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

Phase 1

Completed

• Conditions: Long QT Syndrome
• Interventions: Drug: Placebo to match GS-6615; Drug: GS-6615; Drug: Placebo to match dofetilide; Drug: Dofetilide

• Registration Number: NCT02365532
• Lead Sponsor: Gilead Sciences

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-02-13
• Study First Submitted QC: 2015-02-13
• Study First Posted: 2015-02-19
• Status Verified: 2015-05
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Last Update Submitted: 2015-05-19
• Last Update Posted: 2015-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo to match GS-6615	Placebo to match GS-6615	Placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
Placebo to match GS-6615	Placebo to match dofetilide	Placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
GS-6615	Placebo to match GS-6615	GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
GS-6615	GS-6615	GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
GS-6615	Placebo to match dofetilide	GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
Placebo to match GS-6615	Dofetilide	Placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
GS-6615	Dofetilide	GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily

Primary Outcome Measures

Name	Time	Method
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	Predose and postdose on Days -2 through Day 4	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Spaulding Clinical Research, LLC; 🇺🇸 West Bend, Wisconsin, United States