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(Circulation. 2003;107:e9052.)
© 2003 American Heart Association, Inc.

Proceedings of the 99th Meeting of the Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee

May 29th and 30th, 2003

Jeffrey Borer, MD; Paul Armstrong, MD

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The committee reviewed two new drug applications (NDAs) that previously had received "approvable" actions. Initial submissions had shown that these two compounds might have a prolonging effect on the QT interval. Therefore, sponsors were asked to undertake additional studies that incorporated an evaluation of QTc (QT interval corrected) prolongation at plasma concentrations relevant for monotherapy at the proposed labeled doses, as well as at concentrations expected to be achieved as a result of pharmacokinetic interaction with drugs that plausibly might be administered concomitantly.

The first of the drugs, alfuzosin, is an ₁-adrenergic receptor antagonist known to improve urinary flow rate in patients with symptoms of benign prostatic hypertrophy. The sponsor presented data from a crossover study of 48 healthy white men between the ages of 18 and 50 years given single doses of alfuzosin targeting therapeutic (10 mg) and supratherapeutic (40 mg) blood levels. Maximum changes in QT interval and QTc interval were measured and compared with changes in individuals who took placebo or moxifloxacin (400 mg), a drug that is known to prolong QT interval. Approximately 10 mg alfuzosin caused a modest dose-related increase in QTc from baseline that was less than the increase caused by moxifloxacin relative to placebo.

The second drug, vardenafil, is a potent phosphodiesterase 5 inhibitor. It was studied in 59 healthy adult men between the ages of 45 and 60 years, using sequential 12-lead ECGs at specified intervals. Studies were conducted with doses targeting therapeutic (10 mg) and supratherapeutic (80 mg) blood levels. As . . . [Full Text of this Article]