Glimepiride 4 mg Tablets Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834340
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Duration (Days): 28
• Patients Per Site Per Month: 34.8

Study Details

Study Description

Brief Summary

The objective of this study is to compare the relative bioavailability of glimepiride 4 mg tablets (manufactured by TEVA Pharmaceutical Industries, Ltd. and distributed by TEVA Pharmaceuticals USA) with that of AMARYL® tablets (Aventis) in healthy, adult, non-smoking subjects under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Glimepiride 4 mg Tablets; Drug: AMARYL® 4 mg Tablets	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of Glimepiride 4 mg Tablets Under Fasting Conditions
• Study Start Date: Feb 1, 2003
• Actual Primary Completion Date: Mar 1, 2003
• Actual Study Completion Date: Mar 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glimepiride Glimepiride 4 mg Tablet (test) dosed in first period followed by Amaryl® 4 mg Tablet (reference) dosed in second period	Drug: Glimepiride 4 mg Tablets; 1 x 4 mg, single-dose fasting
Active Comparator: Amaryl® Amaryl® 4 mg Tablet (reference) dosed in first period followed by Glimepiride 4 mg Tablet (test) dosed in second period	Drug: AMARYL® 4 mg Tablets; 1 x 4 mg, single-dose fasting

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [Blood samples collected over 24 hour period]

   Bioequivalence based on Cmax

2. AUCinf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) [Blood samples collected over 24 hour period]

   Bioequivalence based on AUCinf

3. AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration [Blood samples collected over 24 hour period]

   Bioequivalence based on AUC0-t

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• All subjects selected for this study will be non-smokers at least 18 years of age. Subjects will have a BMI (body mass index) of 30 or less.

• Each subject shall be given a general physical examination within 28 days of initiation of the study. Such examination includes, but is not limited to, blood pressure, general observations, and history.

Each female subject will be given a serum pregnancy test as part of the pre-study screening process.

Adequate blood and urine samples should be obtained within 28 days before beginning of the first period and at the end of the trial for clinical laboratory measurements.

Clinical laboratory measurements will include the following:

• Hematology: hemoglobin, hematocrit, red blood cell count, platelets, whit blood cell count (with differential).

• Clinical Chemistry: creatinine, BUN, glucose, SGOT/AST, SGPT/ALT, bilirubin, and alkaline phosphatase.

• Urine Analysis: pH, specific gravity, protein, glucose, ketones, bilirubin, occult blood, and cells.

• HIV Screen: pre-study only.

• Hepatitis-B, C Screen: pre-study only.

• Drugs of Abuse Screen: pre-study and at each check-in. Subjects will be selected if all above are normal.

Exclusion Criteria:

• Subjects with a significant recent history of chronic alcohol consumption, drug addiction, or serious gastrointestinal, renal, hepatic or cardiovascular disease, tuberculosis, epilepsy, asthma, diabetes, psychosis or glaucoma will not be eligible for this study.

• Subjects whose clinical laboratory test values are greater than 20% outside the normal range may be retested. If the clinical values are outside the range on retesting, the subject will not be eligible to participate in the study unless the clinical investigator deems the result to not be significant.

• Subjects who have a history of allergic responses to the class of drug being tested will be excluded from the study.

• Subjects who use tobacco in any form will not be eligible to participate in the study. Three months abstinence is required.

• All subjects will have urine samples assayed for the presence of drugs of abuse as part of the clinical laboratory screening procedures and at each dosing period check-in. Subjects found to have urine concentrations of any of the tested drugs will not be allowed to participate.

• Subjects should not have donated blood and/or plasma for at least thirty (30) days prior to the first dosing of the study.

• Subjects who have taken any investigational drug within thirty (30) days prior to the first dosing of the study will not be allowed to participate.

• Female subjects who are pregnant, breast-feeding, or who are likely to become pregnant during the study will not be allowed to participate. Female subjects of childbearing potential must either abstain from sexual intercourse or use a reliable barrier method (e.g. condom, IUD) of contraception during the course of the study (first dosing until last blood collection) or they will not be allowed to participate. Female subjects who have used hormonal oral contraceptives within 14 days of dosing or implanted or injected hormonal contraceptives within 180 days of dosing will not be allowed to participate.

• All female subjects will be screened for pregnancy at check-in each study period. Subjects with positive or inconclusive results will be withdrawn from the study.

• Subjects who do not tolerate venipuncture will not be allowed to participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novum Pharmaceutical Research Services	Houston	Texas	United States	77042

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Solomon G. Ghide, M.D., Novum Pharmaceutical Research Services

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00834340
• Other Study ID Numbers: B036501
• First Posted: Feb 3, 2009
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Glimepiride

Study Results

Participant Flow

Arm/Group Title	Glimepiride (Test) First	Amaryl® (Reference) First
Arm/Group Description	Glimepiride 4 mg Tablet (test) dosed in first period followed by Amaryl® 4 mg Tablet (reference) dosed in second period	Amaryl® 4 mg Tablet (reference) dosed in first period followed by Glimepiride 4 mg Tablet (test) dosed in second period
Period Title: First Intervention
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	16	16
COMPLETED	14	16
NOT COMPLETED	2	0
Period Title: First Intervention
STARTED	14	16
COMPLETED	14	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Glimepiride (Test) First	Amaryl® (Reference) First	Total
Arm/Group Description	Glimepiride 4 mg Tablet (test) dosed in first period followed by Amaryl® 4 mg Tablet (reference) dosed in second period	Amaryl® 4 mg Tablet (reference) dosed in first period followed by Glimepiride 4 mg Tablet (test) dosed in second period	Total of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	16 100%	32 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 25%	5 31.3%	9 28.1%
Male	12 75%	11 68.8%	23 71.9%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	3 18.8%	0 0%	3 9.4%
Black	4 25%	8 50%	12 37.5%
Hispanic	8 50%	8 50%	16 50%
Biracial	1 6.3%	0 0%	1 3.1%
Region of Enrollment (participants) [Number]
United States	16 100%	16 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 24 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Glimepiride	Amaryl®
Arm/Group Description	Glimepiride 4 mg Tablet (test) dosed in either period	Amaryl® 4 mg Tablet (reference) dosed in either period
Measure Participants	30	30
Mean (Standard Deviation) [ng/mL]	231.700 (97.290)	226.890 (88.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glimepiride, Amaryl®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	101
	Confidence Interval	() 90%; 92.2 to 111
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

2. Primary Outcome

Title	AUCinf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Description	Bioequivalence based on AUCinf
Time Frame	Blood samples collected over 24 hour period

Outcome Measure Data

Analysis Population Description

The parameter of AUCinf could not be estimated for one subject.

Arm/Group Title	Glimepiride	Amaryl®
Arm/Group Description	Glimepiride 4 mg Tablet (test) dosed in either period	Amaryl® 4 mg Tablet (reference) dosed in either period
Measure Participants	29	29
Mean (Standard Deviation) [ng*h/mL]	1613.846 (553.310)	1660.082 (637.392)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glimepiride, Amaryl®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	98.5
	Confidence Interval	() 90%; 94.0 to 103
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

3. Primary Outcome

Title	AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 24 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Glimepiride	Amaryl®
Arm/Group Description	Glimepiride 4 mg Tablet (test) dosed in either period	Amaryl® 4 mg Tablet (reference) dosed in either period
Measure Participants	30	30
Mean (Standard Deviation) [ng*h/mL]	1479.961 (524.507)	1469.352 (548.723)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glimepiride, Amaryl®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	102
	Confidence Interval	() 90%; 98.7 to 105
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principal Investigator is not permitted to discuss or publish trial results.