Bioequivalence Study of 4 mg Glimepiride Tablet

• ClinicalTrials.gov Identifier: NCT01677247
• Recruitment Status: Completed
• First Posted: August 31, 2012
• Last Update Posted: August 31, 2012
• Sponsor: Dexa Medica Group
• Information provided by (Responsible Party): Dexa Medica Group

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Glimepiride BE Study in Healthy Volunteers Under Fasting Condition	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	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Bioequivalence Study of Two Formulations of Glimepiride Tablet in Healthy Subjects
• Study Start Date: February 2011
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: March 2011

Arms and Interventions

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 Name: Amaryl®, manufactured by PT Sanofi Aventis

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Indonesia

PT Equilab International

Jakarta, Indonesia, 12430

Sponsors and Collaborators

Dexa Medica Group

Investigators

• Principal Investigator: Danang A. Yunaidi, MD; PT. Equilab International

More Information

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.

• Responsible Party: Dexa Medica Group
• ClinicalTrials.gov Identifier: NCT01677247
• Other Study ID Numbers: BE-Glimepiride
• First Posted: August 31, 2012
• Last Update Posted: August 31, 2012
• Last Verified: August 2012

Keywords provided by Dexa Medica Group:

sulphonylurea; anti-hyperglycaemic; bioavailability; bioequivalence; glimepiride; pharmacokinetics

Additional relevant MeSH terms:

Glimepiride; Anti-Arrhythmia Agents; Hypoglycemic Agents; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors