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

NCT02365532 | Completed Phase 1

• 1 other identifier: GS-US-372-1666
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Long QT Syndrome

Keywords

drug-induced long QT syndrome; DILQTS; prolonged QT

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Incidence of adverse events, clinical laboratory test results, vital sign measurements, and electrocardiogram (ECG) data

  Up to 6 days

Study Arms (2)

Placebo to match GS-6615

PLACEBO COMPARATOR

Placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily

Drug: Placebo to match GS-6615; Drug: Placebo to match dofetilide; Drug: Dofetilide

GS-6615

EXPERIMENTAL

GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily

Drug: GS-6615; Drug: Placebo to match GS-6615; Drug: Placebo to match dofetilide; Drug: Dofetilide

Interventions

GS-6615 DRUG

GS-6615 tablets administered orally

GS-6615

Placebo to match GS-6615 DRUG

Placebo to match GS-6615 tablets administered orally

GS-6615; Placebo to match GS-6615

Placebo to match dofetilide DRUG

Placebo to match dofetilide capsules administered orally

GS-6615; Placebo to match GS-6615

Dofetilide DRUG

Dofetilide 500 μg capsules administered orally according to the current prescribing information

GS-6615; Placebo to match GS-6615

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Spaulding Clinical Research, LLC

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Conditions

Long QT Syndrome

Interventions

eleclazine; dofetilide

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kimberly B Patel, MD

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 19, 2015
• Study Start: February 1, 2015
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 20, 2015

Record last verified: 2015-05

Locations

US (1)