Clinical Bioequivalence Study on Two Methyldopa Tablet 250mg Formulations

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical Bioequivalence Study on Two Methyldopa Tablet 250mg Formulations

Conditions
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Healthy

Intervention / Treatment
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* Drug: BF-Methyldopa 250mg Tablet
* Drug: Metopa Tab 250mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single-dose, two-treatment, two-period, two-sequence crossover
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BF-Methyldopa Tablet 250mg<br>During the study session, healthy subjects will be administered a single dose of BF-Methyldopa Tablet 250mg after an overnight fast of approximately 10 hours | Drug: BF-Methyldopa 250mg Tablet<br>* BF-Methyldopa 250mg Tablet is a generic product manufactured by Bright Future Pharmaceuticals Factory O/B Bright Future Pharmaceutical Laboratories Limited<br>* Other names: Methyldopa 250mg Tablet;|
| Active Comparator: Metopa Tab 250mg<br>During the study session, healthy subjects administered a single dose of Metopa Tablet 250mg after an overnight fast of approximately 10 hours | Drug: Metopa Tab 250mg<br>* Metopa Tab 250mg is manufactured by APT<br>* Other names: Methyldopa 250mg Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Methyldopa |  | 24 hours | 
| AUC of Methyldopa |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax of Methyldopa |  | 24 hours | 
| Elimination half-life (t1/2) of Methyldopa |  | 24 hours |