Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients

NCT01648205 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IN-US-259-0128
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether late sodium channel blockade might be effective in shortening the QTc interval in various LQT3 mutations and be considered as a safe therapeutic option for LQT3 patients.

Conditions

Long QT Syndrome

Keywords

ranolazine; clinical trial

Outcome Measures

Primary Outcomes (1)

• Change in QTc Duration at 2 Months

  Change in QTc at 2 months on ranolazine vs. at 1 month on placebo. This was prespecified outcome.

  1 month to 2 months

Secondary Outcomes (1)

• Change in QTc at 6 Months

  1 month to 6 months

Study Arms (1)

Placebo followed by Ranolazine Administration

EXPERIMENTAL

Placebo for 1 month and Ranolazine for 5 months.

Drug: Placebo; Drug: Ranolazine

Interventions

Placebo DRUG

Matching Placebo will be given for first month.

Placebo followed by Ranolazine Administration

Ranolazine DRUG

Patients will receive ranolazine 1000mg bid for subsequent 5 months.

Also known as: Ranexa

Placebo followed by Ranolazine Administration

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Genotyped positive for LQT3 (SCN5A) mutation
• Age 21 years or older
• Not currently taking an antiarrhythmic drug (beta blockers are allowed)
• Enrolled in LQTS Registry

You may not qualify if:

• Age less than 21 years
• Not confirmed to have an LQT3 mutation
• Significant co-morbidity that would preclude subject's safe participation in this study
• Females who are pregnant or nursing
• Females of childbearing age who are not using acceptable method of birth control
• Evidence of prior sensitivity to ranolazine
• Hepatic or renal disease that might adversely affect ranolazine excretion
• Currently taking strong CYP3A inhibitors
• Currently taking P-gp inhibitors
• Currently taking CYP3A inducers
• In vitro studies of specific mutation show no effect of ranolazine on late sodium current kinetics or show repolarization prolongation

Sponsors & Collaborators

• University of Rochester: lead
• Gilead Sciences: collaborator

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

Related Publications (5)

• Moss AJ, Zareba W, Schwarz KQ, Rosero S, McNitt S, Robinson JL. Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol. 2008 Dec;19(12):1289-93. doi: 10.1111/j.1540-8167.2008.01246.x. Epub 2008 Jul 25.

  PMID: 18662191 BACKGROUND

• Zareba W, Moss AJ, Schwartz PJ, Vincent GM, Robinson JL, Priori SG, Benhorin J, Locati EH, Towbin JA, Keating MT, Lehmann MH, Hall WJ. Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med. 1998 Oct 1;339(14):960-5. doi: 10.1056/NEJM199810013391404.

  PMID: 9753711 BACKGROUND

• Zareba W, Moss AJ, Locati EH, Lehmann MH, Peterson DR, Hall WJ, Schwartz PJ, Vincent GM, Priori SG, Benhorin J, Towbin JA, Robinson JL, Andrews ML, Napolitano C, Timothy K, Zhang L, Medina A; International Long QT Syndrome Registry. Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J Am Coll Cardiol. 2003 Jul 2;42(1):103-9. doi: 10.1016/s0735-1097(03)00554-0.

  PMID: 12849668 BACKGROUND

• Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantu F, Towbin JA, Keating MT, Hammoude H, Brown AM, Chen LS, Colatsky TJ. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation. 1995 Dec 15;92(12):3381-6. doi: 10.1161/01.cir.92.12.3381.

  PMID: 8521555 BACKGROUND

• Benhorin J, Taub R, Goldmit M, Kerem B, Kass RS, Windman I, Medina A. Effects of flecainide in patients with new SCN5A mutation: mutation-specific therapy for long-QT syndrome? Circulation. 2000 Apr 11;101(14):1698-706. doi: 10.1161/01.cir.101.14.1698.

  PMID: 10758053 BACKGROUND

MeSH Terms

Conditions

Long QT Syndrome

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Wojciech Zareba, MD, PhD
• Organization: University of Rochester

wojciech_zareba@urmc.rochester.edu

5852755391

Study Officials

• Wojciech Zareba, MD,PhD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Matching placebo and ranolazine pills were used. Patients were blinded regarding administration of medication. ECG Core Lab reading ECGs was blinded regarding drug assignment.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Patients will receive placebo for 1 month and subsequently ranolazine 1000mg twice a day for 5 months.

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 24, 2012
• Study Start: September 1, 2012
• Primary Completion: July 20, 2018
• Study Completion: July 20, 2018
• Last Updated: April 7, 2022
• Results First Posted: April 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)