Ignite Creation Date:
2024-05-06 @ 1:07 AM
Last Modification Date:
2024-10-26 @ 10:59 AM
Study NCT ID:
NCT01738451
Status:
COMPLETED
Last Update Posted:
2017-11-13
First Post:
2012-11-15
Brief Title:
A Study to Evaluate the Effect of Repeat Oral Dosing of GSK2118436 on Cardiac Repolarization in Subjects With V600 BRAF Mutation-Positive Tumors
Sponsor:
GlaxoSmithKline
Organization:
GlaxoSmithKline
Study Overview
Official Title:
A Two-Part Study to Evaluate the Effect of Repeat Oral Dosing of GSK2118436 on Cardiac Repolarization in Subjects With V600 BRAF Mutation-Positive Tumors An Open-label Dose-escalating Safety Lead-in Study Followed by a Single-sequence Placebo-controlled Single-blind Study
Status:
COMPLETED
Status Verified Date:
2017-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 ie 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 GSK2118436placebo 4 capsules of 75 mghighest 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 ECGs 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
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 ie 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 GSK2118436placebo 4 capsules of 75 mghighest 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 ECGs 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None