Very important data for comparison (current data and future CLTX results). I am not very impressed with CVTX results (to high placebo effect???), and start to think that I was more than enough (than should be) critical in respond:
Message 16229790
Miljenko
CARISA results:
"Study Detail
The CARISA (Combination Assessment of Ranolazine In Stable Angina) study was a Phase III multi-national, randomized, double-blind, placebo-controlled, parallel group trial of the safety and efficacy of ranolazine. The clinical trial randomized 823 patients to assess the anti-anginal effects of 12 weeks of treatment with ranolazine in chronic angina patients also receiving a background anti-anginal medication. Patients received one of three background therapies (atenolol 50 mg, diltiazem CD 180 mg, or amlodipine 5 mg) and were randomized to twice daily doses of ranolazine 750 mg, ranolazine 1000 mg, or placebo. Exercise testing was performed at trough plasma concentrations (12 hours after dosing) after 2, 6, and 12 weeks and at peak plasma concentrations (4 hours after dosing) after 2 and 12 weeks. The prospectively defined primary efficacy endpoint was symptom-limited exercise duration at trough for all ranolazine patients compared to placebo at 12 weeks. The CARISA primary efficacy endpoint of symptom-limited exercise duration at trough has historically been the primary endpoint that the FDA reviews when considering anti-anginal therapies.
Study Results
In both ranolazine dose groups combined, symptom-limited exercise duration at trough plasma concentrations, the primary endpoint of the trial, increased on ranolazine by an average of 116 seconds, compared to an average increase of 92 seconds on placebo (p=0.012). The average increases in symptom-limited exercise duration at trough plasma concentrations on each ranolazine dose, considered independently, were 115 seconds on 750 mg and 116 seconds on 1000 mg, compared to 92 seconds on placebo (p<=0.03). The increases in exercise times on ranolazine were not significantly different among the three background therapies; insignificantly greater increases were seen over diltiazem and amlodipine than over atenolol.
Statistically significant effects of ranolazine were also observed in other secondary efficacy endpoints. Ranolazine at doses of 750 mg and 1000 mg reduced the frequency of angina by an average of 1.3 and 1.7 attacks per week, respectively, compared to an average decrease of 0.6 attacks per week on placebo (p<=0.01 for each dose versus placebo). Compared to placebo, ranolazine at doses of 750 mg and 1000 mg increased the average time to electrocardiographic evidence of ischemia; these increases approached statistical significance at trough (20 and 21 seconds, respectively; p<=0.1) and achieved statistical significance at peak (41 and 35 seconds, respectively; p<0.005). In addition, compared to placebo, ranolazine at both doses statistically significantly increased the average time to onset of angina at both peak (38 seconds on each dose; p<=0.003) and trough (30 and 26 seconds, respectively; p<=0.05).
Compared to placebo, systolic blood pressure after 12 weeks of treatment decreased, on average, by 2 mm Hg on 750 mg (p=NS) and by 3 mm Hg on 1000 mg (p=0.02). Average heart rate at the same time point was 1 bpm less on either dose than on placebo, differences which were not statistically significant.
Side effects more common during ranolazine treatment than during placebo treatment included constipation, dizziness, nausea, and asthenia. The adverse event rate was 26% for placebo, 31% for ranolazine 750 mg, and 33% for ranolazine 1000 mg. Small (<10 milliseconds, similar to MARISA) but statistically significant (p<=0.002) increases in QTc were observed compared to placebo. Serious adverse events were observed in 6%, 7%, and 7% of patients on placebo, ranolazine 750 mg, and ranolazine 1000 mg respectively." |
