Clinical trial NCT03210025: Clinical Bioequivalence Study on Two Methyldopa Tablet 250mg Formulations
Official title: Clinical Bioequivalence Study on Two Methyldopa Tablet 250mg Formulations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Bright Future Pharmaceuticals Factory O/B Bright Future Pharmaceutical Laboratories Limited
Sponsor class: INDUSTRY
Collaborators: name: Chinese University of Hong Kong
First posted: 2017-07-06
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single-dose, two-treatment, two-period, two-sequence crossover
Primary purpose: OTHER

Brief summary: The objective of the study is to compare the bioavailability of a generic product of methyldopa with that of a reference product when administered to healthy volunteers under fasting condition. The test product is BF-Methyldopa Tablet 250mg (HK Reg. No. HK-62917) manufactured by Bright Future Pharmaceuticals Factory O/B Bright Future Pharmaceutical Laboratories Limited, and the reference product is Metopa Tab 250mg (HK Reg. No. HK-44620). The plasma pharmacokinetic data of Methyldopa obtained from two formulations will be used to access the interchangeability of the products.

Detailed description: It is planned to enroll 16 to 30 healthy subjects, with an aim to obtain at least 12 evaluable subjects. The study design is a single-dose, two-treatment, two-period, two-sequence crossover with a washout period of one to two weeks. During each study session, the subjects will be administered a single oral dose of 250mg methyldopa (one BF-Methyldopa Tablet 250mg or one Metopa Tab 250mg) after an overnight fast of approximately 10 hours. Venous blood samples will be collected at pre-dose (0h) and at 0.75 (45min), 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 and 24 hours post-dose. The plasma concentrations of methyldopa 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. Anylasis of variance (ANOVA) will be conducted on logarithmically transformed Cmax, AUC0-last and AUC0-inf using the General Linear Model. The two one-side 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.

Eligibility criteria: Inclusion Criteria:

* Male and non-pregnant female, 18 to 55 years of age
* Body Mass Index between 18 to 27 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 screening until two weeks of last dose administration.

Exclusion Criteria:

* Clinical significant hepatic, renal, biliary, cardiovascular, gastrointestinal, haematological and other chronic and acute diseases within 3 months prior to the study
* Clinical significant abnormality in physical examination, vital signs, ECG evaluation, urine test, blood chemistry or haematological test
* Tobacco use in any forms
* Regular consumer of alcohol
* Blood donation within 4 weeks prior to the start of the study
* Use of Methyldopa within 4 weeks before the study
* Use of antihypertensive medications within 4 weeks before the study
* Volunteer in any other clinical drug study within 2 months prior to this study
* Hypersensitivity to Methyldopa or other drugs in its class
* History of drug abuse in any form
* Female subjects who are breastfeeding or pregnant.

Primary outcomes:
measure: Cmax of Methyldopa
timeFrame: 24 hours
measure: AUC of Methyldopa
timeFrame: 24 hours
Secondary outcomes:
measure: Tmax of Methyldopa
timeFrame: 24 hours
measure: Elimination half-life (t1/2) of Methyldopa
timeFrame: 24 hours
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong
Study officials:
affiliation: School of Pharmacy, The Chinese University of Hong Kong
name: Zhong Zuo
role: PRINCIPAL_INVESTIGATOR
affiliation: Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong
name: Riza Ozaki
role: STUDY_DIRECTOR
affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong
name: Brian Tomlinsion
role: STUDY_DIRECTOR
References: