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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dexa Medica Group
ClinicalTrials.gov Identifier:
NCT01682577
First received: September 3, 2012
Last updated: September 6, 2012
Last verified: September 2012
  Purpose

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).


Condition Intervention
Healthy
Drug: Perindopril 4 mg tablets of PT Dexa Medica
Drug: Perindopril 4 mg tablets of Servier

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Dexa Medica Group:

Primary Outcome Measures:
  • Area under concentration-time curve (AUC)of perindopril parent compound [ Time Frame: 192 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 192 hours ] [ Designated as safety issue: No ]
    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:
  • Peak plasma concentration (Cmax)of perindopril parent compound [ Time Frame: 192 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 192 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 192 hours ] [ Designated as safety issue: No ]
  • Time to achieve the peak plasma concentration (tmax)of perindoprilat [ Time Frame: 192 hours ] [ Designated as safety issue: No ]
  • Elimination half-life (t1/2)of perindopril parent compound [ Time Frame: 192 hours ] [ Designated as safety issue: No ]
  • Elimination half-life (t1/2)of perindoprilat [ Time Frame: 192 hours ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: September 2008
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: Perindopril 4 mg tablets of PT Dexa Medica
Test product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.
Other Names:
  • Test Product: Perindopril 4 mg tablets of PT Dexa Medica.
  • Each tablet contains perindopril tert-butylamine salt 4 mg
Active Comparator: 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.

Drug: Perindopril 4 mg tablets of Servier
Reference product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.
Other Names:
  • Reference product: Prexum® 4 mg, produced by Servier.
  • Each tablet contains Perindopril tert-butylamine salt 4 mg.

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).

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01682577

Locations
Indonesia
PT Equilab International
Jakarta, Indonesia, 12430
Sponsors and Collaborators
Dexa Medica Group
Investigators
Principal Investigator: Danang A Yunaidi, MD PT Equilab International
  More Information

Publications:
Responsible Party: Dexa Medica Group
ClinicalTrials.gov Identifier: NCT01682577     History of Changes
Other Study ID Numbers: PR.122/EQL/2008
Study First Received: September 3, 2012
Last Updated: September 6, 2012
Health Authority: Indonesia: National Agency of Drug and Food Control

Keywords provided by Dexa Medica Group:
Perindopril
Perindoprilat
Bioequivalence
Pharmacokinetic
Angiotensin-converting enzyme inhibitor

Additional relevant MeSH terms:
Angiotensin-Converting Enzyme Inhibitors
Perindopril
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014