A dose-response study of clentiazem, a chloro-derivative of diltiazem, in patients with stable angina

Abstract

Objectives. The efficacy and safety of clentiazem were assessed in 199 patients with stable angina in a dose-ranging, placebocontrolled, double-blind, parallel design study.Background. To date, this is the first large efficacy and safety study of clentiazem in patients with stable angina.Methods. After washout and a 1-week placebo run-in period, patients received 20,40,80 or 120 mg/day of clentiazem tablets or placebo as a twice-daily dosage for 1 week of treatment after 1 week of dose titratlon. A symptom-limited exercise tolerance test was performed 4 and 12 h after dosing at the end of treatment and results were compared with baseline measurements.Results. At 4 h after dosing, improvement of exercise duration from baseline value was significantly greater with clentiazem at doses of 40 mg/day (63 ± 11 s), 80 mg/day (99 ± 10 s) and 120 mg/day (70 ± 11 s) than with placebo (34 ± 10 s). Moreover, clentiazem (80 and 120 mg/day) increased the time to onset of angina and to ≥1 mm of ST segment depression significantly more than did placebo. At submaximal exercise, clentiazem (40, 80 and 120 mg/day) decreased rate-pressure product, mainly as a result of a decrease in heart rate. At 12 h after dosing, improvement of exercise duration from baseline was significantly greater with clentiazem in doses of 80 mg/day (77 ± 9 s) and 120 mg/day (70 ± 10 s) than with placebo (42 ± 9 s). The incidence of treatmentrelated adverse events with placebo (27%) and clentiazem (29%) was similar. The most frequently reported treatment-related adverse events with clentiazem were asthenia, headache (both 7.9%), first-degree atrioventricular block and dizziness (both 4.4%).Conclusions. The results of this short-term study suggest that clentiazem given twice daily in doses of 80 or 120 mg/day is safe and effective monotherapy in the treatment of stable angina.