A dose-response study of clentiazem, a chloro-derivative of diltiazem, in patients with stable angina. CAMCAT Study Group.
OBJECTIVE
The efficacy and safety of clentiazem were assessed in 199 patients with stable angina in a dose-ranging, placebo-controlled, 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 titration. 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 > or = 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 treatment-related 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.
Waters
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Department of Medicine, Montreal Heart Institute, Quebec, Canada.
Garceau
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D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D001247:Asthenia / Q000139:chemically induced; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004110:Diltiazem / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D002121:Calcium Channel Blockers; C056595:clentiazem; D004110:Diltiazem