A Relative Bioavailability Study of Carvedilol 12.5 mg Tablets Under Non-fasting Conditions

A Two-Way Crossover, Open-Label, Single Dose, Fed, Bioequivalence Study of Carvedilol 12.5 mg Tablets Versus Coreg® 12.5 mg Tablets in Normal, Healthy, Non-Smoking Male and Female Subjects

To compare the rate and extent of absorption of carvedilol from a test formulation of Carvedilol 12.5 mg Tablets versus the reference Coreg® 12.5 mg Tablets under fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Carvedilol 12.5 mg Tablets, single dose; Drug: Coreg® 12.5 mg Tablets , single dose

Detailed Description

Study Type: Interventional Study Design: Two-way crossover, randomized, open-label, single-dose, fed, bioequivalence study

Official Title: A Two-Way Crossover, Open-Label, Single Dose, Fed, Bioequivalence Study of Carvedilol 12.5 mg Tablets Versus Coreg® 12.5 mg Tablets in Normal, Healthy, Non-Smoking Male and Female Subjects

Further study details as provided by Actavis Elizabeth LLC:

Primary Outcome Measures:

Rate and Extend of Absorption

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M1L 4S4 / M1L 4R6
      • Biovail Contract Research (A Division of Biovail Corporation)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Non-smoking male or female with a minimum age of 18 years.
2. Body Mass Index (BMI = weight/heigh2) greater than or equal to 18.5 kg/m2 and less than or equal to 29.9 kg/m2
3. Normal findings in the physical examination, 12-lead ECG and vital signs (blood pressure between 106-140/66-90 mmHg, heart rate between 60-99 beats/minute, temperature between 35.8°C and 37.5°C)
4. Negative for drugs of abuse and nicotine.
5. Negative for hepatitis B-surface antigen, hepatitis C and HIV.
6. Female subjects: negative for pregnancy (as evaluated by serum ß-CG test).
7. No clinical laboratory values outside of the acceptable range as defined by BCR, unless the Principal Investigator decides that they are not clinically significant.
8. Female subjects who were surgically sterile for at least 6 months or post-menopausal for at least 1 year, or avoided pregnancy for at least 10 days before the study, during the study and up until 1 month after the end of the study.
9. Availability of the subject for the entire study period and willingness of the subject to adhere to protocol requirements, as evidenced by a signed ICF

Exclusion Criteria:

1. Known history of hypersensitivity to carvedilol (e.g. Coreg®) and/or related beta¬blockers such as propranolol (Inderal®, nadolol (Corgard®), labetalol (Trandate®, metoprolol (Lopressor®, Betaloc®, atenolol (Tenormin®, sotalol, timolol, pindolol, or acebutolol.
2. Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, hematological, liver or kidney disease, unless deemed not clinically significant by the Principal Investigator or Sub-investigator.
3. Presence of any significant physical or organ abnormality.
4. Any history or evidence of psychiatric or psychological disease (including depression) unless deemed not clinically significant by the Principal Investigator or Sub-investigator.
5. Known history of frequent headaches or migraines.
6. Known history of chronic bronchitis or any bronchospastic condition.
7. Any clinically significant illness during the 4 weeks before this study.
8. Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
9. Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens).
10. Significant or recent history of asthma (after 12 years of age).
11. Any subject with a history of drug abuse.
12. Any subject with a recent (less than 1 year) history of alcohol abuse.
13. Use of any prescription medication within 14 days preceding this study.
14. Use of any over-the-counter (OTC) cough and cold medication containing dextromethorphan within 14 days preceding this study.
15. Use of OTC medication within 7 days preceding this study (except for spermicidal/barrier contraceptive products).
16. Female subjects: use of contraceptives (oral, emergency [plan B®, transdermal, implant, Mirena® IUD, NuvaRing®) within 30 days before drug administration or a depot injection of progestogen drug (e.g. Depo-Provera® within 1 year before drug administration.
17. Female subjects: evidence of pregnancy or lactation.
18. Any subject who had blood drawn within 56 days preceding this study, during the conduct of any clinical study at a facility other than BCR, or within the lockout period specified by a previous study conducted at BCR.
19. Participated in a clinical trial with an investigational drug within 30 days preceding this study.
20. Any subject who had donated blood within 56 days preceding this study.
21. Any subject who had participated as a plasma donor in a plasmapheresis program within 7 days preceding this study.
22. Intolerance to venipuncture.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Carvedilol 12.5 mg Tablets, single dose	Drug: Carvedilol 12.5 mg Tablets, single dose; A: Experimental Subjects received Shasun Chemicals and Drugs Ltd. formulated products under fed conditions; Other Names: Carvedilol
Active Comparator: B; Coreg® 12.5 mg Tablets , single dose	Drug: Coreg® 12.5 mg Tablets , single dose; B: Active comparator Subjects received GlaxoSmithKline, USA formulated products under fed conditions; Other Names: Carvedilol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate and Extend of Absorption	36 hours

Collaborators and Investigators

• Sponsor: Actavis Inc.
• Investigators: Principal Investigator: Paul Y. Tam,, M.D, Biovail Contract Research

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): November 1, 2005
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (Estimate): March 18, 2009

Study Record Updates

• Last Update Posted (Estimate): August 16, 2010
• Last Update Submitted That Met QC Criteria: August 13, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy subjects; Carvedilol
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: 3166