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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01682577
• Other study ID #: PR.122/EQL/2008
• Status: Completed
• Phase: N/A
• First received: September 3, 2012
• Last updated: September 6, 2012
• Start date: September 2008
• Est. completion date: December 2008

Study information

• Verified date: September 2012
• Source: Dexa Medica Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Indonesia: National Agency of Drug and Food Control
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

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.
• 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.

Locations

Country	Name	City	State
Indonesia	PT Equilab International	Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Dexa Medica Group

Country where clinical trial is conducted

Indonesia, 

References & Publications (3)

Bellissant E, Giudicelli JF. Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients. Br J Clin Pharmacol. 2001 Jul;52(1):25-33. — View Citation

Louis WJ, Workman BS, Conway EL, Worland P, Rowley K, Drummer O, McNeil JJ, Harris G, Jarrott B. Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects. J Cardiovasc Pharmacol. 1992 Sep;20(3):505-11. — View Citation

Sennesael J, Ali A, Sweny P, Vandenburg M, Slovic D, Dratwa M, Resplandy G, Genissel P, Desche P. The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure. Br J Clin Pharmacol. 1992 Jan;33(1):93-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Time to achieve the peak plasma concentration (tmax)of perindopril parent compound		192 hours	No
Secondary	Time to achieve the peak plasma concentration (tmax)of perindoprilat		192 hours	No
Secondary	Elimination half-life (t1/2)of perindopril parent compound		192 hours	No
Secondary	Elimination half-life (t1/2)of perindoprilat		192 hours	No