Summary of bioequivalence study for PERINDOPRES DUO, 4 mg perindopril tert-butylamine / 1.25 mg indapamide tablets; 8 mg perindopril tert-butylamine / 2.5 mg indapamide tablets

20 January 2023

Purpose. To prove the bioequivalence (BE) of the test investigational medicinal product (IMP) PERINDOPRES^® DUO, 8 mg perindopril tert-butylamine / 2.5 mg indapamide tablets, manufactured by PrJSC “Pharmaceutical Firm “Darnitsa” to the reference IMP NOLITERAX^® 10 mg/2.5 mg, film-coated tablets containing 10 mg perindopril arginine / 2.5 mg indapamide, manufactured by Servier (Ireland) Industries Ltd in a randomized, open-label, single-dose, two-sequence, two-period, crossover, comparative, oral bioequivalence study in 42 healthy volunteers under fasting conditions.

Objects and methods of the study. In each period, healthy male and female volunteers took under fasting conditions a single oral dose of test or reference IMPs, i.e., either 8 mg perindopril tert-butylamine or 10 mg perindopril arginine and 2.5 mg indapamide (i.e., 13,466 mg of perindopril and 5 mg indapamide throughout the study). Data of forty-one (41) healthy volunteers fully completed the study according to the protocol and taken IMP in both periods were included in pharmacokinetic and statistical analysis.

Results. Pharmacokinetic results demonstrate that perindopril geometric least squares mean (LSM) ratios and corresponding 90% confidence intervals (CIs) for maximum plasma concentration (Cmax) and area under the plasma concentration curve from administration to last observed concentration at time (t) (AUC0-t) were 88.48% (81.21 to 96.41%) and 96.73% (93.74 to 99.83%), respectively. For indapamide, geometric LSM ratios and corresponding 90% CIs for Cmax and AUC0-t were 112.75% (106.91 to 118.92%) and 98.02% (93.23 to 103.06%), respectively.

The criteria used to assess bioequivalence between the test and reference IMPs were all fulfilled since the Test to Reference ratio of geometric LSM and corresponding 90% CIs for Cmax and AUC0-t were all within the acceptance range of 80.00 to 125.00%.

During the study, no clinically significant and drug-related changes were detected in healthy volunteers based on the assessment of vital signs, physical examination, electrocardiography and laboratory tests.

Conclusions. The bioequivalence of the test IMP (PERINDOPRES^® DUO, 8 mg perindopril tert-butylamine / 2.5 mg indapamide tablets) to the reference IMP (NOLITERAX^® 10 mg/2.5 mg, film-coated tablets containing 10 mg perindopril arginine / 2.5 mg indapamide) was demonstrated in this study. Both IMPs were characterized to have good tolerability after single (within each period) oral administration under fasting conditions.

The Sponsor of the study, PrJSC “Pharmaceutical Firm “Darnitsa”, expresses its gratitude to the employees of contract research organization (CRO) International Pharmaceutical Research Center (IPRC) in Amman, Jordan, for conducting this study and processing its results.

For more details about the study, please see Annex 30 published on the official site of the State Expert Center of the Ministry of Health of Ukraine: https://www.dec.gov.ua/materials/perindopres-duo/?role=ua.