Bioequivalence Study of Metformin Hydrochloride 500 mg Film-Coated Tablets in Indonesia Healthy Subject

The objective of this present study was to investigate whether Glufor® 500 (metformin hydrochloride 500 mg) film-coated tablets manufactured by PT. Pyridam Farma Tbk is bioequivalent to its reference product, Glucophage® 500 mg film-coated tablets manufactured by PT. Merck Tbk, Indonesia under licensed Merck Sante SAS, France.

Study Overview

• Status: Completed
• Conditions: Drug Use
• Intervention / Treatment: Drug: Metformin Hydrochloride 500 MG

Detailed Description

Twenty-four subjects were given a single dose of 500 mg Metformin film-coated tablet of either formulation (test or reference) with 240 mL of a 20% glucose solution in water.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10520
      • PT Pharma Metric Labs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 52 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

The inclusion criterias were healthy male or female subjects who/with:

• had read the subject information and signed informed consent documents
• age range from 18 - 55 years
• body mass index between 18 - 25 kg/m2
• had a normal electrocardiogram
• had the blood pressure within normal range (systolic 90-120 mmHg and diastolic 60-80 mmHg)
• had the heart rate within normal range (60 - 100 bpm)
• had absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening.

Exclusion criterias

The subjects' exclusion criterias for the study were:

• those who were pregnant and/or nursing women.
• those with history of contraindication or hypersensitivity to metformin or other antidiabetic agent or other ingredients in the study products or a history of serious allergic reaction to any drug, a significant allergic disease, or allergic reaction.
• those with a history or presence of medical condition which might significantly influence the pharmacokinetic of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease.
• those with a history or presence of any coagulation disorder or clinically significant hematology abnormalities.
• those who were using any medication (prescription or non-prescription drug, food supplement, herbal medicine), particularly the medication known to affect the pharmacokinetic of the study drug, within one week prior to the drug administration day.
• those who had participated in any clinical study within 3 months prior to the study (<90 days).
• those who had donated or lost 300 ml (or more) of blood within 3 months prior to the study.
• those who smoked more than 10 cigarettes a day
• those with a history of travelling to another city within the last 14 days
• those with a history of direct contact with a COVID-19 positive person in the subject's neighbourhood
• those with a history or present of sore throat, fever (with temperature more than 37°C) or dyspnea with in the last 14 days
• those who are positive to SARS CoV-2 antigen test
• those who were positive to HIV, HBsAg, and HCV tests (to be kept confidential).
• those with a history of drug or alcohol abuse within 12 months prior to screening for this study.
• those who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits, poor venous access.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glufor® 500 mg film-coated tablet	Drug: Metformin Hydrochloride 500 MG; Metformin is an antihyperglycemic drug used in the management of type-2 diabetes. Metformin hydrochloride improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Active Comparator: Glucophage® 500 mg film-coated tablet	Drug: Metformin Hydrochloride 500 MG; Metformin is an antihyperglycemic drug used in the management of type-2 diabetes. Metformin hydrochloride improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Ratio	The ratio between maximum concentration of test drug and reference drug after drug administration	0-24 hours post dose
Geometric Mean Ratio	The ratio between area under curve from 0 to 24 hours of test drug and reference drug	0-24 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics Parameter	Maximum plasma concentration (Cmax)	0-24 hours post dose
Pharmacokinetics Parameter	Area Under Curve from 0 to 24 hours (AUCt)	0-24 hours post dose

Collaborators and Investigators

• Sponsor: PT. Pyridam Farma Tbk
• Collaborators: PT Pharma Metric Labs
• Investigators: Principal Investigator: Frans D Suyatna, PT Pharma Metric Labs

Publications and helpful links

General Publications

• Al Hawari S, AlGaai E, Yusuf A, Abdelgaleel A, Hammami MM. Bioequivalence study of two metformin formulations. Arzneimittelforschung. 2007;57(4):192-5. doi: 10.1055/s-0031-1296605.
• Batolar LS, Iqbal M, Monif T, Khuroo A, Sharma PL. Bioequivalence and pharmacokinetic comparison of 3 metformin extended/sustained release tablets in healthy Indian male volunteers. Arzneimittelforschung. 2012 Jan;62(1):22-6. doi: 10.1055/s-0031-1295428. Epub 2012 Jan 10.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2022
• Primary Completion (Actual): March 24, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: February 12, 2023
• First Submitted That Met QC Criteria: February 21, 2023
• First Posted (Estimate): March 3, 2023

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: February 21, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Bioequivalence study; Indonesian healthy subject; Metformin hydrochloride 500 mg
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 634/STD/PML/2021

Drug and device information, study documents

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