A Study to Look at the Electrical Activity of the Heart in Subjects With Solid Tumor Cancers, Before and After Receiving the Study Treatment, GSK1120212

Cancer Clinical Trial

Official title: A Phase I, Single-Sequence, Placebo-Controlled, Single-Blind Study to Evaluate the Effect of Repeat Oral Dosing of GSK1120212 on Cardiac Repolarization in Subjects With Solid Tumors

Status Completed

Clinical Trial Summary

A multicenter, non-randomized, placebo-controlled, single dosing schedule, subject-blinded study to evaluate the effect of GSK1120212 on the electrical activity of the heart as compared to placebo in subjects with solid tumor cancers. All subjects will undergo Screening assessments within 21 days prior to the start of the study treatment to determine their eligibility for enrollment in the study. Eligible subjects will receive study treatment administered over a period of 15 days followed by a post-treatment follow-up visit. Study treatment (GSK1120212-matched placebo) will be blinded to subjects. Subjects will receive GSK1120212-matched placebo on one day during the first 14 days of dosing. On all other days the subject will receive a once-daily 2 mg dose of GSK1120212 except for Day 15 when the subject will receive 3mg dose of GSK1120212 12-lead ECG recordings will be obtained from continuous ECG recordings obtained via a 12-lead Holter monitor on Study Days 1 and 15 while subjects are in the clinical research unit. The effect of GSK1120212 on the electrical activity of the heart will be determined by time-matched ECGs obtained at the same time points relative to dosing on these days. Ambulatory blood pressure readings will be obtained from continuous 24-hour recordings via an ambulatory blood pressure monitor The effect of GSK1120212 on blood pressure parameters will be determined by blood pressure readings obtained at the same time points relative to dosing on Study Days 1 and 15. Serial blood samples to analyze the concentration of study drug in the subject's blood will be obtained at the same time points relative to dosing on Study Days 1 and 15. Subjects who are eligible for continued treatment with GSK1120212 may continue treatment under the rollover study MEK114375 (drug study number). A post-treatment follow-up visit will be conducted within 28 days of the last dose of study treatment for all subjects who do not continue treatment in the rollover study MEK114375.

Clinical Trial Description

GSK1120212 is an orally administered, potent and highly selective small molecule inhibitor of MEK1(mitogen-activated extracellular signal-regulated kinase-1)/MEK2 (mitogen-activated extracellular signal-regulated kinase-2) activation and kinase activity. As monotherapy, GSK1120212 has shown an acceptable risk-benefit profile with encouraging efficacy in various oncologic settings. This Phase I, single-sequence, placebo-controlled, singleblind, multicenter study is designed to evaluate the effects of repeat oral dosing of GSK1120212 on electrocardiographic parameters with a particular focus on its effect on cardiac repolarization (Corrected QT interval [QTc] duration) as compared to placebo in subjects with solid tumor cancers. A single dose of placebo will be administered on Study Day 1 followed by administration of a once-daily 2 mg dose of GSK1120212 for 13 days (Study Days 2 through 14) and on Study Day 15 a dose of 3 mg of GSK1120212 will be given. Digital 12-lead electrocardiograms (ECGs) will be extracted from continuous ECG recordings obtained via Holter monitor on Study Days 1 and 2 after the administration of placebo and on Study Days 15 and 16 after the administration of GSK1120212. Pharmacokinetic samples will be time-matched with the Holter ECGs. This study will also assess the exposure-QTc relationship between plasma concentrations of GSK1120212 and its effect, if any, on cardiac repolarization, specifically on the QTc interval. Continuous 24-hour ambulatory blood pressure monitoring will be conducted to assess the effect of GSK1120212 on blood pressure parameters on Study Days 1 and 15. Safety assessments, including assessment of adverse events, clinical laboratory tests (hematology and clinical chemistry) and vital signs, will be performed throughout the study. Following completion of study treatment, eligible subjects may transition to the open-label, rollover study MEK114375 to continue treatment with GSK1120212. ;

Related Conditions & MeSH terms

• Cancer

• NCT number: NCT01658553
• Study type: Interventional
• Source: GlaxoSmithKline
• Status: Completed
• Phase: Phase 1
• Start date: September 19, 2012
• Completion date: April 5, 2014