Clinical Bioequivalence Study on Two Lisinopril Tablets 20mg Formulations

Phase 1

• Conditions: Healthy
• Interventions: Drug: BF-Lisinopril Tablets 20mg; Drug: Zestril Tab 20mg

• Registration Number: NCT03599466
• Lead Sponsor: Bright Future Pharmaceuticals Factory O/B Bright Future Pharmaceutical Laboratories Limited

Brief Summary

The objective of the study is to compare the bioavailability of a generic product of lisinopril with that of a reference product when administered to healthy volunteers under fasting condition. The test product is BF-Lisinopril Tablet 20mg (HK-63564) manufactured by Bright Future Pharmaceuticals Factory O/B Bright Future Pharmaceutical Laboratories Limited, and the reference product is Zestril Tab 20mg (HK-30515). The bioequivalence or bioinequivalence of the test and reference formulations will be assessed and concluded based on the plasma pharmacokinetic data of lisinopril, as well as WHO guidelines on registration requirements to establish interchangeability.

Detailed Description

It is planned to enroll 16 to 30 healthy subjects, with an aim to obtain at least 12 evaluable subjects. The study design is a single-dose, two-treatment, two-period, two-sequence crossover with a washout period of one to two weeks. During each study session, the subjects will be administered a single dose of 20mg lisinopril (one BF-Lisinopril tablets 20mg or one Zestril Tab 20mg) after an overnight fast of approximately 10 hours. Venous blood samples will be collected at pre-dose (0h) and at 1,2,4,5,6,7,8,9,10,12,24 and 48 hours post-dose (13 time points). The plasma concentrations of lisinopril will be determined by a validated assay. The non-compartmental method will be used to analyze the plasma concentration-time data and calculate the main pharmacokinetic parameters such as Cmax, Tmax, AUC0-last, AUC0-inf, and T1/2. ANOVA will be calculated on logarithmically transformed Cmax, AUC0-last and AUC0-inf. The two one sided tests will be used to calculate the 90% confidence intervals for the mean difference in AUC0-last, AUC0-inf and Cmax and to assess the bioequivalence of the two products.

Study Timeline

• Study First Submitted: 2018-01-16
• Study First Submitted QC: 2018-07-16
• Study First Posted: 2018-07-26
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-14
• Last Update Posted: 2019-01-16
• Study Start: 2019-10
• Primary Completion: 2020-03
• Study Completion: 2020-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Male and non-pregnant female, 18 to 55 years of age
• Body Mass Index between 18 to 30 kg/m2
• Accessible vein for blood sampling
• High probability for compliance and completion of the study
• Female subjects must agree to practice abstinence or take effective contraceptive methods to prevent pregnancy from the start of the screening and until two weeks of last dose administration.

Exclusion Criteria

• Clinically significant hepatic, renal, biliary, cardiovascular, gastrointestinal, haematological and other chronic and acute diseases within 3 months prior to the study
• Clinically significant abnormality in physical examination, vital sign, laboratory test results, ECG evaluation, urine test, blood chemistry or haematological test
• Regular consumption of tobacco used in any forms
• Regular consumer of alcohol (more than one drink per day)
• Blood donation within 4 weeks prior to the start of the study
• Use of lisinopril within 4 weeks before the study
• Use of antihypertensive medications or angiotensin-converting enzyme (ACE) inhibitors within 4 weeks before the study
• Volunteer in any other clinical drug study within 2 months prior to this study
• Hypersensitivity to lisinopril or other drugs in its class
• History of drug abuse in any form
• Female subjects who are breastfeeding or pregnant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
BF-Lisinopril Tablets 20mg	BF-Lisinopril Tablets 20mg	During the study session, the subjects will be administered a single dose of BF-Lisinopril Tablet 20mg after an overnight fast of approximately 10 hours.
BF-Lisinopril Tablets 20mg	Zestril Tab 20mg	During the study session, the subjects will be administered a single dose of BF-Lisinopril Tablet 20mg after an overnight fast of approximately 10 hours.
Zestril Tab 20mg	BF-Lisinopril Tablets 20mg	During the study session, the subjects will be administered a single dose of Zestril Tab 20mg after an overnight fast of approximately 10 hours.
Zestril Tab 20mg	Zestril Tab 20mg	During the study session, the subjects will be administered a single dose of Zestril Tab 20mg after an overnight fast of approximately 10 hours.

Primary Outcome Measures

Name	Time	Method
Peak plasma concentration (Cmax) of Lisinopril	48 hours	Peak drug concentration, obtained directly from the original concentration-time data.
Area under the plasma concentration versus time curve (AUC) of Lisinopril	48 hours	Area under the concentration-time curve from time zero to the last sampling time.

Secondary Outcome Measures

Name	Time	Method
Time to maximum concentration (Tmax) of Lisinopril	48 hours	Time to peak drug concentration, obtained directly from the original concentration-time data.
Elimination half-life (t1/2) of Lisinopril	48 hours	Terminal elimination half-life, calculated as 0.693/(the terminal phase elimination rate constant that can be obtained using WinNonlin)