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

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Long QT Syndrome

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02365532

GS-US-372-1666

Details and patient eligibility

About

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

Enrollment: 60 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Placebo to match GS-6615

Placebo Comparator group

Description:

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

Treatment:

Drug: Dofetilide

Drug: Placebo to match GS-6615

Drug: Placebo to match dofetilide

GS-6615

Experimental group

Description:

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

Treatment:

Drug: Dofetilide

Drug: Placebo to match GS-6615

Drug: Placebo to match dofetilide

Drug: GS-6615