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

Long QT Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02365532
• Other study ID #: GS-US-372-1666
• Status: Completed
• Phase: Phase 1
• First received: February 13, 2015
• Last updated: May 19, 2015
• Start date: February 2015
• Est. completion date: May 2015

Study information

• Verified date: May 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Long QT Syndrome

Intervention

Drug:
• GS-6615
GS-6615 tablets administered orally
• Placebo to match GS-6615
Placebo to match GS-6615 tablets administered orally
• Placebo to match dofetilide
Placebo to match dofetilide capsules administered orally
• Dofetilide
Dofetilide 500 µg capsules administered orally according to the current prescribing information

Locations

Country	Name	City	State
United States	Spaulding Clinical Research, LLC	West Bend	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in daytime QT interval corrected for heart rate using the Fridericia formula (QTcF)		Up to 6 days	No
Primary	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	No
Secondary	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	No