Regulatory Decision Summary for APO-Perindopril Arginine

Perindopril, the active ingredient in Coversyl and Arcosyl is rapidly absorbed following oral administration and is subsequently converted into perindoprilat, its active metabolite. Irrespective of whether the arginine or erbumine salt form of perindopril was administered orally, only perindopril and its metabolites were measured in the systemic circulation during pre-clinical and clinical trials. Accordingly, in all clinical pharmacology and pharmacokinetic studies reviewed for the approval of either salt of perindopril, pharmacokinetic information was provided for perindopril, not for perindopril erbumine or perindopril arginine.

The bioavailability of perindopril from administration of a 10 mg dose of the APO-Perindopril Arginine (perindopril arginine) is comparable to the bioavailability of perindopril from administration of an 8 mg dose of the Coversyl (perindopril erbumine) under fasting conditions. The study met the applicable comparative bioavailability standards for perindopril on log transformed parameters calculated from measured data. In addition, the measured drug content of the lots of the test and reference products used in the study (percent of label claim) were within 5% of each other.

A waiver was requested from conducting a comparative bioavailability study with the 2.5 mg and 5 mg strengths on the basis of their proportionality to the 10 mg strength that was administered in bioavailability study. The waiver was granted based on the proportionality of the strengths and comparative dissolution profiles which met the requirements of the Bioequivalence of Proportional Formulations - Solid Oral Dosage Forms (1996) policy.

No new clinical efficacy and safety studies were filed for this submission. The demonstration of comparable bioavailability of perindopril from APO-Perindopril Arginine (perindopril arginine) and Coversyl (perindopril erbumine) is considered to be sufficient as evidence of safety and efficacy.