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

Healthy Clinical Trial

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.)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01936012
• Other study ID #: BE.258/EQL/2012
• Status: Completed
• Phase: N/A
• First received: September 1, 2013
• Last updated: September 1, 2013
• Start date: February 2013
• Est. completion date: February 2013

Study information

• Verified date: September 2013
• 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 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.)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• 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.

• 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.

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:
• Lisinopril 10 mg tablets of PT Dexa Medica
Each tablet contains 10.89 mg of lisinopril dihydrate that equal to 10 mg lisinopril. Test product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.
• Lisinopril 10 mg tablets of PT Boehringer Ingelheim Indonesia
Each tablet contains 10.89 mg of lisinopril dihydrate that equal to 10 mg lisinopril. 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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve from time zero to the last observed quantifiable concentration (AUCt) of lisinopril	Relative bioavailability (primarily measured by AUCt and AUCinf) between two lisinopril 10 mg tablet formulations (test and reference formulations) was assessed under fasting condition. AUCt was determined from plasma concentration of lisinopril.	48 hours	No
Primary	Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of lisinopril	Relative bioavailability (primarily measured by AUCt and AUCinf) between two lisinopril 10 mg tablet formulations (test and reference formulations) was assessed under fasting condition. AUCinf was determined from plasma concentration of lisinopril.	48 hours	No
Secondary	The peak plasma concentration (Cmax) of lisinopril	Relative bioavailability (secondarily measured by Cmax) between two lisinopril 10 mg tablet formulations (test and reference formulations) was assessed under fasting condition. Cmax was determined from plasma concentration of lisinopril.	48 hours	No
Secondary	Time needed to achieve the peak plasma concentration (t max) of lisinopril	Relative bioavailability (secondarily measured by t max) between two lisinopril 10 mg tablet formulations (test and reference formulations) was assessed under fasting condition. t max was determined from plasma concentration of lisinopril.	48 hours	No
Secondary	The elimination half-life (t1/2) of lisinopril	Relative bioavailability (secondarily measured by t1/2) between two lisinopril 10 mg tablet formulations (test and reference formulations) was assessed under fasting condition. t1/2 was determined from plasma concentration of lisinopril.	48 hours	No