A clinical trial designed to compare how effective ranolazine or drondarone, given either alone or in combination, are in treating sudden, but intermittent, rapid heart beat (atrial fibfillation)

• Register: EUCTR
• Last refreshed on: 24 March 2014
• Main ID: EUCTR2011-001134-42-NL
• Date of registration: 28/02/2012
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc
• Public title: A clinical trial designed to compare how effective ranolazine or drondarone, given either alone or in combination, are in treating sudden, but intermittent, rapid heart beat (atrial fibfillation)
• Scientific title: A phase 2, proof of concept, randomised, 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 - HARMONY
• Date of first enrolment: 22/05/2012
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001134-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 5

Countries of recruitment

Germany, Israel, Italy, Netherlands, Poland, United Kingdom, United States

Contacts

• Name: International Regulatory Affairs
• Affiliation: Gilead Sciences International Ltd

• Name: International Regulatory Affairs
• Affiliation: Gilead Sciences International Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males and females aged 18 years and older
2. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
3. History of PAF documented within the prior 12 months
— Patients with PAF undergoing cardioversion greater than 4 weeks prior to Screening are eligible
4. Implanted (at least 3 months prior to Screening) dual chamber programmable pacemakers with AF detection capabilities
5. AFB = 1% and = 70% between the last clinic evaluation and Screening (minimum of 1 month observation period) and AFB = 2% and = 70% during the 4-week Run-in period
6. 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
1. Persistent AF or Permanent AF
2. History of atrial flutter or atrial tachycardia without successful
ablation
3. Other acutely reversible causes of AF, including but not limited to:
hyperthyroidism, pericarditis, myocarditis, or pulmonary embolism
4. 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.
5. Recent history of left ventricular ejection fraction (LVEF) < 40%
6. 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
7. Clinically significant valvular disease in the opinion of the Investigator
8. Stroke within 3 months prior to Screening
9. History of serious ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation) within 4 weeks prior to Screening
10. Family history of long QT syndrome
11. 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
12. Prior heart transplant
13. Cardiac ablation within 4 months prior to Screening, or planned
ablation during the course of the study
14. Need for concomitant treatment during the trial, with drugs or
products that are strong inhibitors of CYP3A, or inducers of CYP3A
15. Use of grapefruit juice or Seville orange juice during the study
16. Use of Class I and Class III antiarrhythmic drugs other than
amiodarone
17. Use of amiodarone within 3 months prior to Screening
18. Use of drugs that prolong the QT interval
19. Previous use of ranolazine or dronedarone within 2 months prior to screening
20. Prior use of ranolazine or dronedarone which was discontinued for safety or tolerability
21 Use of dabigatran during the study
22. Use of digitalis preparations (eg, digoxin) during the study
23. Use of a greater than 1000 mg total daily dose of metformin
24. 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
25.Moderate and severe hepatic impairment (ie, Child-Pugh Class B and C), abnormal liver function test defined as ALT, AST, or bilirubin > 2 x ULN at Screening
26. Severe renal impairment defined as creatinine clearance = 30
mL/min at Screening
27. Females who are pregnant or are breastfeeding


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Paroxysmal Atrial Fibrillation
MedDRA version: 14.1 Level: LLT Classification code 10034039 Term: Paroxysmal atrial fibrillation System Organ Class: 100000004849

Intervention(s)

Trade Name: Ranexa
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: RANOLAZINE
CAS Number: 95635-55-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 750-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: dronedarone
Pharmaceutical Form: Capsule
INN or Proposed INN: DRONEDARONE
CAS Number: 141626-36-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 225-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: dronedarone
Pharmaceutical Form: Capsule
INN or Proposed INN: DRONEDARONE
CAS Number: 141626-36-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the effect of ranolazine and of low dose dronedarone when given alone and in combination at different dose levels on AFB over 12 weeks of treatment

AFB is defined as the total time a subject is in atrial tachycardia/atrial fibrillation (AT/AF) expressed as a percentage of total recording time.

Secondary Objective: To evaluate the effect of ranolazine and of dronedarone when given alone and in combination at different dose levels on:
— Atrial fibrillation burden for each visit period
— Number of atrial fibrillation episodes, duration of atrial fibrillation episodes, and ventricular rate during atrial fibrillation episodes
— Ventricular rate over 12-weeks of treatment and for each visit period
— Percentage of ventricular pacing
— Percentage of atrial pacing
— Incidence of persistent atrial fibrillation
— Incidence of electrical cardioversion
— Incidence of symptomatic episodes

To determine the percentage of subjects who have = 30% (= 50%) reduction from baseline in AFB

To determine the percentage of subjects who have total duration of AF episodes = 5.5 hours per day at any point during the treatment period

Primary end point(s): Change from baseline in atrial fibrillation burden (both percent change and absolute change).

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 4, 8 and 12 weeks

Secondary end point(s): 1. Change from baseline in atrial fibrillation burden for each visit period 2. Change from baseline in number of AF episodes, duration of AF episodes, and ventricular rate for AF episodes
3. Change from baseline in ventricular rate for each visit period
4. Percent ventricular pacing for each visit period
5. Percent atrial pacing
6. Incidence of persistent atrial fibrillation
7. Incidence of electrical cardioversion
8. Incidence of symptomatic episodes

Secondary ID(s)

2011-001134-42-DE

GS-US-291-0102

Source(s) of Monetary Support

Gilead Sciences Inc