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A Study to Evaluate the Effect of Repeat Oral Dosing of GSK2118436 on Cardiac Repolarization in Subjects With V600 BRAF Mutation-Positive Tumors

NCT01738451 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 50

Last updated 2017-11-13

No results posted yet for this study

Summary

This is a Phase I, multicenter, 2-part study with Part 1 designed as a safety lead-in and Part 2 designed to evaluate the effect of GSK2118436 on cardiac repolarization (corrected QT interval \[QTc\] duration) as compared with placebo in subjects with V600 BRAF mutation-positive tumors.

Each part of the study will consist of screening (14 days prior to the start of the study treatment), treatment and follow-up period (14 days).

In Part 1 in Cohort 1 six subjects will receive GSK2118436 225 mg twice a day (BID) on study days 1 to 7 and a single 225 milligram (mg) dose on morning of Day 8. Based on the safety data of subjects in Cohort 1 subjects will be enrolled in Cohort 2 and the dose of GSK2118436 will be escalated to 300 mg BID. If the 225 mg dose of GSK2118436 is not well tolerated in Cohort 1 (i.e., 2 or more dose-limiting toxicities \[DLTs\]), then Cohort 2 of Part 1 will not be initiated and a dose of 150 mg BID of GSK2118436 will be administered in Part 2 of the study. In Cohort 2 six subjects will receive GSK2118436 300 mg BID on Study Days 1 to 7 and a single 300 mg dose on the morning of Day 8. Based on the safety data of subjects in Cohort 2 subjects will be enrolled in Part 2. If the 300 mg BID dose level of GSK2118436 is not well tolerated, then the highest tolerated dose will be selected for Part 2 of the study.

In Part 1 of the study the decision to proceed to the next cohort or Part 2 of the study will be based on the safety data of at least 6 evaluable subjects (\<=1 DLTs during the 14 days following the first dose of GSK2118436).

In Part 2 of the study eligible subjects will receive a single dose of GSK2118436/placebo (4 capsules of 75 mg/highest tolerated dose) orally on the first 2 days of the study followed by 2 doses daily for 6 days and a single dose on the 9th day. There will be 1 day when a placebo will be given.

In both the parts of the study serial blood samples for pharmacokinetic (PK) analysis for GSK2118436 and its metabolites (GSK2285403, GSK2298683 and GSK2167542) will be obtained at the same time points on the first and last day of dosing (2nd day of dosing also included for Part 2). Safety electrocardiogram (ECG)s will be performed at several timepoints during the study. In Part 2 Holter ECG monitoring will be performed for 24 hours on the 1st, 2nd and 9th days of dosing.

Conditions

Interventions

DRUG

GSK2118436 75 mg

Each capsule contains 75 mg of GSK2118436A as the mesylate salt, micronized particles as active equivalents.

DRUG

Placebo

Matching placebo capsules will be administered in Part 2 of the study.

Sponsors & Collaborators

Principal Investigators

  • GSK Clinical Trials · GlaxoSmithKline

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2013-01-22
Primary Completion
2014-11-28
Completion
2014-11-28

Countries

  • United States
  • Australia
  • United Kingdom

Study Locations

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Entities

Drugs
Diseases
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01738451 on ClinicalTrials.gov