|Design||Double-blind, 4-period crossover, placebo-controlled, n = 191 randomized||Double-blind, parallel group, placebo-controlled, n = 823 randomized||Double-blind, 3-period crossover, placebo-controlled, n = 158 randomized||Double blind, parallel group, placebo-controlled, n = 565 randomized|
|Treatments and duration||Ranolazine ER 500, 1,000, or 1,500 mg or placebo twice a day as monotherapy for 1 week each||Ranolazine ER at 750 or 1,000 mg or placebo twice a day for 12 weeks. Background treatment with diltiazem 180 mg QD, atenolol 50 mg QD, or amlodipine 5 mg QD||Ranolazine IR 400 mg TID, atenolol 100 mg QD and placebo for 1 week each||Ranolazine ER 1,000 mg twice a day or placebo for 6 weeks, preceded by ranolazine ER 500 mg twice a day or placebo for 1 week. Background therapy with amlodipine 10 mg QD throughout dosing and at least 4 weeks before.|
|Primary efficacy measure||Exercise duration on treadmill at trough ranolazine concentration||Exercise duration on treadmill at trough ranolazine concentration||Time to onset of angina during treadmill or bicycle exercise testing at peak ranolazine concentration||Average weekly frequency of angina attacks|
|Secondary efficacy measures||Time to angina onset and time to 1-mm ST-segment depression at trough and peak; exercise duration at peak||Time to angina onset; time to 1-mm ST-segment depression at trough and peak; frequency of angina attacks; exercise duration at peak; frequency of NTG use||Time to 1-mm ST-segment depression and exercise duration at peak ranolazine concentration||Average weekly NTG consumption; scores in 5 dimensions of SAQ (angina frequency, physical limitations, anginal stability, disease perception, and treatment satisfaction)|
|Summary of efficacy results||Exercise duration at trough increased in dose-dependent fashion relative to placebo (23.8 s, 33.7 s, 45.9 s for 500 mg, 1,000 mg, 1,500 mg dose, respectively, p < 0.005).||Exercise duration at trough increased by 23.7 s (750 mg dose) and 24.0 s (1,000 mg dose) relative to placebo (p = 0.03 and p = 0.029, respectively).||Time to onset of angina inreased by 51.0 s relative to placebo (p < 0.001) on ranolazine, 39.5 s on atenolol (p < 0.001).||Angina frequency reduced by 0.43 episodes per week relative to placebo (p = 0.028).|
|Significant, dose-related increases in exercise duration at peak and in time to angina onset and time to 1-mm ST-segment depression at peak and trough.||Significant increases in exercise duration, time to angina onset and time to 1-mm ST-segment depression at peak, and in time to angina onset at trough. Significant reduction in average weekly angina frequency and nitroglycerin consumption.||Exercise duration and time to 1-mm ST-segment depression significantly increased relative to placebo.||NTG consumption significantly reduced. SAQ angina frequency assessment significantly improved. Other SAQ dimensions not significantly changed.|
CARISA = Combination Assessment of Ranolazine in Stable Angina; ER = extended release; ERICA = Efficacy of Ranolazine In Chronic Angina trial; MARISA = Monotherapy Assessment of Ranolazine in Stable Angina; NTG = nitroglycerin; QD = once per day; RAN080 = Ranolazine clinical study #080; SAQ = Seattle Angina Questionnaire; TID = three times per day.