Gilead Sciences has announced results from HARMONY, a randomized, double-blind, placebo-controlled phase 2 study evaluating the effect of Ranolazine and low-dose Dronedarone, each given alone and in combination, on atrial fibrillation burden in patients with paroxysmal atrial fibrillation.
In HARMONY, the combination of Ranolazine and low-dose Dronedarone provided greater reductions in atrial fibrillation burden from baseline than either therapy used alone.
Ranolazine is approved in the United States under the tradename Ranexa for the treatment of chronic angina at marketed doses of 500 mg and 1,000 mg twice daily. Ranexa with or without Dronedarone is not approved for the treatment of atrial fibrillation.
In the study, patients in the Ranolazine 750 mg / Dronedarone 150 mg ( RD150 ) and Ranolazine 750 mg / Dronedarone 225 mg ( RD225 ) arms experienced respective reductions of 45% and 59% in atrial fibrillation burden from baseline over 12 weeks ( p=0.072 and p=0.008, respectively, versus placebo ).
Among patients receiving RD225, 45% has achieved atrial fibrillation burden reductions from baseline of greater than or equal to 70% over 12 weeks. Neither Ranolazine 750 mg ( p=0.49 ) nor Dronedarone 225 mg ( p=0.78 ) alone caused statistically significant reductions in atrial fibrillation burden from baseline compared to placebo. These results are consistent with pre-clinical findings of a synergistic effect when these therapies are used in combination.
In HARMONY, 134 patients were randomized to one of five treatment arms: placebo ( n=26 ); Ranolazine 750 mg tablet twice daily ( n=26 ); Dronedarone 225 mg capsule twice daily ( n=26 ); RD150 twice daily ( n=26 ); or RD225 twice daily ( n=27 ).
There was no clinically significant difference between active treatment groups in the overall incidence of adverse events or adverse events leading to discontinuations. Among the most frequent adverse events leading to discontinuation within each treatment group were: atrial fibrillation ( placebo, two patients ), vertigo and dizziness ( Ranolazine 750 mg, two patients each ), dyspnea and pruritus ( Dronedarone 225 mg, two patients each ), hypotension ( RD225, two patients ) and no adverse events leading to discontinuation were reported for more than one patient in the RD150 group ( e.g., dizziness and constipation ).
The primary endpoint was change in atrial fibrillation burden over 12 weeks. Atrial fibrillation burden was defined as the total time a patient was in atrial tachycardia / atrial fibrillation expressed as percentage of total recording time continuously from 0 to 12 weeks. ( Xagena )
Source: Gilead, 2014