Bioequivalence Study of Lisinopril Tablets 40 mg Under Fasting Condition

Study Overview
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Brief Summary
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This is a randomized, balanced, open Label, two-treatment, two-period, two-sequence, single dose, crossover pivotal study. The purpose of this study is to assess the bioequivalence between Test Product and the corresponding Reference Product under fasting condition in normal, healthy, adult, male and female human subjects.

Detailed Description
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Objective of this pivotal study was to assess the bioequivalence between Test Product: Lisinopril Tablets 40 mg of Ipca Laboratories Limited, India and the corresponding Reference Product: Zestril® (Lisinopril) 40 mg Tablets of AstraZeneca Pharmaceuticals LP USA, under fasting condition in normal, healthy, adult, male and female human subjects in a randomized crossover study. The study was conducted with 40 healthy adult subjects. In each study period, a single 40 mg dose of either test or reference was administered to the subjects as per the randomization schedule in each study period with about 240 mL of water at ambient temperature in sitting position. The duration of the clinical phase was approximately 19 days including washout period of 15 days between administrations of study drug in each study period.

Official Title
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A Randomized, Balanced, Open Label, Two Treatment, Two Period, Two Sequence, Single Dose, Crossover, Bioequivalence Study of Lisinopril Tablets 40 mg With Zestril® (Lisinopril) 40 mg Tablets in Normal, Healthy, Adult, Male and Female Human Subjects Under Fasting Conditions.

Conditions
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Fasting

Intervention / Treatment
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* Drug: Lisinopril Tablets 40 mg
* Drug: Lisinopril


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non pregnant female human subjects, age in the range of 18 - 45 years. Body weight within ± 15% of ideal weight as related to height and body frame according to Life Insurance Corporation (LIC) Chart. Subjects with normal findings as determined by baseline history, physical examination and vital sign examination (blood pressure, pulse rate, respiration rate and axillary temperature). Subjects with clinically acceptable findings as determined by haemogram, biochemistry, urinalysis and 12 lead ECG. Willingness to follow the protocol requirements especially abstaining from xanthine containing food or beverages (chocolates, tea, coffee or cola drinks) or grapefruit juice, any alcoholic products, the use of cigarettes and tobacco products for 48 hours prior to dosing until after the last blood sample collection in each study period and adherence to food, fluid and posture restrictions. No history of significant alcoholism. No history of drug abuse (benzodiazepines and barbiturates) for the last one month and other illegal drugs for the last 6 months. Non-smokers were included. Exclusion Criteria: Known history of hypersensitivity to Lisinopril or related drugs. Requiring medication for any ailment having enzyme-modifying activity in the previous 28 days, prior to dosing day. Subjects who have taken prescription medications or over-the-counter products (including vitamins and minerals) within 14 days prior to administration of Investigational Product. Any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract, blood-forming organs etc. History of cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic, haematological, gastrointestinal, endocrine, immunological or psychiatric diseases. Participation in a clinical drug study or bioequivalence study 90 days prior to present study. History of malignancy or other serious diseases. Blood donation 90 days prior to the commencement of the study. Subjects with positive HIV tests, HBsAg or Hepatitis-C tests. Found positive in breath alcohol test. Found positive in urine test for drug abuse. History of problem in swallowing. Any contraindication to blood sampling. Found positive serum Beta- hCG (Human Chorionic Gonadotropin) test. Lactating women (currently breast feeding). Female subjects not confirming to using birth control measures, from the date of screening until the completion of the study. Abstinence, barrier methods (condom, diaphragm, etc.) were acceptable. Use of hormonal contraceptives either oral or implants. Female subjects whose menstruation cycle coincided with the study periods.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lisinopril Tablets 40 mg<br>Lisinopril Tablets 40 mg of Ipca Laboratories Limited, India | Drug: Lisinopril Tablets 40 mg<br>* 40 mg tablet once a day<br>* Other names: Test Product;|
| Active Comparator: Zestril® (Lisinopril) 40 mg Tablets<br>Zestril® (Lisinopril) 40 mg Tablets of AstraZeneca Pharmaceuticals LP USA | Drug: Lisinopril<br>* 40 mg tablet once a day<br>* Other names: Zestril® (Lisinopril) 40 mg Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Sampling Hours: Pre-dose and at 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.25, 6.50, 6.75, 7.00, 7.25, 7.50, 7.75, 8.00, 8.50, 9.00, 10.00, 12.00, 16.00, 24.00, 48.00 and 72.00 hours post dose | 2 months | 
| AUC | Sampling Hours: Pre-dose and at 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.25, 6.50, 6.75, 7.00, 7.25, 7.50, 7.75, 8.00, 8.50, 9.00, 10.00, 12.00, 16.00, 24.00, 48.00 and 72.00 hours post dose | 2 months |