Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Subjects

This study will evaluate the effect of oral GS-6615 on QTc interval in healthy adults with dofetilide-induced QTc prolongation.

Study Overview

• Status: Completed
• Conditions: Long QT Syndrome
• Intervention / Treatment: Drug: Placebo to match GS-6615; Drug: Placebo to match dofetilide; Drug: Dofetilide; Drug: GS-6615

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs
• Have a calculated body mass index (BMI) from 18 to 30 kg/m^2, inclusive, at study screening
• Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant and which do not interfere with the ability to interpret the QT interval in the opinion of the investigator in consultation with the medical monitor

Exclusion Criteria:

• History of meningitis or encephalitis, epilepsy, seizures (known or suspected), migraines, tremors, myoclonic jerks, sleep disorder, anxiety, syncope, head injuries, or a family history of seizures
• Have any serious or active medical or psychiatric illness (including depression) which, in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment.
• Presence or history of cardiovascular disease, including structural heart disease, myocardial infarction (by ECG and/or clinical history), history of ventricular tachycardia or torsade de pointes, heart failure or cardiomyopathy (by clinical history and/or left ventricular ejection fraction < 40%), presence of cardiac conduction abnormalities, a family history of Long QT or Brugada Syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years

• Additional cardiovascular-specific exclusion criteria include findings on screening ECG of:

  • QTcF interval > 430 msec
  • PR interval > 220 msec
  • QRS duration > 110 msec
  • Second- or third-degree atrioventricular block
  • Complete left or right bundle branch block or incomplete right bundle branch block
  • Resting heart rate < 40 or > 100 beats per minute (bpm)
  • Pathological Q waves (defined as Q wave > 40 msec)
  • Ventricular pre-excitation
  • More than 2 ectopic beats
• Syncope, palpitations, or unexplained dizziness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo to match GS-6615; Placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily	Drug: Placebo to match GS-6615; Placebo to match GS-6615 tablets administered orally; Drug: Placebo to match dofetilide; Placebo to match dofetilide capsules administered orally; Drug: Dofetilide; Dofetilide 500 μg capsules administered orally according to the current prescribing information
Experimental: GS-6615; GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily	Drug: Placebo to match GS-6615; Placebo to match GS-6615 tablets administered orally; Drug: Placebo to match dofetilide; Placebo to match dofetilide capsules administered orally; Drug: Dofetilide; Dofetilide 500 μg capsules administered orally according to the current prescribing information; Drug: GS-6615; GS-6615 tablets administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in daytime QT interval corrected for heart rate using the Fridericia formula (QTcF)		Up to 6 days
Pharmacokinetic (PK) profiles of GS-6615 and dofetilide	This endpoint will measure the plasma PK profiles of GS-6615 and dofetilide. PK parameters that will be measured include Cmax, Tmax, AUC_0-24, and AUC_0-tlast.	Predose and postdose on Days -2 through Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events, clinical laboratory test results, vital sign measurements, and electrocardiogram (ECG) data	This endpoint will measure the safety and tolerability profile of GS-6615.	Up to 6 days

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Kimberly B Patel, MD, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: February 13, 2015
• First Submitted That Met QC Criteria: February 13, 2015
• First Posted (Estimate): February 19, 2015

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 19, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: drug-induced long QT syndrome; DILQTS; prolonged QT
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Long QT Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Membrane Transport Modulators; Potassium Channel Blockers; Dofetilide
• Other Study ID Numbers: GS-US-372-1666