Study to Evaluate the Effect of Eleclazine on QT, Safety, and Tolerability in Participants With Long QT2 Syndrome

NCT02365506 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GS-US-394-1658
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to evaluate the effect of oral eleclazine (formerly GS-6615) on corrected QT (QTc) interval in participants with long QT2 syndrome.

Conditions

LQT2 Syndrome

Keywords

Congenital Long QT Syndrome; LQTS; Sudden Cardiac Death

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Standard 12-Lead Electrocardiogram (ECG) Daytime QT Interval Corrected For Heart Rate Using The Fridericia Formula (QTcF) (AUC0-8)/8 at Day 3: Lead V5

  Daytime (AUC0-8)/8 was defined as the area under the QTc curve during the 8 hours postdose, where 0 was defined as the time of dosing (i.e., T = 0) on a given day. Daytime (AUC0-8)/8 was computed by dividing AUC0-8 by the time from dosing to the 8 hour postdose time point. QTcF is corrected QT interval using Fridericia's formula.

  Baseline (Day 1), Day 3

• Change From Baseline in Standard 12-Lead ECG Daytime QTcF (AUC0-8)/8 at Day 3: Lead II

  Daytime (AUC0-8)/8 was defined as the area under the QTc curve during the 8 hours postdose, where 0 was defined as the time of dosing (i.e.,T = 0) on a given day. Daytime (AUC0-8)/8 was computed by dividing AUC0-8 by the time from dosing to the 8 hour postdose time point. QTcF is corrected QT interval using Fridericia's formula.

  Baseline (Day 1), Day 3

• Change From Baseline in Standard 12-Lead ECG Daytime QTcF (AUC0-8)/8 at Day 3: Global Lead

  Daytime (AUC0-8)/8 was defined as the area under the QTc curve during the 8 hours postdose, where 0 was defined as the time of dosing (i.e., T = 0) on a given day. Daytime (AUC0-8)/8 was computed by dividing AUC0-8 by the time from dosing to the 8 hour postdose time point. QTcF is corrected QT interval using Fridericia's formula.

  Baseline (Day 1), Day 3

Secondary Outcomes (5)

• Change From Baseline in Holter Daily QTcF Interval (Daytime and Nocturnal) at Day 3 : Lead V5

  Baseline (Day 1), Day 3

• Change From Baseline in Holter Daily QTcF Interval (Daytime and Nocturnal) at Day 3 : Global Lead

  Baseline (Day 1), Day 3

• Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Lead V5

  Predose, Days 2 and 3

• Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Lead II

  Predose, Days 2 and 3

• Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Global Lead

  Predose, Days 2 and 3

Study Arms (3)

Eleclazine 24 mg + Eleclazine 48 mg + Placebo

EXPERIMENTAL

Participants will receive placebo to match eleclazine on Days 1 and 4, eleclazine 24 mg on Day 2 and eleclazine 48 mg on Day 3.

Drug: Eleclazine; Drug: Placebo

Eleclazine 48 mg + Placebo

EXPERIMENTAL

Participants will receive placebo to match eleclazine on Days 1, 2 and 4, and eleclazine 48 mg on Day 3.

Drug: Eleclazine; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Participants will receive placebo to match eleclazine on Days 1 to 4.

Drug: Placebo

Interventions

Eleclazine DRUG

Tablets administered orally in a single dose

Also known as: GS-6615

Eleclazine 24 mg + Eleclazine 48 mg + Placebo; Eleclazine 48 mg + Placebo

Placebo DRUG

Placebo to match tablets administered orally in a single dose

Eleclazine 24 mg + Eleclazine 48 mg + Placebo; Eleclazine 48 mg + Placebo; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with an established diagnosis of LQT2 (by genotype testing)
• Mean (of triplicate) QTc interval ≥ 480 msec for at least four out of seven time points, determined by standard 12-lead electrocardiogram (ECG), at screening

You may not qualify if:

• Known mutations associated with long QT syndrome type 1 or long QT syndrome type 3
• Known or suspected history of seizures or epilepsy
• History of heart failure defined as New York Heart Association (NYHA) Class IV and/or known left ventricular ejection fraction (EF) ≤ 45%
• Body mass index (BMI) ≥ 36 kg/m\^2 at screening
• Severe renal impairment at screening (defined as an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m\^2, using the 4 variable modification of diet in renal disease (MDRD) equation), as determined by the study center
• Abnormal liver function tests at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 x upper limit of normal (ULN), or total bilirubin \> 1.5 x ULN
• An aborted cardiac arrest (ACA), implantable cardioverter-defibrillator (ICD) implantation, syncopal episode, or appropriate ICD therapy within 3 months prior to screening
• Any other condition or circumstance that in the opinion of the investigator would preclude compliance with the study protocol.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

University of Rochester Medical Center/Strong Memorial Hospital

Rochester, New York, 14620, United States

Location

MeSH Terms

Conditions

Long Qt Syndrome 2; Death, Sudden, Cardiac

Interventions

eleclazine

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Cardiovascular Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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 12, 2015
• First Posted: February 19, 2015
• Study Start: July 20, 2015
• Primary Completion: May 13, 2016
• Study Completion: June 13, 2016
• Last Updated: December 30, 2020
• Results First Posted: December 30, 2020

Record last verified: 2020-12

Locations

US (1)