Bioequivalence Study of Lisinopril Tablets 40 mg Under Fed Condition

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 Fed Conditions.

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 fed condition in normal, healthy, adult, male and female human subjects.

Study Overview

• Status: Completed
• Conditions: Fed
• Intervention / Treatment: Drug: Lisinopril Tablets 40 mg; Drug: Lisinopril

Detailed Description

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 fed 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 18 days including washout period of 14 days between administrations of study drug in each study period.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Navi-Mumbai, Gujarat, India
      • Accutest Research Lab (I) Pvt. Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and non pregnant female human subjects, age in the range of 18 - 45 years.
2. Body weight within ± 15% of ideal weight as related to height and body frame according to Life Insurance Corporation (LIC) Chart.
3. Subjects with normal findings as determined by baseline history, physical examination and vital sign examination (blood pressure, pulse rate, respiration rate and axillary temperature).
4. Subjects with clinically acceptable findings as determined by haemogram, biochemistry, urinalysis and 12 lead ECG.
5. 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.
6. No history of significant alcoholism.
7. No history of drug abuse (benzodiazepines and barbiturates) for the last one month and other illegal drugs for the last 6 months.
8. Non-smokers were included.

Exclusion Criteria:

1. Known history of hypersensitivity to Lisinopril or related drugs.
2. Requiring medication for any ailment having enzyme-modifying activity in the previous 28 days, prior to dosing day.
3. Subjects who have taken prescription medications or over-the-counter products (including vitamins and minerals) within 14 days prior to administration of Investigational Product.
4. Any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract, blood-forming organs etc.
5. History of cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic, haematological, gastrointestinal, endocrine, immunological or psychiatric diseases.
6. Participation in a clinical drug study or bioequivalence study 90 days prior to present study.
7. History of malignancy or other serious diseases.
8. Blood donation 90 days prior to the commencement of the study.
9. Subjects with positive HIV tests, HBsAg or Hepatitis-C tests.
10. Found positive in breath alcohol test.
11. Found positive in urine test for drug abuse.
12. History of problem in swallowing.
13. Any contraindication to blood sampling.
14. Found positive serum Beta- hCG (Human Chorionic Gonadotropin) test.
15. Lactating women (currently breast feeding).
16. 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.
17. Female subjects whose menstruation cycle coincided with the study periods.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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 hrs 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 hrs post dose.	2 months

Collaborators and Investigators

• Sponsor: IPCA Laboratories Ltd.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: November 5, 2012
• First Submitted That Met QC Criteria: November 23, 2012
• First Posted (Estimate): November 28, 2012

Study Record Updates

• Last Update Posted (Estimate): December 3, 2012
• Last Update Submitted That Met QC Criteria: November 30, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Cardiotonic Agents; Angiotensin-Converting Enzyme Inhibitors; Lisinopril
• Other Study ID Numbers: Ipca/ARL-10/385