Bioequivalence Study of 4 mg Glimepiride Tablet

Bioequivalence Study of Two Formulations of Glimepiride Tablet in Healthy Subjects

This was a randomized, single blind, two-period, two sequence cross-over study under fasting condition to compare the bioavailability of two glimepiride 4 mg tablet formulations (test and reference formulations).

Study Overview

• Status: Completed
• Conditions: Glimepiride BE Study in Healthy Volunteers Under Fasting Condition
• Intervention / Treatment: Drug: Group I (Test) : Glimepiride 4 mg tablet of PT Dexa Medica; Drug: Group II (Reference) : glimepiride (Amaryl) 4 mg tablet of PT Sanofi Aventis

Detailed Description

The participating subjects were required to have an overnight fast; and in the next morning they were given orally either one tablet of 4 mg glimepiride as the test drug (produced by PT Dexa Medica) or one tablet of 4 mg glimepiride (Amaryl®, Sanofi Aventis) as the reference drug with 200 mL water.

Blood samples were drawn immediately before taking the drug (control), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 6, 9, 12, 18 and 24 hours after drug administration. Immediately after drug administration, subjects were administered 100 ml of 10% glucose at approximately 0.5, 1.5, 2, 2.5, 3.5, and 4.5 hours. In addition, 20% glucose solution was given to any subject who exhibited symptoms of hypoglycaemia. One week after the first drug administration (wash-out period), the procedure was repeated using the alternate drug.

The plasma concentrations of glimepiride were determined by high performance liquid chromatography with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed are AUCt, AUCinf, Cmax, tmax, and t1/2.

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

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 12430
    • PT Equilab International

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:

1. Male and female subjects with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening
2. Age of 18 - 55 years
3. Preferably non-smokers or moderate smokers (less than 10 cigarettes per day)
4. Able to participate, communicate well with the investigators and willing to provide written informed consent to participate in the study
5. BMI 18 - 25 kg/m2

6. Vital signs (after 10 minutes rest) must be within the following ranges:

   • SBP 100 - 120 mmHg
   • DBP 60 - 80 mmHg
   • Pulse rate 60 - 90 bpm

Exclusion Criteria:

1. Personal/family history of allergy or hypersensitivity or contraindication to glimepiride or allied drugs
2. Pregnant or lactating women
3. Any major illnesses in the past 90 days or clinically significant ongoing chronic medical illness
4. Presence of any clinically significant abnormal values during screening
5. Positive Hepatitis B surface antigen (HBsAg), anti-HCV, or anti-HIV
6. Clinically significant haematology abnormalities
7. Clinically significant electrocardiogram (ECG) abnormalities
8. Any surgical or medical condition (present or history) which might significantly alter the absorption, distribution, metabolism or excretion of the study drug
9. Past history of anaphylaxis or angioedema
10. History of drug or alcohol abuse within 12 months prior to screening
11. Participation in any clinical trial within the past 90 days
12. History of any bleeding or coagulative disorders
13. History of difficulty with donating blood or difficulty in accessibility of veins in left or right arm
14. A donation or loss of 500 mL (or more) of blood within 3 months before this study's first dosing day
15. Intake of any prescription, non-prescription drug, food supplements or herbal medicines within 14 days of this study's first dosing day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (Test); Test : glimepiride 4 mg tablet of PT Dexa Medica	Drug: Group I (Test) : Glimepiride 4 mg tablet of PT Dexa Medica; In each of the two study periods (separated by a washout of one week) a single dose of test or reference product was administered.
Active Comparator: Group II (Reference); Reference : glimepiride (Amaryl) 4 mg tablet of PT Sanofi-Aventis, Indonesia	Drug: Group II (Reference) : glimepiride (Amaryl) 4 mg tablet of PT Sanofi Aventis; In each of the two study periods (separated by a washout of one week) a single dose of test or reference product was administered.; Other Names: Amaryl®, manufactured by PT Sanofi Aventis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioavailability	Relative bioavailability (primarily measured by AUC and Cmax) between two glimepiride 4 mg tablet formulations (test and reference formulations) under fasting condition.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioavailability	Relative bioavailability (secondarily measured by tmax and t1/2) between two formulations of glimepiride 4 mg tablets (the Test and Reference formulations)	24 hours
Adverse events	The presence of adverse events will be observed, reported and sufficiently handled during subjects' participation in the study (1 month).	1 months

Collaborators and Investigators

• Sponsor: Dexa Medica Group
• Investigators: Principal Investigator: Danang A. Yunaidi, MD, PT. Equilab International

Publications and helpful links

General Publications

• Salem II, Idrees J, Al Tamimi JI. Determination of glimepiride in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jan 5;799(1):103-9. doi: 10.1016/j.jchromb.2003.10.024.
• Jovanovic D, Stojsic D, Zlatkovic M, Jovic-Stosic J, Jovanovic M. Bioequivalence assessment of the two brands of glimepiride tablets. Vojnosanit Pregl. 2006 Dec;63(12):1015-20. doi: 10.2298/vsp0612015j.
• Malerczyk V, Badian M, Korn A, Lehr KH, Waldhausl W. Dose linearity assessment of glimepiride (Amaryl) tablets in healthy volunteers. Drug Metabol Drug Interact. 1994;11(4):341-57. doi: 10.1515/dmdi.1994.11.4.341.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: August 29, 2012
• First Submitted That Met QC Criteria: August 30, 2012
• First Posted (Estimate): August 31, 2012

Study Record Updates

• Last Update Posted (Estimate): August 31, 2012
• Last Update Submitted That Met QC Criteria: August 30, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; bioavailability; bioequivalence; glimepiride; sulphonylurea; anti-hyperglycaemic
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Glimepiride
• Other Study ID Numbers: BE-Glimepiride