Trial Outcomes & Findings for A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma to the Brain (NCT NCT01266967)

Last Updated: 2014-05-08

Results Overview

OIR is defined as the number of participants whose intracranial response was a confirmed complete response (CR) or partial response (PR) assessed by investigators using modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. CR is defined as disappearance of all lesions. PR is defined as 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). For the primary analysis, OIR was measured when all participants in both treatment arms had two post-Baseline disease assessments. Participants who had an intracranial response of not evaluable or a missing response were treated as non-responders. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

172 participants

Primary outcome timeframe

From the time of the Baseline assessment until disease progression or end of study treatment (average of 18.3 weeks)

Results posted on

2014-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	GSK2118436 150 mg: No Prior Local Therapy Participants who received no prior local therapy for brain metastasis received GSK2118436 150 milligram (mg) capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Study STARTED	89	83
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	89	83

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK2118436 150 mg: No Prior Local Therapy Participants who received no prior local therapy for brain metastasis received GSK2118436 150 milligram (mg) capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Study Death	69	61
Overall Study Study Closed/Terminated	15	17
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	3	3

Baseline Characteristics

A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma to the Brain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK2118436 150 mg: No Prior Local Therapy n=89 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 milligram (mg) capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=83 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	Total n=172 Participants Total of all reporting groups
Age, Continuous	52.3 Years STANDARD_DEVIATION 13.35 • n=39 Participants	52.7 Years STANDARD_DEVIATION 13.83 • n=41 Participants	52.5 Years STANDARD_DEVIATION 13.55 • n=35 Participants
Sex: Female, Male Female	24 Participants n=39 Participants	28 Participants n=41 Participants	52 Participants n=35 Participants
Sex: Female, Male Male	65 Participants n=39 Participants	55 Participants n=41 Participants	120 Participants n=35 Participants
Race/Ethnicity, Customized White	89 participants n=39 Participants	82 participants n=41 Participants	171 participants n=35 Participants
Race/Ethnicity, Customized Not reported	0 participants n=39 Participants	1 participants n=41 Participants	1 participants n=35 Participants

PRIMARY outcome

Timeframe: From the time of the Baseline assessment until disease progression or end of study treatment (average of 18.3 weeks)

Population: V600E Population: all participants with BRAF V600E mutation-positive melanoma who received at least one dose of study treatment

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=74 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=65 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator CR	4 participants	1 participants
Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator PR	26 participants	23 participants

SECONDARY outcome

Timeframe: From the time of the Baseline assessment until disease progression or end of study treatment (average of 24 weeks)

Population: V600E Population

OR is defined as the number of participants achieving either a CR (the disappearance of all target lesions) 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 \[e.g., percent change from Baseline\]) per modified RECIST, version 1.1. To determine the OR, the extracranial response was combined with the intracranial response. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol-scheduled assessment. Participants who had an overall response of not evaluable or a missing response were treated as non-responders.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=74 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=65 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator CR	2 participants	0 participants
Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator PR	28 participants	23 participants

SECONDARY outcome

Timeframe: From the time of the Baseline assessment until disease progression or end of study treatment (average of 17 weeks)

Population: V600K Population: all participants with BRAF V600K mutation-positive melanoma who received at least one dose of study treatment

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=15 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=18 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator CR	0 participants	0 participants
Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator PR	0 participants	5 participants

SECONDARY outcome

Timeframe: From the time of the Baseline assessment until disease progression or end of study treatment (average of 16 weeks)

Population: V600K Population

OIR is defined as the number of participants whose intracranial response was a confirmed complete response (CR) or partial response (PF) assessed by investigators using modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. CR is defined as disappearance of all target lesions. PR is defined as 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). For the primary analysis, OIR was measured when all participants in both treatment arms had two post-Baseline disease assessments. Participants who had an intracranial response of not evaluable or a missing response were treated as non-responders. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=15 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=18 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator CR	0 participants	0 participants
Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator PR	1 participants	4 participants

SECONDARY outcome

Timeframe: Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 27 weeks)

Population: V600E Population. Only the subset of participants who had a complete or partial intracranial response was included in this analysis.

Duration of Intracranial Response is defined as the time from the first documented evidence of intracranial CR (disappearance of all target lesions) 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 \[e.g., percent change from Baseline\]) until the time of the first documented intracranial disease progression (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 millimeters (mm).

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=30 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=24 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants	24.1 weeks Interval 16.1 to 30.3	28.1 weeks Interval 24.1 to 44.1

SECONDARY outcome

Timeframe: Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 31 weeks)

Population: V600K Population. Only the subset of participants who had a complete or partial intracranial response was included in this analysis.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=1 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=4 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Duration of Intracranial Response for the Subset of V600K Mutation-positive Participants	12.4 weeks The confidence interval cannot be calculated because too few participants were V600K mutation positive.	NA weeks Interval 16.6 to The median and the upper limit of the confidence interval cannot be calculated because too few V600K participants had intracranial responses.

SECONDARY outcome

Timeframe: Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 28 weeks)

Population: V600E Population. Only the subset of participants who had a complete or partial response was included in this analysis.

Duration of Overall Response is defined as the time from the first documented evidence of overall CR (disappearance of all target lesions) 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 \[e.g., percent change from Baseline\]) until the time of the first documented disease progression (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 millimeters (mm).

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=30 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=23 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Duration of Overall Response for the Subset of V600E Mutation-positive Participants	27.6 weeks Interval 16.6 to 32.4	23.7 weeks Interval 20.0 to 28.1

SECONDARY outcome

Timeframe: Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 31 weeks)

Population: V600K Population. Only the subset of participants who had a complete or partial response was included in this analysis.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=5 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Duration of Overall Response for the Subset of V600K Mutation-positive Participants	—	36.1 weeks Interval 12.3 to The upper limit of the confidence interval cannot be calculated because too few V600K participants had intracranial responses.

SECONDARY outcome

Timeframe: Time from the first dose of study medication to the earliest of death or progression (average of 23 weeks)

Population: V600E Population

PFS is defined as the time from the first dose of study medication to the earliest of death or progression (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). If a participant received subsequent anti-cancer therapy prior to the date of documented PD/death, the participant was censored at the last adequate assessment and the visit level response was CR (disappearance of all target lesions), 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 \[e.g., percent change from Baseline\]), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=74 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=65 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Progression-free Survival in V600E Mutation-positive Participants	16.1 weeks Interval 15.7 to 23.4	16.0 weeks Interval 15.9 to 23.9

SECONDARY outcome

Timeframe: Time from the first dose of study medication to the earliest of death or progression (average of 17 weeks)

Population: V600K Population

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=15 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=18 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Progression-free Survival in V600K Mutation-positive Participants	8.1 weeks Interval 3.1 to 16.1	15.6 weeks Interval 7.9 to 17.6

SECONDARY outcome

Timeframe: Time from the first dose of study medication until death due to any cause (average of 35 weeks)

Population: V600E Population

Overall survival (OS) is defined as the time from the first dose of study medication until death due to any cause. OS was censored using the date of last known contact for those participants who were alive at the time of analysis.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=74 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=65 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Survival of V600E Mutation-positive Participants	6.8 months Interval 6.1 to 9.2	7.6 months Interval 6.3 to 10.6

SECONDARY outcome

Timeframe: Time from the first dose of study medication until death due to any cause (average of 26 weeks)

Population: V600K Population

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=15 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=18 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Survival in V600K Mutation-positive Participants	3.7 months Interval 1.6 to 5.2	5.0 months Interval 3.1 to 11.9

SECONDARY outcome

Timeframe: From Screening until the conclusion of the study (up to 103 weeks)

Population: All Treated Subjects (ATS) Population: all participants who received at least one dose of study treatment

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=89 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=83 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any AE	81 participants	79 participants
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any SAE	26 participants	31 participants

SECONDARY outcome

Timeframe: From Screening until the conclusion of the study (up to 103 weeks)

Population: ATS Population. Only those participants with data available for the indicated parameters were analyzed.

Clinical chemistry data were summarized at each scheduled assessment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade (G) 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life threatening; Grade 5, death related to toxicity. Blood sample was collected for the assessment of glucose, potassium, magnesium, sodium, phosphorus, potassium. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, total bilirubin, albumin, amylase, cholesterol, creatine kinase, gamma glutamyl transferase (GGT), lipase, blood pH, and triglycerides.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=165 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Glucose (hyperglycemia), AGI, n=165	71 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Glucose (hyperglycemia), Increase to G 3, n=165	8 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Glucose (hyperglycemia), Increase to G 4, n=165	1 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Glucose (hypoglycemia), AGI, n=165	24 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Glucose (hypoglycemia), Increase to G 3, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Glucose (hypoglycemia), Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Magnesium (hypermagnesemia) AGI, n=165	2 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Magnesium (hypermagnesemia), Increase to G 3,n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Magnesium (hypermagnesemia), Increase to G 4,n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Magnesium (hypomagnesemia), AGI, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Magnesium (hypomagnesemia), Increase to G 3, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Magnesium (hypomagnesemia), Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Sodium (hypernatremia), AGI, n=165	8 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Sodium (hypernatremia), Increase to G 3, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Sodium (hypernatremia), Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Sodium (hyponatremia), AGI, n=165	21 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Sodium (hyponatremia), Increase to G 3, n=165	3 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Sodium (hyponatremia), Increase to G. 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Phosphorus inorganic, AGI, n=165	53 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Phosphorus inorganic, Increase to G 3, n=165	13 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Phosphorus inorganic, Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Potassium (hyperkalemia), AGI, n=165	8 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Potassium (hyperkalemia), Increase to G 3, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Potassium (hyperkalemia), Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Potassium (hypokalemia), AGI, n=165	17 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Potassium (hypokalemia), Increase to G 3, n=165	4 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Potassium (hypokalemia), Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters ALP, AGI, n=165	41 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters ALP, Increase to G 3, n=165	1 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters ALP, Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters AST, AGI, n=165	26 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters AST, Increase to G 3, n=165	1 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters AST, Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters ALT, AGI, n=165	27 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters ALT, Increase to G 3, n=165	2 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters ALT, Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Creatinine, AGI, n=165	10 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Creatinine, Increase to G 3, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Creatinine, Increase to G 4, n=165	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Total bilirubin, AGI, n=163	5 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Total bilirubin, Increase to G 3 n=163	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Total bilirubin, Increase to G 4 n=163	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Albumin, AGI, n=27	9 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Albumin, Increase to G 3, n=27	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Albumin, Increase to G 4, n=27	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Amylase, AGI, n=16	3 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Amylase, Increase to G 3, n=16	1 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Amylase, Increase to G 4, n=16	1 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Cholesterol, AGI, n=2	1 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Cholesterol, Increase to G 3, n=2	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Cholesterol, Increase to G 4, n=2	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Creatine kinase, AGI, n=6	1 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Creatine kinase, Increase to G 3, n=6	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Creatine kinase, Increase to G 4, n=6	1 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters GGT, AGI, n=22	13 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters GGT, Increase to G 3, n=22	4 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters GGT, Increase to G 4, n=22	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Lipase, AGI, n=19	10 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Lipase, Increase to G 3, n=19	4 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Lipase, Increase to G 4, n=19	2 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Blood pH, AGI, n=1	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Blood pH, Increase to G 3, n=1	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Blood pH, Increase to G 4, n=1	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Triglycerides, AGI, n=5	3 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Triglycerides, Increase to G 3, n=5	0 participants	—
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters Triglycerides, Increase to G 4, n=5	0 participants	—

SECONDARY outcome

Timeframe: From Screening until the conclusion of the study (up to 103 weeks)

Population: ATS Population

Blood samples were collected for the assessment of hepatobiliary parameters. ALT=alanine aminotranserase; AST=aspartate aminotransferase; ALP=alkaline phosphatase; BIL=total bilirubin; INR=international normalized ratio; ULN=upper limit of normal. Hepato-cellular injury is defined as (ALT/ULN)/(ALP/ULN) \>=5.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=89 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=83 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities Possible HYs Law, >3x ULN ALT, >=2x ULN BIL	0 participants	0 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities Possible HYs Law, >3x ULN ALT, >1.5x ULN INR	0 participants	0 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities Hepato-cellular injury	2 participants	1 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities Bilirubin elevations, >=2x ULN BIL	0 participants	1 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities Bilirubin elevations, >=2x ULN BIL and <2x ULN BIL	0 participants	1 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT or AST elevations, >3x ULN ALT or AST	2 participants	4 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT or AST elevations, >5x ULN ALT or AST	1 participants	1 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT or AST elevations, >8x ULN ALT or AST	1 participants	1 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT or AST elevations, >20x ULN ALT or AST	0 participants	0 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT elevations, >3x ULN ALT	2 participants	4 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT elevations, >5x ULN ALT	1 participants	1 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT elevations, >8x ULN ALT	1 participants	1 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT elevations, >20x ULN ALT	0 participants	0 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALT elevations, >3x ULN ALT, <=3x ULN ALT Baseline	2 participants	4 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALP elevations, >=3x ULN ALP	5 participants	2 participants
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities ALP elevations, >=3x ULN ALP and <3x ULN ALP	4 participants	2 participants

SECONDARY outcome

Timeframe: From Screening until the conclusion of the study (up to 103 weeks)

Population: ATS Population. Only those participants with data available for the indicated parameters were analyzed.

Hematology data were summarized at each scheduled assessment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe, Grade 4, life threatening, Grade 5, death related to toxicity. Blood sample was collected for the assessment of hemoglobin, white blood cells, and platelet count.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=84 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=81 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Hemoglobin (anemia), AGI	25 participants	81 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Hemoglobin (anemia), Increase to Grade 3	2 participants	3 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Hemoglobin (anemia), Increase to Grade 4	0 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Hemoglobin (increased), AGI	1 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Hemoglobin (increased), Increase to Grade 3	0 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Hemoglobin (increased), Increase to Grade 4	0 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Lymphocyte count increased, AGI	0 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Lymphocyte count increased, Increase to Grade 3	0 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Lymphocyte count increased, Increase to Grade 4	0 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Lymphocyte count decreased, AGI	18 participants	81 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Lymphocyte count decreased, Increase Grade 3	4 participants	6 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Lymphocyte count decreased, Increase Grade 4	1 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Total neutrophils, AGI,	6 participants	11 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Total neutrophils, Increase to Grade 3	0 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Total neutrophils, Increase to Grade 4	2 participants	2 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Platelet count, AGI	7 participants	9 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Platelet count, Increase to Grade 3	2 participants	1 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters Platelet count, Increase to Grade 4	1 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters White blood cell count, AGI	9 participants	16 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters White blood cell count, Increase to Grade 3	0 participants	0 participants
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters White blood cell count, Increase to Grade 4	1 participants	1 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36

Population: ATS Population. Only those participants with data available at the indicated time points were analyzed.

Systolic and diastolic blood pressure were measured for all treated participants.

Outcome measures

SECONDARY outcome

Timeframe: Baseline; Weeks 4, 12, 20, 28, 40, 52, and 64

Population: ATS Population. Only those participants with data available at the indicated time points were analyzed.

An increase in the QTc interval corrected using Bazett's formula (Bazett's QTc) was recorded for all treated participants. Grade 1 (450-480 milliseconds \[msec\]), Grade 2 (481-500 msec), Grade 3/4 (\>=501 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=75 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=74 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) Increase from Baseline to any grade	11 participants	17 participants
Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) Increase from Baseline to Grade 2	1 participants	2 participants
Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG) Increase from Baseline to Grade 3/4	0 participants	0 participants

SECONDARY outcome

Timeframe: Weeks (W) 4 and 12

Population: ATS Population

Echocardiograms (ECHO) were measured for all treated participants. An echocardiogram test gives information about the structure and function of the heart. LLN=lower limit of normal (determined by the institution).

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=89 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=83 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 W 4, Left ventricle (LV) ejection fraction < LLN	1 participants	0 participants
Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 W 4, LV ejection fraction < normal	0 participants	0 participants
Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 W 12, LV ejection fraction < LLN	0 participants	0 participants
Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12 W 12, LV ejection fraction < normal	1 participants	0 participants

SECONDARY outcome

Timeframe: Week 4 (pre-dose and 1-3 hours post-dose) and Weeks 8, 16, 24, and 32 (either pre-dose in the morning or in the afternoon at 4-8 hours post-dose)

Population: PK Population: participants in the ATS population for whom a PK sample was obtained and analyzed. Only those participants whose samples were available at the indicated time points were analyzed.

Summary statistics were calculated for each time point by cohort. The population pharmacokinetics were determined using a non-linear mixed effects modeling approach after pooling the data with other studies. These results are reported separately.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=75 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=77 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 4, predose, n=55, 58	31.6 nanograms per milliliter (ng/mL) Interval 7.0 to 2995.0	50.2 nanograms per milliliter (ng/mL) Interval 0.0 to 4293.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 4, 1-3 hours (hrs), n=63, 70	992.1 nanograms per milliliter (ng/mL) Interval 5.0 to 4870.0	810.7 nanograms per milliliter (ng/mL) Interval 4.0 to 4995.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 8, predose, n=36, 36	27.2 nanograms per milliliter (ng/mL) Interval 8.0 to 1148.0	37.5 nanograms per milliliter (ng/mL) Interval 3.0 to 944.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 8, 4-8 hrs, n=19, 25	274.7 nanograms per milliliter (ng/mL) Interval 28.0 to 1062.0	294.5 nanograms per milliliter (ng/mL) Interval 15.0 to 2011.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 16, predose, n=26, 23	27.8 nanograms per milliliter (ng/mL) Interval 6.0 to 3390.0	30.7 nanograms per milliliter (ng/mL) Interval 3.0 to 203.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 16, 4-8 hrs, n=11, 18	341.5 nanograms per milliliter (ng/mL) Interval 33.0 to 1141.0	295.8 nanograms per milliliter (ng/mL) Interval 55.0 to 1808.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 24, predose, n=14, 10	60.7 nanograms per milliliter (ng/mL) Interval 1.0 to 597.0	53.8 nanograms per milliliter (ng/mL) Interval 14.0 to 211.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 24, 4-8 hrs, n=5, 12	371.2 nanograms per milliliter (ng/mL) Interval 0.0 to 1072.0	226.1 nanograms per milliliter (ng/mL) Interval 30.0 to 974.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 32, predose, n=11, 7	38.6 nanograms per milliliter (ng/mL) Interval 7.0 to 777126.0	28.4 nanograms per milliliter (ng/mL) Interval 2.0 to 87.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2118436, Week 32, 4-8 hrs, n=2, 8	227.6 nanograms per milliliter (ng/mL) Interval 90.0 to 365.0	335.7 nanograms per milliliter (ng/mL) Interval 94.0 to 1939.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 4, predose, n=55, 58	62.7 nanograms per milliliter (ng/mL) Interval 9.0 to 1495.0	80.5 nanograms per milliliter (ng/mL) Interval 0.0 to 2931.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 4, 1-3 hrs, n=63, 70	688.9 nanograms per milliliter (ng/mL) Interval 15.0 to 2499.0	593.2 nanograms per milliliter (ng/mL) Interval 8.0 to 2812.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 8, predose, n=36, 36	46.5 nanograms per milliliter (ng/mL) Interval 10.0 to 1743.0	74.4 nanograms per milliliter (ng/mL) Interval 6.0 to 553.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 8, 4-8 hrs, n=19, 25	335.5 nanograms per milliliter (ng/mL) Interval 55.0 to 1114.0	310.5 nanograms per milliliter (ng/mL) Interval 12.0 to 3160.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 16, predose, n=26, 23	45.1 nanograms per milliliter (ng/mL) Interval 10.0 to 824.0	54.4 nanograms per milliliter (ng/mL) Interval 5.0 to 354.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 16, 4-8 hrs, n=11, 18	434.1 nanograms per milliliter (ng/mL) Interval 44.0 to 976.0	456.9 nanograms per milliliter (ng/mL) Interval 148.0 to 1053.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 24, predose, n=14, 10	97.3 nanograms per milliliter (ng/mL) Interval 6.0 to 386.0	103.3 nanograms per milliliter (ng/mL) Interval 14.0 to 325.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 24, 4-8 hrs, n=5, 12	617.1 nanograms per milliliter (ng/mL) Interval 0.0 to 1057.0	357.7 nanograms per milliliter (ng/mL) Interval 79.0 to 959.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 32, predose, n=11, 7	63.1 nanograms per milliliter (ng/mL) Interval 8.0 to 934.0	46.6 nanograms per milliliter (ng/mL) Interval 4.0 to 88.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2285403, Week 32, 4-8 hrs, n=2, 8	375.3 nanograms per milliliter (ng/mL) Interval 118.0 to 633.0	377.5 nanograms per milliliter (ng/mL) Interval 117.0 to 1519.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 4, predose, n=55, 58	3215.8 nanograms per milliliter (ng/mL) Interval 1225.0 to 14064.0	3877.4 nanograms per milliliter (ng/mL) Interval 43.0 to 13435.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 4, 1-3 hrs, n=63, 70	4272.5 nanograms per milliliter (ng/mL) Interval 747.0 to 18161.0	4500.3 nanograms per milliliter (ng/mL) Interval 275.0 to 18196.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 8, predose, n=36, 36	3152.0 nanograms per milliliter (ng/mL) Interval 1564.0 to 10402.0	3250.0 nanograms per milliliter (ng/mL) Interval 667.0 to 12747.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 8, 4-8 hrs, n=19, 25	4692.1 nanograms per milliliter (ng/mL) Interval 2133.0 to 11320.0	5447.5 nanograms per milliliter (ng/mL) Interval 2015.0 to 15009.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 16, predose, n=26, 23	3070.0 nanograms per milliliter (ng/mL) Interval 1143.0 to 11414.0	3561.2 nanograms per milliliter (ng/mL) Interval 922.0 to 10204.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 16, 4-8 hrs, n=11, 18	4865.5 nanograms per milliliter (ng/mL) Interval 2670.0 to 11821.0	6595.7 nanograms per milliliter (ng/mL) Interval 1630.0 to 11380.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 24, predose, n=14, 10	3026.8 nanograms per milliliter (ng/mL) Interval 1532.0 to 14762.0	4199.7 nanograms per milliliter (ng/mL) Interval 2040.0 to 7504.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 24, 4-8 hrs, n=5, 12	3825.9 nanograms per milliliter (ng/mL) Interval 320.0 to 13056.0	5659.9 nanograms per milliliter (ng/mL) Interval 3225.0 to 11009.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 32, predose, n=11, 7	2386.6 nanograms per milliliter (ng/mL) Interval 1421.0 to 6528.0	2451.7 nanograms per milliliter (ng/mL) Interval 1253.0 to 5026.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2298683, Week 32, 4-8 hrs, n=2, 8	11225.8 nanograms per milliliter (ng/mL) Interval 5323.0 to 17129.0	6547.4 nanograms per milliliter (ng/mL) Interval 4578.0 to 8786.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 4, predose, n=55, 58	317.9 nanograms per milliliter (ng/mL) Interval 50.0 to 1338.0	323.0 nanograms per milliliter (ng/mL) Interval 3.0 to 2690.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 4, 1-3 hrs, n=63, 70	351.6 nanograms per milliliter (ng/mL) Interval 62.0 to 1505.0	332.1 nanograms per milliliter (ng/mL) Interval 46.0 to 1619.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 8, predose, n=36, 36	324.1 nanograms per milliliter (ng/mL) Interval 86.0 to 964.0	298.6 nanograms per milliliter (ng/mL) Interval 56.0 to 1272.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 8, 4-8 hrs, n=19, 25	305.4 nanograms per milliliter (ng/mL) Interval 91.0 to 899.0	320.5 nanograms per milliliter (ng/mL) Interval 78.0 to 960.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 16, predose, n=26, 23	285.5 nanograms per milliliter (ng/mL) Interval 93.0 to 1095.0	310.8 nanograms per milliliter (ng/mL) Interval 35.0 to 1200.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 16, 4-8 hrs, n=11, 18	291.1 nanograms per milliliter (ng/mL) Interval 69.0 to 769.0	320.5 nanograms per milliliter (ng/mL) Interval 81.0 to 652.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 24, predose, n=14, 10	304.0 nanograms per milliliter (ng/mL) Interval 94.0 to 875.0	334.0 nanograms per milliliter (ng/mL) Interval 63.0 to 795.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 24, 4-8 hrs, n=5, 12	190.7 nanograms per milliliter (ng/mL) Interval 19.0 to 401.0	287.9 nanograms per milliliter (ng/mL) Interval 106.0 to 599.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 32, predose, n=11, 2	361.2 nanograms per milliliter (ng/mL) Interval 113.0 to 960.0	316.3 nanograms per milliliter (ng/mL) Interval 69.0 to 690.0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542 GSK2167542, Week 32, 4-8 hrs, n=2, 8	227.8 nanograms per milliliter (ng/mL) Interval 225.0 to 231.0	273.9 nanograms per milliliter (ng/mL) Interval 231.0 to 1021.0

SECONDARY outcome

Timeframe: Day 15

This outcome measure could not be analyzed because too few participants participated in the dexamethasone study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening

Population: V600EK and THIDEK Population: all enrolled participants who were V600E or V600K mutation positive by the RGI IUO assay

The BRAF screening assay determines the specific BRAF mutational status (V600 E and K) in participants with metastatic melanoma who may benefit from treatment with GSK2118436. Per RECIST, version 1.1, CR is defined as the disappearance of all lesions. PR is defined as a \>=30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline (BL) sum of the diameters (e.g., percent change from BL). Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as 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 \[smallest sum of diameters recorded since treatment start\]). In addition, the sum must have an absolute increase from nadir of 5 millimeters. Not evaluable: cannot be classified by a preceding definition.

Outcome measures

Outcome measures
Measure	GSK2118436 150 mg: No Prior Local Therapy n=172 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=155 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response Complete response	2 participants	2 participants
Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response Partial response	52 participants	49 participants
Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response Stable disease	78 participants	69 participants
Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response Progressive disease	26 participants	23 participants
Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response Not evaluable	14 participants	12 participants

Adverse Events

GSK2118436 150 mg: No Prior Local Therapy

Serious events: 26 serious events

Other events: 79 other events

Deaths: 0 deaths

GSK2118436 150 mg: Prior Local Therapy

Serious events: 31 serious events

Other events: 74 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	GSK2118436 150 mg: No Prior Local Therapy n=89 Participants Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.	GSK2118436 150 mg: Prior Local Therapy n=83 Participants Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 24, n=22, 25	74.7 millimeters of mercury (mmHg) Standard Deviation 7.87	72.7 millimeters of mercury (mmHg) Standard Deviation 9.99
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 28, n=15, 17	73.9 millimeters of mercury (mmHg) Standard Deviation 6.98	76.5 millimeters of mercury (mmHg) Standard Deviation 8.37
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 32, n=9, 7	73.1 millimeters of mercury (mmHg) Standard Deviation 9.47	73.6 millimeters of mercury (mmHg) Standard Deviation 9.64
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 36, n=2, 1	75.5 millimeters of mercury (mmHg) Standard Deviation 7.78	93.0 millimeters of mercury (mmHg) Standard Deviation NA Standard deviation could not be calculated because only one participant was analyzed in this treatment group at this time point.
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Baseline, n=89, 83	126.6 millimeters of mercury (mmHg) Standard Deviation 16.73	123.9 millimeters of mercury (mmHg) Standard Deviation 14.17
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 4, n=81, 78	122.2 millimeters of mercury (mmHg) Standard Deviation 13.68	121.9 millimeters of mercury (mmHg) Standard Deviation 15.37
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 8, n=70, 73	123.0 millimeters of mercury (mmHg) Standard Deviation 12.71	117.3 millimeters of mercury (mmHg) Standard Deviation 14.53
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 12, 68, 62	123.6 millimeters of mercury (mmHg) Standard Deviation 14.74	120.1 millimeters of mercury (mmHg) Standard Deviation 14.21
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 16, n=52, 52	124.7 millimeters of mercury (mmHg) Standard Deviation 17.70	119.9 millimeters of mercury (mmHg) Standard Deviation 11.67
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 20, n=29, 34	123.7 millimeters of mercury (mmHg) Standard Deviation 16.02	118.9 millimeters of mercury (mmHg) Standard Deviation 13.51
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 24, n=22, 25	126.3 millimeters of mercury (mmHg) Standard Deviation 17.80	120.9 millimeters of mercury (mmHg) Standard Deviation 16.63
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 28, n=15, 17	122.2 millimeters of mercury (mmHg) Standard Deviation 17.03	120.8 millimeters of mercury (mmHg) Standard Deviation 14.32
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 32, n=9, 7	122.8 millimeters of mercury (mmHg) Standard Deviation 14.84	117.7 millimeters of mercury (mmHg) Standard Deviation 10.01
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Systolic BP, Week 36, n=2, 1	119.5 millimeters of mercury (mmHg) Standard Deviation 13.44	128.0 millimeters of mercury (mmHg) Standard Deviation NA Standard deviation could not be calculated because only one participant was analyzed in this treatment group at this time point.
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Baseline, n=89,83	77.7 millimeters of mercury (mmHg) Standard Deviation 8.78	77.1 millimeters of mercury (mmHg) Standard Deviation 9.73
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 4, n=81, 78	74.0 millimeters of mercury (mmHg) Standard Deviation 10.12	74.6 millimeters of mercury (mmHg) Standard Deviation 10.88
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 8, n=70, 73	74.6 millimeters of mercury (mmHg) Standard Deviation 9.14	72.7 millimeters of mercury (mmHg) Standard Deviation 9.54
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 12, n=68, 62	75.2 millimeters of mercury (mmHg) Standard Deviation 7.70	74.3 millimeters of mercury (mmHg) Standard Deviation 11.64
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 16, n=52, 52	73.2 millimeters of mercury (mmHg) Standard Deviation 10.01	71.4 millimeters of mercury (mmHg) Standard Deviation 9.40
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 Diastolic BP, Week 20, n=29, 34	73.6 millimeters of mercury (mmHg) Standard Deviation 9.98	71.7 millimeters of mercury (mmHg) Standard Deviation 9.67