Bioequivalence Study of Two Formulations of 10 mg Lisinopril Tablet Under Fasting Condition

Condition(s) targeted: Healthy

Intervention: Lisinopril 10 mg tablets of PT Dexa Medica (Drug); Lisinopril 10 mg tablets of PT Boehringer Ingelheim Indonesia (Drug)

Phase: N/A

Status: Completed

Sponsored by: Dexa Medica Group

The present study was conducted to find out whether the bioavailability of 10 mg lisinopril tablets produced by PT Dexa Medica was equivalent to the tablets produced by the innovator (Zestril® 10 mg, PT Boehringer Ingelheim Indonesia, Indonesia, under license from Astra Zeneca UK Ltd.)

Official title: Bioequivalence Study of 10 mg Lisinopril Tablets (Lisinopril 10 mg) Produced by PT Dexa Medica in Comparison With The Innovator Tablets (Zestril® 10 mg, PT Boehringer Ingelheim Indonesia, Indonesia, Under License From Astra Zeneca UK Ltd.)

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

Primary outcome:

Area under the plasma concentration-time curve from time zero to the last observed quantifiable concentration (AUCt) of lisinopril

Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of lisinopril

Secondary outcome:

The peak plasma concentration (Cmax) of lisinopril

Time needed to achieve the peak plasma concentration (t max) of lisinopril

The elimination half-life (t1/2) of lisinopril

Detailed description: This was a randomized, single-blind, two-period, two-sequence, cross-over study under fasting condition. The participating subjects were required to have an overnight fast and in the next morning were given orally one tablet of the test drug (Lisinopril 10 mg, produced by PT Dexa Medica) or one tablet of the reference drug (Zestril® 10 mg, PT Boehringer Ingelheim Indonesia, Indonesia, under license from Astra Zeneca UK Ltd.). Blood samples were drawn immediately before taking the drug (control), and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, and 48 hours after drug administration. Seven days 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 from plasma concentrations of lisinopril, using liquid chromatography with tandem mass spectrometry detection (LC-MS/MS) method.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Healthy male and female subjects.

- Aged 18 - 55 years inclusive.

- Non-smokers or moderate smokers (less than 10 cigarettes per day).

- Able to participate, communicate well with the investigators and willing to provide

written informed consent to participate in the study.

- Body mass index within 18 to 25 kg/m2.

- Vital signs (after 10 minutes rest) were within the following ranges:

- systolic blood pressure 110 - 120 mmHg

- diastolic blood pressure 70 - 80 mmHg

- pulse rate 60 - 90 bpm

Exclusion Criteria:

- Personal/family history of allergy or hypersensitivity or contraindication to

lisinopril or allied drugs.

- Pregnant or lactating women.

- Any major illness or clinically significant ongoing chronic medical illness in the

past 90 days.

- Any clinically significant abnormality of liver function test (ALT, AP, total

bilirubin >= 1. 5 ULN).

- Any clinically significant abnormality of renal function test (serum creatinine

concentration > 1. 4 mg/dL).

- Positive hepatitis B surface antigen (HBsAg), anti-HCV, or anti-HIV.

- Clinically significant hematology abnormalities.

- Clinically significant electrocardiogram (ECG) abnormalities.

- Any surgical or medical condition which might significantly alter the absorption,

distribution, metabolism, or excretion of the study drug.

- Past history of anaphylaxis or angioedema.

- History of drug or alcohol abuse within 12 months prior to screening.

- Participation in any clinical trial within the past 90 days.

- History of any bleeding or coagulative disorders.

- History of difficulty with donating blood or accessibility of veins in left or right

arm.

- A donation or loss of 500 mL (or more) of blood within 3 months before the study's

first dosing day.

- Intake of any prescription or non-prescription drugs, food supplements, or herbal

medicines within 14 days of the study's first dosing day.

PT Equilab International, Jakarta 12430, Indonesia

Starting date: February 2013
Last updated: September 1, 2013