Bioequivalence Study of Two Formulations of Perindopril 4 mg Tablet Under Fasting Condition

Study Overview
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Brief Summary
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The objective of this study was to find out whether the bioavailability of PT Dexa Medica's formulation of 4 mg perindopril tert-butylamine tablets was equivalent to that of the innovator's product (Prexum® 4 mg, Servier).

Detailed Description
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The participating subjects were required to have an overnight fast and in the next morning were given orally one tablet of the test drug (Perindopril 4 mg tablets of PT Dexa Medica) or one tablet of the reference drug (Prexum® 4 mg, Servier). Blood samples were drawn immediately before taking the drug (control), and at 20, 40 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 192 hours after drug administration. Three weeks after the first drug administration (washout period), the procedure was repeated using the alternate drug. The pharmacokinetic parameters, including AUCt, AUCinf, Cmax, t max, and t1/2, were determined based on the concentrations of the perindopril parent compound and the metabolite perindoprilat, using high-performance liquid chromatography method with tandem mass spectrometry detector (LC-MS/MS).

Official Title
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Bioequivalence Study of 4 mg Perindopril Tablets Produced by PT Dexa Medica in Comparison With the Reference Tablets (Prexum® 4 mg, Servier)Under Fasting Condition

Conditions
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Healthy

Intervention / Treatment
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* Drug: Perindopril 4 mg tablets of PT Dexa Medica
* Drug: Perindopril 4 mg tablets of Servier


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects Aged 18-55 years inclusive A body mass index in the range of 18-25 kg/m2 Able to participate, communicate well with the investigators and willing to give informed consent Non-smokers Vital signs (after 10 minutes resting) are within the following ranges: systolic blood pressure 100-125 mmHg diastolic blood pressure 60-80 mmHg pulse rate 60-90 bpm Exclusion Criteria: Pregnant or lactating women Known hypersensitivity or contraindication to perindopril Intake of any prescription drug within 14 days of this study's first dosing day Intake of any non-prescription drug, food supplement, or herbal medicine within 7 days of this study's first dosing day History or presence of any liver dysfunction (ALT, alkaline phosphatase, total bilirubin ≥ 1.5 ULN) History of any bleeding or coagulation disorders Clinically significant ECG abnormalities Clinically significant haematology abnormalities Renal insufficiency (plasma creatinine concentration ≥ 1.4 mg/dL) Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drug A donation or loss of 500 mL (or more) of blood within 3 months before this study's first dosing day A positive hepatitis B surface antigen (HBsAg), anti-HCV, and anti-HIV History of drug or alcohol abuse within 12 months prior to screening of this study Participation in a previous study within 3 months of this study's first dosing day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perindopril 4 mg tablets of PT Dexa Medica<br>Group I (Test product): each tablet contains perindopril tert-butylamine salt 4 mg. A single dose of perindopril tablet of PT Dexa Medica was given to each of study subjects. | Drug: Perindopril 4 mg tablets of PT Dexa Medica<br>* Test product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.<br>* Other names: Each tablet contains perindopril tert-butylamine salt 4 mg;|
| Active Comparator: Perindopril 4 mg tablets of Servier<br>Group II (Reference product) : each tablet contains perindopril tert-butylamine salt 4 mg. A single dose of perindopril (Prexum) tablets of Servier was given to each of study subjects. | Drug: Perindopril 4 mg tablets of Servier<br>* Reference product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.<br>* Other names: Each tablet contains Perindopril tert-butylamine salt 4 mg.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under concentration-time curve (AUC)of perindopril parent compound | Relative bioavailability (primarily measured by AUCt and AUCinf) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The AUC was measured based on the plasma concentration of perindopril parent compound. | 192 hours | 
| Area under concentration-time curve (AUC)of perindoprilat | Relative bioavailability (primarily measured by AUCt and AUCinf) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The AUC was measured based on the plasma concentration of the active metabolite, perindoprilat. | 192 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax)of perindopril parent compound | Relative bioavailability (secondarily measured by Cmax) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The Cmax was measured based on the plasma concentration of perindopril parent compound. | 192 hours | 
| Peak plasma concentration (Cmax)of perindoprilat | Relative bioavailability (secondarily measured by Cmax) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The Cmax was measured based on the plasma concentration of the active metabolite, perindoprilat. | 192 hours | 
| Time to achieve the peak plasma concentration (tmax)of perindopril parent compound |  | 192 hours | 
| Time to achieve the peak plasma concentration (tmax)of perindoprilat |  | 192 hours | 
| Elimination half-life (t1/2)of perindopril parent compound |  | 192 hours | 
| Elimination half-life (t1/2)of perindoprilat |  | 192 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perindopril, Perindoprilat, Bioequivalence, Pharmacokinetic, Angiotensin-converting enzyme inhibitor