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Atrial FibrillationPhase 2HARMONYNCT01522651

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

A Phase 2 study testing Ranolazine and Dronedarone in people with Atrial Fibrillation, run by Gilead Sciences at 50 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation
What is being tested?
Ranolazine and Dronedarone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
134 participants
Where
50 sitesin 7 countries
Study dates
24 Jan 2012to 10 Mar 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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%
Show all 35Show fewer
  • 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
  • Need for concomitant treatment during the trial, with drugs or products that are strong inhibitors of cytochrome P450 3A (CYP3A), or inducers of CYP3A
  • Such medications should be discontinued 5-half lives prior to the Run-in period
  • Use of grapefruit juice or Seville orange juice during the study
  • Use of Class I and Class III antiarrhythmic drugs other than amiodarone within 5-half lives prior to the Run-in period
  • Use of amiodarone within 3 months prior to Screening
  • Use of drugs that prolong the QT interval
  • Previous use of ranolazine or dronedarone within 2 months prior to screening
  • Prior use of ranolazine or dronedarone which was discontinued for safety or tolerability
  • Use of dabigatran during the study
  • Use of digitalis preparations (eg, digoxin) during the study
  • Use of a greater than 1000 mg total daily dose of metformin during the study
  • Laboratory tests:
  • Hypokalemia (serum potassium < 3.5 mEq/L) at Screening that cannot be corrected to a level of potassium ≥ 3.5 mEq/L prior to randomization
  • Moderate and severe hepatic impairment (ie, Child-Pugh Class B and C), abnormal liver function test defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin > 2 x upper limit of normal (ULN) at Screening
  • Severe renal impairment defined as creatinine clearance ≤ 30 mL/min at Screening
  • Others:
  • Females who are pregnant or are breastfeeding
  • In the judgment of the Investigator, any clinically-significant ongoing medical condition that might jeopardize the individual's safety or interfere with the study, including participation in another clinical trial within the previous 30 days using a therapeutic modality which could have potential residual effects that might confound the results of this study
  • Any device-related technical issue which in the judgment of the investigator would disrupt adequate data collection or interpretation (eg, anticipated pulse generator change or lead revision)
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

50 sites in 7 countries.

50 sites in 7 countries

United States15 sites

  • Investigational Site

    Aurora, Colorado, 80012

  • Investigational Site

    Beverly Hills, California, 90211

  • Investigational Site

    Cleveland, Ohio, 44106

  • Investigational Site

    Houston, Texas, 77030

  • Investigational Site

    Lakeland, Florida, 33805

  • Investigational Site

    Murray, Utah, 84107

  • Investigational Site

    Newport Beach, California, 92663

  • Investigational Site

    San Francisco, California, 94143

  • Investigational Site

    Seattle, Washington, 98122

  • Investigational Site

    Takoma Park, Maryland, 20912

  • Investigational Site

    Towson, Maryland, 21204

  • Investigational Site

    Utica, New York, 13501

  • Investigational Site

    Warwick, Rhode Island, 02886

  • Investigational Site

    Washington D.C., District of Columbia, 20010

  • Investigational Site

    Wausau, Wisconsin, 54401

Other trials in United States

Poland14 sites

  • Investigational Site

    Bialystok, Podlaskie Voivodeship, 15-276

  • Investigational Site

    Gdansk, Pomeranian Voivodeship, 80-219

  • Investigational Site

    Katowice, Silesian Voivodeship, 40-635

  • Investigational Site

    Krakow, Lesser Poland Voivodeship, 31-501

  • Investigational Site

    Lodz, 91-425

  • Investigational Site

    Lodz, Łódź Voivodeship, 90-553

  • Investigational Site

    Poznan, Greater Poland Voivodeship, 61-848

  • Investigational Site

    Sopot, Pomeranian Voivodeship, 81-717

  • Investigational Site

    Szczecin, Zachodniop, 70-203

  • Investigational Site

    Torun, Kuyavian-Pomeranian Voivodeship, 87-100

  • Investigational Site

    Warsaw, Masovian Voivodeship, 01-211

  • Investigational Site

    Warsaw, Masovian Voivodeship, 04-628

  • Investigational Site

    Warsaw, 02-097

  • Investigational Site

    Zabrze, Silesian Voivodeship, 41-800

Other trials in Poland

Germany8 sites

  • Investigational Site

    Bonn, North Rhine-Westphalia, 53105

  • Investigational Site

    Coburg, 96450

  • Investigational Site

    Frankfurt, 60594

  • Investigational Site

    Göttingen, 37075

  • Investigational Site

    Ingolstadt, 85049

  • Investigational Site

    Lübeck, D23538

  • Investigational Site

    München, Bavaria, 81377

  • Investigational Site

    Würzburg, Bavaria, 97080

Other trials in Germany

Israel8 sites

  • Investigational Site

    Afula, Zefat, 18101

  • Investigational Site

    Ashkelon, Ashqelon, 78287

  • Investigational Site

    Hadera, 38100

  • Investigational Site

    Haifa, 31096

  • Investigational Site

    Holon, 58100

  • Investigational Site

    Jerusalem, 91031

  • Investigational Site

    Nahariya, 22100

  • Investigational Site

    Rehovot, 76100

Other trials in Israel

Italy2 sites

  • Investigational Site

    Como, 22020

  • Investigational Site

    Florence, 50134

Other trials in Italy

Netherlands2 sites

  • Investigational Site

    Groningen, 9700 RB

  • Investigational Site

    Maastricht, Limburg, 6229 HX

Other trials in Netherlands

United Kingdom1 site

  • Investigational Site

    London, England, SE5 9RS

Other trials in United Kingdom

About this study

Official title: A Phase 2, Proof of Concept, Randomized, Placebo-Controlled, Parallel Group Study to Evaluate the Effect of Ranolazine and Dronedarone When Given Alone and in Combination on Atrial Fibrillation Burden in Subjects With Paroxysmal Atrial Fibrillation

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.

Being tested
Ranolazine, Dronedarone, Ranolazine placebo, Dronedarone placebo
Keywords
Atrial Fibrillation, Ranolazine, Dronedarone, Dual Chamber Pacemakers
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RanolazineDrug

    Also called Ranexa®

    Tablets administered orally twice daily.

  • DronedaroneDrug

    Capsule administered orally twice daily

  • Ranolazine placeboDrug

    Tablets administered orally twice daily.

  • Dronedarone placeboDrug

    Capsules administered orally twice daily

Study groups in NCT01522651
Study groupRoleWhat they receive
PlaceboPlacebo comparatorRanolazine placebo plus dronedarone placebo for 12 weeks.
Receives: Drug: Ranolazine placebo; Drug: Dronedarone placebo
Ranolazine 750 mgExperimentalRanolazine 750 mg plus dronedarone placebo for 12 weeks.
Receives: Drug: Ranolazine; Drug: Dronedarone placebo
Dronedarone 225 mgExperimentalRanolazine placebo plus dronedarone 225 mg for 12 weeks.
Receives: Drug: Dronedarone; Drug: Ranolazine placebo
Ranolazine 750 mg + Dronedarone 225 mgExperimentalRanolazine 750 mg plus dronedarone 225 mg for 12 weeks.
Receives: Drug: Ranolazine; Drug: Dronedarone
Ranolazine 750 mg + Dronedarone 150 mgExperimentalRanolazine 750 mg plus dronedarone 150 mg for 12 weeks.
Receives: Drug: Ranolazine; Drug: Dronedarone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline

  2. 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.

    Measured: Baseline; Week 12

  3. 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.

    Measured: Baseline; Week 12

Secondary outcomes (1)

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

    AFB was defined as the total time a participant was in AT/AF expressed as a percentage of total recording time.

    Measured: Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2012 (estimated)
  2. Study start24 Jan 2012
  3. Primary completion10 Mar 2014
  4. Study completion10 Mar 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01522651
Sponsor's protocol ID
GS-US-291-0102
Other IDs
2011-001134-42
Acronym
HARMONY
Status last verified
Sep 2020
First submitted
18 Jan 2012
Last updated
6 Nov 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 26226999

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ranolazine and Dronedarone in people with Atrial Fibrillation, run by Gilead Sciences at 50 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in United States, Poland, Germany, Israel, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Atrial Fibrillation Burden (AFB) at Baseline (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01522651, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2020.

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