Clinical trial NCT01682577: Bioequivalence Study of Two Formulations of Perindopril 4 mg Tablet Under Fasting Condition
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Perindopril
Perindoprilat
Bioequivalence
Pharmacokinetic
Angiotensin-converting enzyme inhibitor
Lead sponsor: Dexa Medica Group
Sponsor class: INDUSTRY
First posted: 2012-09-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Area under concentration-time curve (AUC)of perindopril parent compound
timeFrame: 192 hours
measure: Area under concentration-time curve (AUC)of perindoprilat
timeFrame: 192 hours
Secondary outcomes:
measure: Peak plasma concentration (Cmax)of perindopril parent compound
timeFrame: 192 hours
measure: Peak plasma concentration (Cmax)of perindoprilat
timeFrame: 192 hours
measure: Time to achieve the peak plasma concentration (tmax)of perindopril parent compound
timeFrame: 192 hours
measure: Time to achieve the peak plasma concentration (tmax)of perindoprilat
timeFrame: 192 hours
measure: Elimination half-life (t1/2)of perindopril parent compound
timeFrame: 192 hours
measure: Elimination half-life (t1/2)of perindoprilat
timeFrame: 192 hours
Other outcomes:
Locations:
city: Jakarta
country: Indonesia
facility: PT Equilab International
Study officials:
affiliation: PT Equilab International
name: Danang A Yunaidi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1046/j.0306-5251.2001.01410.x.
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. doi: 10.1097/00005344-199209000-00024.
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. doi: 10.1111/j.1365-2125.1992.tb04006.x.