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

Last updated: November 4, 2020
Sponsor: Gilead Sciences
Overall Status: Completed

Phase

2

Condition

Atrial Fibrillation

Arrhythmia

Chest Pain

Treatment

N/A

Clinical Study ID

NCT01522651
GS-US-291-0102
2011-001134-42
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Key Inclusion Criteria:

  • Males and females aged 18 years and older
  • Have the ability to understand and sign a written informed consent form, which must beobtained 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 Screeningare eligible
  • Implanted (at least 3 months prior to Screening) dual chamber programmable pacemakerswith AF detection capabilities
  • AFB ≥ 1% and ≤ 70% between the last clinic evaluation and Screening (minimum of 1month observation period) and AFB ≥ 2% and ≤ 70% during the Run in period
  • Sexually active females of childbearing potential must agree to utilize effectivemethods of contraception during heterosexual intercourse throughout the treatmentperiod and for 14 days following discontinuation of the study medication

Exclusion

Key Exclusion Criteria: 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 IIheart failure with a recent decompensation requiring hospitalization or referral to aspecialized 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) surgerywithin 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 thecourse of the study Concomitant medications/food
  • Need for concomitant treatment during the trial, with drugs or products that arestrong 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-halflives 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 ortolerability
  • 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 alevel of potassium ≥ 3.5 mEq/L prior to randomization
  • Moderate and severe hepatic impairment (ie, Child-Pugh Class B and C), abnormal liverfunction 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 medicalcondition that might jeopardize the individual's safety or interfere with the study,including participation in another clinical trial within the previous 30 days using atherapeutic modality which could have potential residual effects that might confoundthe results of this study
  • Any device-related technical issue which in the judgment of the investigator woulddisrupt adequate data collection or interpretation (eg, anticipated pulse generatorchange or lead revision) Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Total Participants: 134
Study Start date:
January 24, 2012
Estimated Completion Date:
March 10, 2014

Connect with a study center

  • Investigational Site

    Erlangen, Bayern 91054
    Germany

    Site Not Available

  • Investigational Site

    München, Bayern 81377
    Germany

    Site Not Available

  • Investigational Site

    Weiden, Bayern 92637
    Germany

    Site Not Available

  • Investigational Site

    Würzburg, Bayern 97080
    Germany

    Site Not Available

  • Investigational Site

    Wiesbaden, Hessen 65191
    Germany

    Site Not Available

  • Investigational Site

    Bielefeld, Nordrhein-westfalen 33604
    Germany

    Site Not Available

  • Investigational Site

    Bonn, Nordrhein-westfalen 53105
    Germany

    Site Not Available

  • Investigational Site

    Dortmund, Nordrhein-westfalen 44137
    Germany

    Site Not Available

  • Investigational Site

    Coburg, 96450
    Germany

    Site Not Available

  • Investigational Site

    Frankfurt, 60594
    Germany

    Site Not Available

  • Investigational Site

    Goettingen, 37075
    Germany

    Site Not Available

  • Investigational Site

    Göttingen, 37075
    Germany

    Site Not Available

  • Investigational Site

    Hamburg, 20246
    Germany

    Site Not Available

  • Investigational Site

    Ingolstadt, 85049
    Germany

    Site Not Available

  • Investigational Site

    Lubeck, D23538
    Germany

    Site Not Available

  • Investigational Site

    Ashkelon, Ashqelon 78287
    Israel

    Site Not Available

  • Investigational Site

    Afula, Zefat 18101
    Israel

    Site Not Available

  • Investigational Site

    Hadera, 38100
    Israel

    Site Not Available

  • Investigational Site

    Haifa, 31096
    Israel

    Site Not Available

  • Investigational Site

    Holon, 58100
    Israel

    Site Not Available

  • Investigational Site

    Jerusalem, 91031
    Israel

    Site Not Available

  • Investigational Site

    Nahariya, 22100
    Israel

    Site Not Available

  • Investigational Site

    Petach Tikva, 49100
    Israel

    Site Not Available

  • Investigational Site

    Ramat Gan, 52621
    Israel

    Site Not Available

  • Investigational Site

    Rehovot, 76100
    Israel

    Site Not Available

  • Investigational Site

    Tel Aviv, 64239
    Israel

    Site Not Available

  • Investigational Site

    Tel Hashomer, 52621
    Israel

    Site Not Available

  • Investigational Site

    Bologna, 40138
    Italy

    Site Not Available

  • Investigational Site

    Como, 22020
    Italy

    Site Not Available

  • Investigational Site

    Firenze, 50134
    Italy

    Site Not Available

  • Investigational Site

    Maastricht, Limburg 6229 HX
    Netherlands

    Site Not Available

  • Investigational Site

    Groningen, 9700 RB
    Netherlands

    Site Not Available

  • Investigational Site

    Torun, Kujawsko-pomorskie 87-100
    Poland

    Site Not Available

  • Investigational Site

    Lódz, Lodzkie 90-553
    Poland

    Site Not Available

  • Investigational Site

    Lódz, Lodzkie 90-553
    Poland

    Site Not Available

  • Investigational Site

    Kraków, Malopolskie 31-501
    Poland

    Site Not Available

  • Investigational Site

    Kraków, Malopolskie 31-501
    Poland

    Site Not Available

  • Investigational Site

    Warsaw, Mazowieckie 01-211
    Poland

    Site Not Available

  • Investigational Site

    Bialystok, Podlaskie 15-276
    Poland

    Site Not Available

  • Investigational Site

    Gdansk, Pomorskie 80-219
    Poland

    Site Not Available

  • Investigational Site

    Sopot, Pomorskie 81-717
    Poland

    Site Not Available

  • Investigational Site

    Katowice, Slaskie 40-635
    Poland

    Site Not Available

  • Investigational Site

    Zabrze, Slaskie 41-800
    Poland

    Site Not Available

  • Investigational Site

    Posnan, Wielkopolskie 61-848
    Poland

    Site Not Available

  • Investigational Site

    Poznań, Wielkopolskie 61-848
    Poland

    Site Not Available

  • Investigational Site

    Szczecin, Zachodniop 70-203
    Poland

    Site Not Available

  • Investigational Site

    Lodz, 91-425
    Poland

    Site Not Available

  • Investigational Site

    Warszawa, 02-097
    Poland

    Site Not Available

  • Investigational Site

    London, England SE5 9RS
    United Kingdom

    Site Not Available

  • Investigational Site

    Cardiff, Wales CF14 4XW
    United Kingdom

    Site Not Available

  • Investigational Site

    Phoenix, Arizona 85013
    United States

    Site Not Available

  • Investigational Site

    Beverly Hills, California 90211
    United States

    Site Not Available

  • Investigational Site

    Newport Beach, California 92663
    United States

    Site Not Available

  • Investigational Site

    Sacramento, California 95819
    United States

    Site Not Available

  • Investigational Site

    San Francisco, California 94143
    United States

    Site Not Available

  • Investigational Site

    Aurora, Colorado 80012
    United States

    Site Not Available

  • Investigational Site

    Bridgeport, Connecticut 06610
    United States

    Site Not Available

  • Investigational Site

    Washington, District of Columbia 20010
    United States

    Site Not Available

  • Investigational Site

    Washington DC, District of Columbia 20010
    United States

    Site Not Available

  • Investigational Site

    Daytona Beach, Florida 32117
    United States

    Site Not Available

  • Investigational Site

    Lakeland, Florida 33805
    United States

    Site Not Available

  • Investigational Site

    Takoma Park, Maryland 20912
    United States

    Site Not Available

  • Investigational Site

    Towson, Maryland 21204
    United States

    Site Not Available

  • Investigational Site

    Lincoln, Nebraska 68506
    United States

    Site Not Available

  • Investigational Site

    Rochester, New York 14642
    United States

    Site Not Available

  • Investigational Site

    Utica, New York 13501
    United States

    Site Not Available

  • Investigational Site

    Cleveland, Ohio 44106
    United States

    Site Not Available

  • Investigational Site

    Columbus, Ohio 43210
    United States

    Site Not Available

  • Investigational Site

    Ephrata, Pennsylvania 17522
    United States

    Site Not Available

  • Investigational Site

    Lancaster, Pennsylvania 17602
    United States

    Site Not Available

  • Investigational Site

    Sayre, Pennsylvania 18840
    United States

    Site Not Available

  • Investigational Site

    Wynnewood, Pennsylvania 19096
    United States

    Site Not Available

  • Investigational Site

    Warwick, Rhode Island 02886
    United States

    Site Not Available

  • Investigational Site

    Charleston, South Carolina 29425
    United States

    Site Not Available

  • Investigational Site

    Germantown, Tennessee 38138
    United States

    Site Not Available

  • Investigational Site

    Houston, Texas 77030
    United States

    Site Not Available

  • Investigational Site

    San Antonio, Texas 78229
    United States

    Site Not Available

  • Investigational Site

    Murray, Utah 84107
    United States

    Site Not Available

  • Investigational Site

    Seattle, Washington 98122
    United States

    Site Not Available

  • Investigational Site

    Madison, Wisconsin 53713
    United States

    Site Not Available

  • Investigational Site

    Wausau, Wisconsin 54401
    United States

    Site Not Available

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