Study to Evaluate the Effect of Ranolazine and Dronedarone When Given Alone and in Combination in Patients With Paroxysmal Atrial Fibrillation

NCT01522651 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: GS-US-291-01022011-001134-42
• Study Type: interventional
• Target: 134
• Locations: 7 countries
• Sites: 50

Brief Summary

The primary objective of this study is to evaluate the effect of ranolazine and of low-dose dronedarone when given alone and in combination at different dose levels on atrial fibrillation burden (AFB) over 12 weeks of treatment. AFB is defined as the total time a participant is in atrial tachycardia/atrial fibrillation (AT/AF) expressed as a percentage of total recording time.

Conditions

Atrial Fibrillation

Keywords

Atrial Fibrillation; Ranolazine; Dronedarone; Dual Chamber Pacemakers

Outcome Measures

Primary Outcomes (3)

• Atrial Fibrillation Burden (AFB) at Baseline

  AFB was defined as the total time a participant was in atrial tachycardia (AT)/atrial fibrillation (AF) expressed as a percentage of total recording time. Geometric mean is the mean of log-transformed AFB exponentiated.

  Baseline

• Percent Change From Baseline in Atrial Fibrillation Burden (AFB) by Week 12

  AFB was defined as the total time a participant was in atrial tachycardia (AT)/atrial fibrillation (AF) expressed as a percentage of total recording time. Data are presented for baseline-adjusted AFB over 12 weeks of treatment. Geometric mean is the mean of log-transformed AFB exponentiated.

  Baseline; Week 12

• Absolute Change From Baseline in AFB by Week 12

  AFB is defined as the total time a participant is in AT/AF expressed as a percentage of total recording time. Data are presented for baseline-adjusted AFB over 12 weeks of treatment.

  Baseline; Week 12

Secondary Outcomes (1)

• Percentage of Participants Who Had ≥ 30%, ≥ 50%, or ≥ 70% Reduction From Baseline in AFB

  Week 12

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Ranolazine placebo plus dronedarone placebo for 12 weeks.

Drug: Ranolazine placebo; Drug: Dronedarone placebo

Ranolazine 750 mg

EXPERIMENTAL

Ranolazine 750 mg plus dronedarone placebo for 12 weeks.

Drug: Ranolazine; Drug: Dronedarone placebo

Dronedarone 225 mg

EXPERIMENTAL

Ranolazine placebo plus dronedarone 225 mg for 12 weeks.

Drug: Dronedarone; Drug: Ranolazine placebo

Ranolazine 750 mg + Dronedarone 225 mg

EXPERIMENTAL

Ranolazine 750 mg plus dronedarone 225 mg for 12 weeks.

Drug: Ranolazine; Drug: Dronedarone

Ranolazine 750 mg + Dronedarone 150 mg

EXPERIMENTAL

Ranolazine 750 mg plus dronedarone 150 mg for 12 weeks.

Drug: Ranolazine; Drug: Dronedarone

Interventions

Ranolazine DRUG

Tablets administered orally twice daily.

Also known as: Ranexa®

Ranolazine 750 mg; Ranolazine 750 mg + Dronedarone 150 mg; Ranolazine 750 mg + Dronedarone 225 mg

Dronedarone DRUG

Capsule administered orally twice daily

Dronedarone 225 mg; Ranolazine 750 mg + Dronedarone 150 mg; Ranolazine 750 mg + Dronedarone 225 mg

Ranolazine placebo DRUG

Tablets administered orally twice daily.

Dronedarone 225 mg; Placebo

Dronedarone placebo DRUG

Capsules administered orally twice daily

Placebo; Ranolazine 750 mg

Eligibility Criteria

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

You may qualify if:

• Males and females aged 18 years and older
• Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• History of PAF documented within the prior 12 months
• \- Patients with PAF undergoing cardioversion greater than 4 weeks prior to Screening are eligible
• Implanted (at least 3 months prior to Screening) dual chamber programmable pacemakers with AF detection capabilities
• AFB ≥ 1% and ≤ 70% between the last clinic evaluation and Screening (minimum of 1 month observation period) and AFB ≥ 2% and ≤ 70% during the Run in period
• Sexually active females of childbearing potential must agree to utilize effective methods of contraception during heterosexual intercourse throughout the treatment period and for 14 days following discontinuation of the study medication

You may not qualify if:

• Disease - specific:
• Persistent AF or Permanent AF
• History of atrial flutter or atrial tachycardia without successful ablation
• Other acutely reversible causes of AF, including but not limited to: hyperthyroidism, pericarditis, myocarditis, or pulmonary embolism
• New York Heart Association (NYHA) Class III and IV heart failure or NYHA Class II heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic within 4 weeks prior to Screening.
• Recent history of left ventricular ejection fraction (LVEF) \< 40%
• Myocardial infarction, unstable angina, or coronary artery bypass graft (CABG) surgery within three months prior to Screening or percutaneous coronary intervention (PCI) within 4 weeks prior to Screening
• Clinically significant valvular disease in the opinion of the Investigator
• Stroke within 3 months prior to Screening
• History of serious ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation) within 4 weeks prior to Screening
• Family history of long QT syndrome
• Corrected QT interval (QTc) ≥ 500 msec (Bazett) at Screening ECG if in sinus rhythm (SR). If in AF, evidence of QTc ≥ 500 msec (Bazett) within 4 weeks prior to Screening
• Prior heart transplant
• Cardiac ablation within 4 months prior to Screening, or planned ablation during the course of the study
• Concomitant medications/food

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (50)

Investigational Site

Beverly Hills, California, 90211, United States

Location

Investigational Site

Newport Beach, California, 92663, United States

Location

Investigational Site

San Francisco, California, 94143, United States

Location

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Aurora, Colorado, 80012, United States

Location

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Washington D.C., District of Columbia, 20010, United States

Location

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Lakeland, Florida, 33805, United States

Location

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Takoma Park, Maryland, 20912, United States

Location

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Towson, Maryland, 21204, United States

Location

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Utica, New York, 13501, United States

Location

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Cleveland, Ohio, 44106, United States

Location

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Warwick, Rhode Island, 02886, United States

Location

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Houston, Texas, 77030, United States

Location

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Murray, Utah, 84107, United States

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Seattle, Washington, 98122, United States

Location

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Wausau, Wisconsin, 54401, United States

Location

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München, Bavaria, 81377, Germany

Location

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Würzburg, Bavaria, 97080, Germany

Location

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Bonn, North Rhine-Westphalia, 53105, Germany

Location

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Coburg, 96450, Germany

Location

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Frankfurt, 60594, Germany

Location

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Göttingen, 37075, Germany

Location

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Ingolstadt, 85049, Germany

Location

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Lübeck, D23538, Germany

Location

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Ashkelon, Ashqelon, 78287, Israel

Location

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Afula, Zefat, 18101, Israel

Location

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Hadera, 38100, Israel

Location

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Haifa, 31096, Israel

Location

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Holon, 58100, Israel

Location

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Jerusalem, 91031, Israel

Location

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Nahariya, 22100, Israel

Location

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Rehovot, 76100, Israel

Location

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Como, 22020, Italy

Location

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Florence, 50134, Italy

Location

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Maastricht, Limburg, 6229 HX, Netherlands

Location

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Groningen, 9700 RB, Netherlands

Location

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Poznan, Greater Poland Voivodeship, 61-848, Poland

Location

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Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

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Krakow, Lesser Poland Voivodeship, 31-501, Poland

Location

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Warsaw, Masovian Voivodeship, 01-211, Poland

Location

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Warsaw, Masovian Voivodeship, 04-628, Poland

Location

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Bialystok, Podlaskie Voivodeship, 15-276, Poland

Location

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Gdansk, Pomeranian Voivodeship, 80-219, Poland

Location

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Sopot, Pomeranian Voivodeship, 81-717, Poland

Location

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Katowice, Silesian Voivodeship, 40-635, Poland

Location

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Zabrze, Silesian Voivodeship, 41-800, Poland

Location

Investigational Site

Szczecin, Zachodniop, 70-203, Poland

Location

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Lodz, 91-425, Poland

Location

Investigational Site

Warsaw, 02-097, Poland

Location

Investigational Site

Lodz, Łódź Voivodeship, 90-553, Poland

Location

Investigational Site

London, England, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Reiffel JA, Camm AJ, Belardinelli L, Zeng D, Karwatowska-Prokopczuk E, Olmsted A, Zareba W, Rosero S, Kowey P; HARMONY Investigators. The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism. Circ Arrhythm Electrophysiol. 2015 Oct;8(5):1048-56. doi: 10.1161/CIRCEP.115.002856. Epub 2015 Jul 30.

  PMID: 26226999 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Ranolazine; Dronedarone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; 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; Amiodarone; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2012
• First Posted: January 31, 2012
• Study Start: January 24, 2012
• Primary Completion: March 10, 2014
• Study Completion: March 10, 2014
• Last Updated: November 6, 2020
• Results First Posted: November 6, 2020

Record last verified: 2020-09

Locations

GB (1); US (15); DE (8); IL (8); NL (2); PL (14); IT (2)