Clinical trial NCT02365532: Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Long QT Syndrome
Keywords: drug-induced long QT syndrome
DILQTS
prolonged QT
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-02-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in daytime QT interval corrected for heart rate using the Fridericia formula (QTcF)
timeFrame: Up to 6 days
measure: Pharmacokinetic (PK) profiles of GS-6615 and dofetilide
timeFrame: Predose and postdose on Days -2 through Day 4
Secondary outcomes:
measure: Incidence of adverse events, clinical laboratory test results, vital sign measurements, and electrocardiogram (ECG) data
timeFrame: Up to 6 days
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Spaulding Clinical Research, LLC
state: Wisconsin
Study officials:
affiliation: Gilead Sciences
name: Kimberly B Patel, MD
role: STUDY_DIRECTOR
References: