Clinical Bioequivalence Study on Two Metoprolol Tablet 100mg Formulations

The purpose of the study is to compare the bioavailability of a generic product of metoprolol with that of a reference product when administered to healthy volunteers under fasting conditions. The test product is BF-Metoprolol Tablets 100mg manufactured by Bright Future Pharmaceuticals Factory O/B Bright Future Pharmaceutical Laboratories Limited and the reference product is Betaloc Tablet 100mg. The plasma kinetic data of metoprolol obtained from two formulations will be used to access the interchangeability of the products.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Drug: BF-Metoprolol Tablet 100mg; Drug: Betaloc Tablet 100mg

Detailed Description

The study design is a single-dose, two-treatment, two-period, two-sequence cross over with a washout period of one to two weeks. Subject will be randomly assigned to two groups corresponding to two dosing sequences. Each subject will undergo two study (treatment) sessions, during which a single oral dose of 100mg metoprolol from either test or reference formulations will be administered. The estimated duration of subject's participation will be about 29-36 days (i.e. 3 weeks for screening and medication restraint, 1 day each for study (treatment) sessions I and II, 1 - 2 weeks as washout period. Venous blood samples will be collected at pre-dose (0h), and up to 24h post dose. The plasma concentrations of metoprolol will be determined by a validated assay. The non-compartmental method will be used to analyze the plasma concentration-time data and calculate the main pharmacokinetic parameters such as Cmax, Tmax, AUC0-last, AUC0-inf, and T1/2. ANOVA will be calculated on logarithmically transformed Cmax, AUC0-last and AUC0-inf. The two one sided tests will be used to calculate the 90% confidence intervals for the mean difference in AUC0-last, AUC0-inf and Cmax and to assess the bioequivalence of the two products

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and non-pregnant female, 18 to 55 years of age
• Body Mass Index between 18 to 30 kg/m2
• Accessible vein for blood sampling
• High probability for compliance and completion of the study
• Female subjects must agree to practice abstinence or take effective contraceptive methods to prevent pregnancy from the start of the screening and until two weeks of last dose administration

Exclusion Criteria:

• Clinically significant hepatic, renal, biliary, cardiovascular, gastrointestinal, haematological and other chronic and acute diseases within 3 months prior to the study
• Clinically significant abnormality in physical examination, vital sign, laboratory test results, ECG evaluation, urine test, blood chemistry or haematological test
• Regular consumption of tobacco used in any forms
• Regular consumer of alcohol (more than one drink per day)
• Blood donation within 4 weeks prior to the start of the study
• Use of metoprolol within 4 weeks before the study
• Use of antihypertensive medications or other beta blockers within 4 weeks before the study
• Volunteer in any other clinical drug study within 2 months prior to this study
• Hypersensitivity to metoprolol or other drugs in its class
• History of drug abuse in any form
• Female subjects who are breastfeeding or pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BF-Metoprolol Tablet 100mg; During the study session, healthy subjects will be administered a single dose of BF-Metoprolol Tablet 100mg after an overnight fast of approximately 10 hours	Drug: BF-Metoprolol Tablet 100mg; BF-Metoprolol Tablet 100mg is a generic product manufactured by Bright Future Pharmaceuticals Factory O/B Bright Future Pharmaceutical Laboratories Limited; Other Names: Metoprolol Tablet 100mg
Active Comparator: Betaloc Tablet 100mg; During the study session, healthy subjects will be administered a single dose of Betaloc Tablet 100mg after an overnight fast of approximately 10 hours	Drug: Betaloc Tablet 100mg; Betaloc Tablet 100mg will be used as a comparator drug for the BE study; Other Names: Metoprolol Tablet 100mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak plasma concentration (Cmax) of metoprolol	24 hours
Area under the plasma concentration versus time curve (AUC) of metoprolol	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to maximum concentration (Tmax) of metoprolol	24 hours
Elimination half-life (t1/2) of metoprolol	24 hours

Collaborators and Investigators

• Sponsor: Bright Future Pharmaceuticals Factory O/B Bright Future Pharmaceutical Laboratories Limited
• Collaborators: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2020
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: March 12, 2017
• First Submitted That Met QC Criteria: March 12, 2017
• First Posted (Actual): March 17, 2017

Study Record Updates

• Last Update Posted (Actual): July 29, 2019
• Last Update Submitted That Met QC Criteria: July 25, 2019
• Last Verified: July 1, 2019

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; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: BABE-P15-100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Study investigators and his/her study team members, domestic and foreign regulatory agencies, the IRB/EC involved in the study, and laboratories and other individuals and organizations that analyze the subjects' protected health information in connection with this study have access to the data or study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No