12.30%)  55 0/59 (0.00%)  0 3/37 (8.11%)  3
Skin papilloma  1  48/187 (25.67%)  85 0/59 (0.00%)  0 10/37 (27.03%)  15
Dysplastic naevus  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  4
Fibroma  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Fibrous histiocytoma  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Keratoacanthoma  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  5
Nervous system disorders       
Dizziness  1  15/187 (8.02%)  17 3/59 (5.08%)  3 5/37 (13.51%)  5
Headache  1  68/187 (36.36%)  109 5/59 (8.47%)  6 6/37 (16.22%)  7
Paraesthesia  1  12/187 (6.42%)  13 0/59 (0.00%)  0 3/37 (8.11%)  3
Hyperaesthesia  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  3
Sciatica  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Psychiatric disorders       
Anxiety  1  10/187 (5.35%)  10 5/59 (8.47%)  5 3/37 (8.11%)  3
Insomnia  1  16/187 (8.56%)  19 0/59 (0.00%)  0 0/37 (0.00%)  0
Depression  1  0/187 (0.00%)  0 0/59 (0.00%)  0 3/37 (8.11%)  3
Renal and urinary disorders       
Pollakiuria  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Reproductive system and breast disorders       
Pelvic pain  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Respiratory, thoracic and mediastinal disorders       
Cough  1  34/187 (18.18%)  42 4/59 (6.78%)  6 2/37 (5.41%)  2
Dyspnoea  1  22/187 (11.76%)  28 0/59 (0.00%)  0 2/37 (5.41%)  2
Dyspnoea exertional  1  0/187 (0.00%)  0 3/59 (5.08%)  3 0/37 (0.00%)  0
Oropharyngeal pain  1  10/187 (5.35%)  12 0/59 (0.00%)  0 3/37 (8.11%)  3
Nasal congestion  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Skin and subcutaneous tissue disorders       
Actinic keratosis  1  22/187 (11.76%)  51 0/59 (0.00%)  0 2/37 (5.41%)  2
Alopecia  1  54/187 (28.88%)  59 0/59 (0.00%)  0 7/37 (18.92%)  7
Dry skin  1  28/187 (14.97%)  36 0/59 (0.00%)  0 5/37 (13.51%)  5
Eczema  1  10/187 (5.35%)  10 0/59 (0.00%)  0 0/37 (0.00%)  0
Erythema  1  18/187 (9.63%)  28 0/59 (0.00%)  0 0/37 (0.00%)  0
Hair texture abnormal  1  13/187 (6.95%)  14 0/59 (0.00%)  0 0/37 (0.00%)  0
Hyperkeratosis  1  71/187 (37.97%)  156 0/59 (0.00%)  0 11/37 (29.73%)  20
Palmar-plantar erythrodysaesthesia syndrome  1  37/187 (19.79%)  44 0/59 (0.00%)  0 5/37 (13.51%)  5
Palmoplantar keratoderma  1  17/187 (9.09%)  20 0/59 (0.00%)  0 2/37 (5.41%)  2
Photosensitivity reaction  1  0/187 (0.00%)  0 4/59 (6.78%)  4 2/37 (5.41%)  2
Pruritus  1  11/187 (5.88%)  13 0/59 (0.00%)  0 3/37 (8.11%)  3
Rash  1  35/187 (18.72%)  45 0/59 (0.00%)  0 10/37 (27.03%)  13
Skin lesion  1  14/187 (7.49%)  18 0/59 (0.00%)  0 2/37 (5.41%)  3
Hyperhidrosis  1  0/187 (0.00%)  0 0/59 (0.00%)  0 3/37 (8.11%)  3
Night sweats  1  0/187 (0.00%)  0 0/59 (0.00%)  0 4/37 (10.81%)  4
Skin exfoliation  1  0/187 (0.00%)  0 0/59 (0.00%)  0 2/37 (5.41%)  2
Vascular disorders       
Hypertension  1  10/187 (5.35%)  16 0/59 (0.00%)  0 0/37 (0.00%)  0
1
Term from vocabulary, 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01227889     History of Changes
Other Study ID Numbers: 113683
First Submitted: October 21, 2010
First Posted: October 25, 2010
Results First Submitted: June 6, 2013
Results First Posted: May 16, 2014
Last Update Posted: October 4, 2017