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

Not Applicable

Completed

• Conditions: Healthy
• Interventions: Drug: Perindopril 4 mg tablets of PT Dexa Medica; Drug: Perindopril 4 mg tablets of Servier

• Registration Number: NCT01682577
• Lead Sponsor: Dexa Medica Group

Brief Summary

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

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).

Study Timeline

• Study Start: 2008-09
• Primary Completion: 2008-11
• Study Completion: 2008-12
• Status Verified: 2012-09
• Study First Submitted: 2012-09-03
• Study First Submitted QC: 2012-09-06
• Last Update Submitted: 2012-09-06
• Study First Posted: 2012-09-11
• Last Update Posted: 2012-09-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Perindopril 4 mg tablets of PT Dexa Medica	Perindopril 4 mg tablets of PT Dexa Medica	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.
Perindopril 4 mg tablets of Servier	Perindopril 4 mg tablets of Servier	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.

Primary Outcome Measures

Name	Time	Method
Area under concentration-time curve (AUC)of perindopril parent compound	192 hours	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.
Area under concentration-time curve (AUC)of perindoprilat	192 hours	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.

Secondary Outcome Measures

Name	Time	Method
Elimination half-life (t1/2)of perindopril parent compound	192 hours
Peak plasma concentration (Cmax)of perindopril parent compound	192 hours	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.
Peak plasma concentration (Cmax)of perindoprilat	192 hours	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.
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 perindoprilat	192 hours

Trial Locations

Locations (1)

PT Equilab International; 🇮🇩 Jakarta, Indonesia