Fasting Study of Propranolol Hydrochloride Extended-Release Capsules 160 mg and Inderal® LA Capsules 160 mg

Single-Dose Fasting Bioequivalence Study of Propranolol Hydrochloride Extended-Release Capsules (160 mg; Mylan) and Inderal® LA Capsules (160 mg; Wyeth) in Healthy Volunteers

The objective of this study was to investigate the bioequivalence of Mylan's propranolol hydrochloride extended-release 160 mg capsules to Wyeth's Inderal LA® 160 mg capsules following a single, oral 160 mg (1 x 160 mg) dose administration under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Propranolol Hydrochloride Extended-Release Capsules 160 mg; Drug: Inderal® LA Capsules 160 mg

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • PRACS Institute, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age: 18 years and older.

2. Sex: Male and/or non-pregnant, non-lactating female.

   1. Women of childbearing potential must have a negative serum (Beta HCG) pregnancy test performed within 21 days prior to the start of the study and on the evening prior to each dose administration. If dosing is scheduled on Sunday or Monday, the HCG pregnancy test should be given within 48 hours prior to dosing for each study period. An additional serum (Beta HCG) pregnancy test will be performed upon completion of the study.

   2. Women of childbearing potential must practice abstinence or use an acceptable form of contraception throughout the duration of the study. No hormonal contraceptives or hormonal replacement therapies are permitted in this study. Acceptable forms of contraception include the following:

      1. intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or
      2. barrier methods containing or used in conjunction with a spermicidal agent, or
      3. surgical sterilization

   3. Women will not be considered of childbearing potential if one of the following is reported and documented on the medical history:

      1. postmenopausal with an absence of menses for at least one (1) year, or
      2. bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or
      3. total hysterectomy
   4. During the course of the study, from study screen until study exit - including the washout period, all men and women of childbearing potential must use a spermicide containing barrier method of contraception in addition to their current contraceptive method. This advice should be documented in the informed consent form.
3. Weight: At least 60 kg (132 lbs) for men and 48 kg (106 lbs) for women and all subjects within 15% of their Ideal Body Weight (IBW), as referenced by the Table of ""Desirable Weights of Adults"" Metropolitan Life Insurance Company, 1999 (See Part II ADMINISTRATIVE ASPECTS OF BIOEQUIVALENCE PROTOCOLS).
4. All subjects should be judged normal and healthy during a pre-study medical evaluation (physical examination, laboratory evaluation, hepatitis B and hepatitis C tests, HIV test, 12-lead ECG, and urine drug screen including amphetamine, barbiturates, benzodiazepines, cannabinoid, cocaine, opiate screen, phencyclidine, and methadone) performed within 21 days of the initial dose of study medication.

Exclusion Criteria:

1. Institutionalized subjects will not be used.

2. Social Habits:

   1. Use of any tobacco products within 1 year of the start of the study.
   2. Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication.
   3. Ingestion of any vitamins or herbal products within 7 days prior to the initial dose of the study medication.
   4. Any recent, significant change in dietary or exercise habits.
   5. A positive test for any drug included in the urine drug screen.
   6. History of drug and/or alcohol abuse.

3. Medications:

   1. Use of any prescription or over-the-counter (OTC) medications within the 14 days prior to the initial dose of study medication.
   2. Use of any hormonal contraceptives or hormone replacement therapy within 3 months prior to study medication dosing.
   3. Use of any medication known to alter hepatic enzyme activity within 28 days prior to the initial dose of study medication.

4. Diseases:

   1. History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, or neurologic disease.
   2. Acute illness at the time of the pre-study medical evaluation or dosing.
   3. A positive HIV, hepatitis B, or hepatitis C test.
   4. History of asthma or other pulmonary problems

5. Abnormal and clinically significant laboratory test results:

   1. Abnormal and clinically relevant ECG tracing.
   2. Clinically significant deviation from the Guide to Clinically Relevant Abnormalities (See Part II ADMINISTRATIVE ASPECTS OF BIOEQUIVALENCE PROTOCOLS).
6. Donation or loss of a significant volume of blood or plasma (> 450 mL) within 28 days prior to the initial dose of study medication.
7. Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.
8. Sitting pulse rate less than 60 beats per minute after a five minute rest at screening or prior to Period I Day 1 dosing.
9. Allergy or hypersensitivity to propranolol hydrochloride or other beta-adrenergic receptor-blocking agents.
10. History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption.
11. Consumption of grapefruit or grapefruit containing products within 7 days of drug administration.
12. Average sitting systolic blood pressure less than 95 mmHg or average sitting diastolic blood pressure less than 65 mmHg following a five (5) minute rest at screening or prior to Period I Day 1 dosing. Blood pressure measurements will be taken in triplicate with at least two (2) minutes elapsing in-between readings.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Propranolol Hydrochloride Extended-Release Capsules 160 mg	Drug: Propranolol Hydrochloride Extended-Release Capsules 160 mg; 160mg, single dose fasting
ACTIVE_COMPARATOR: 2; Inderal® LA Capsules 160 mg	Drug: Inderal® LA Capsules 160 mg; 160mg, single dose fasting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bioequivalence	within 30 days

Collaborators and Investigators

• Sponsor: Mylan Pharmaceuticals Inc

Publications and helpful links

Helpful Links

• Mylan Pharmaceuticals Inc. - Clinical Trial Results
• Daily Med - posting of most recent submitted labelling to the Food and Drug Administration (FDA) and currently in use
• Recalls, Market Withdrawals and Safety Alerts

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (ACTUAL): September 1, 2005
• Study Completion (ACTUAL): September 1, 2005

Study Registration Dates

• First Submitted: March 30, 2008
• First Submitted That Met QC Criteria: March 31, 2008
• First Posted (ESTIMATE): April 1, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 1, 2008
• Last Update Submitted That Met QC Criteria: March 31, 2008
• Last Verified: March 1, 2008

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; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: PRPL-05115