Bioequivalence Study of Bisoprolol Fumarate Tablet 10 mg Under Fasting Condition

A Randomized, Open Label, Balanced, Two-Treatment, Two-Period, Two-Sequence, Single Dose, Crossover, Bioequivalence Study of Bisoprolol Fumarate Tablet 10 mg of With Zebeta® 10 mg in Normal, Healthy, Adult, Human Subjects Under Fasting Condition.

This is a randomized, open Label, balanced, 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 human subjects.

Study Overview

• Status: Completed
• Conditions: Fasting
• Intervention / Treatment: Drug: Bisoprolol Fumarate Tablet 10 mg; Drug: Bisoprolol

Detailed Description

Objective of this pivotal study was to assess the bioequivalence between Test Product: Bisoprolol Fumarate Tablet 10 mg of Ipca Laboratories Limited, India and the corresponding Reference Product: Zebeta® (Bisoprolol Fumarate) Tablets 10 mg of Duramed Pharmaceuticals Inc., USA under fasting condition in normal, healthy, adult, human subjects in a randomized crossover study.

The study was conducted with 24 healthy adult subjects. In each study period, a single 10 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 15 days including washout period of at least 10 days between administrations of study drug in each study period.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Ahmedabad, Gujarat, India
      • Accutest Research Lab (I) Pvt. Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and Non-pregnant female human subjects, age in the range of 18 - 45 years (both inclusive).
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 signs (blood pressure, pulse rate, respiration rate and oral temperature).
4. Subjects with clinically acceptable findings as determined by haemogram, biochemistry, serology (HIV, Hepatitis B and Hepatitis C), urinalysis, 12 lead ECG and chest X-ray (chest X-ray if required).
5. Willingness to follow the protocol requirements as evidenced by written informed consent.
6. Subject willing to give written informed consent.
7. Confirming and agreeing to, not using any prescription and over the counter medications including vitamins and minerals for 14 days prior to study and during the course of the study.
8. No history of drug abuse in the past one year.
9. Non-smokers and non-alcoholics.

10. For female subject

    • was child bearing potential practicing acceptable method of birth control for the duration of the study as judged by Investigator such as Condom, Foams, Jellies, Diaphragm, Intrauterine device and Abstinence.

OR

• was surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy has been performed on the subject).

Exclusion Criteria:

1. Known history of hypersensitivity to Bisoprolol Fumarate, or related drugs.
2. Requiring medication for any ailment having enzyme-modifying activity in the previous 28 days, prior to dosing day.
3. Any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract, blood-forming organs etc.
4. History of cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic, hematological, gastrointestinal, endocrine, immunological or psychiatric diseases and bleeding tendency.
5. Participation in a clinical drug study or bioequivalence study within 90 days prior to present study.
6. History of malignancy or other serious diseases.
7. Refusal to abstain from food for at least 10.00 hours prior to study drug administration and for at least 04.00 hours post-dose, in each study period.
8. Any contraindication to blood sampling or difficulty in accessibility of veins.
9. Refusal to abstain from fluid for at least 01.00 hour prior to study drug administration and for at least 01.00 additional hour post-dose, in each study period except about 240 mL of water given during administration of study drug.
10. Refusal to avoid the use of xanthine-containing food or beverages (chocolates, tea, coffee or cola drinks) or fruit juice/grapefruit juice and any alcoholic products for 48.00 hours prior to dosing until the last blood sample collection of last study period.
11. Blood donation within 90 days prior to the commencement of the study.
12. Subjects with positive HIV tests or Hepatitis-B or Hepatitis-C tests.
13. Found positive in breath alcohol test done before check-in for each study period.
14. Found positive in urine test for drugs of abuse done before check-in for each study period.
15. Refusal to abstain from consumption of tobacco products 24.00 hours prior to dosing until the last blood sample collection of last study period.
16. History of problem in swallowing Tablet(s).
17. Female subject, demonstrating positive urine pregnancy test at the time of screening.
18. Female subject, demonstrating positive Serum (ß) Beta- hCG (Human Chorionic Gonadotropin) test before check-in for each study period.
19. Female subject, currently breast feeding or lactating.
20. Female subjects not willing to use acceptable method of contraception from the date of screening until the completion of the study.

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: Bisoprolol Fumarate Tablet 10 mg; Bisoprolol Fumarate Tablet 10 mg of M/s Ipca Laboratories Limited, India	Drug: Bisoprolol Fumarate Tablet 10 mg; 10 mg tablet once a day; Other Names: Test Product
Active Comparator: Zebeta®; Zebeta® (Bisoprolol Fumarate) Tablets 10 mg of Duramed Pharmaceuticals Inc., USA	Drug: Bisoprolol; 10 mg tablet once a day; Other Names: Zebeta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	pre-dose, 00.50, 01.00, 01.50, 02.00, 02.33, 02.67, 03.00, 03.33, 03.67, 04.00, 04.50, 05.00, 06.00, 07.00, 08.00, 10.00, 12.00, 16.00, 20.00, 24.00, 48.00 and 72.00 hours post-dose	3 months
AUC	Pre-dose and at 00.50, 01.00, 01.50, 02.00, 02.33, 02.67, 03.00, 03.33, 03.67, 04.00, 04.50, 05.00, 06.00, 07.00, 08.00, 10.00, 12.00, 16.00, 20.00, 24.00, 48.00 and 72.00 hours post-dose.	3 months

Collaborators and Investigators

• Sponsor: IPCA Laboratories Ltd.
• Investigators: Principal Investigator: Dr. Rupesh Vala, M.B.B.S., Accutest Research Lab (I) Pvt. Ltd.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: December 1, 2012
• First Submitted That Met QC Criteria: December 1, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Estimate): December 5, 2012
• Last Update Submitted That Met QC Criteria: December 1, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Bisoprolol
• Other Study ID Numbers: Ipca/ARL-12/147