5 mg Glipizide/500 mg Metformin Hydrochloride Tablets, Fasting

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00835497
• Collaborator: (none)
• Enrollment: 40
• Locations: 2
• Arms: 2
• Patients Per Site: 20

Study Details

Study Description

Brief Summary

This study will compare the relative bioavailability (rate and extent of absorption) of 5 mg Glipizide/500 mg Metformin Hydrochloride Tablets manufactured by TEVA Pharmaceutical Industries, Ltd., and distributed by TEVA Pharmaceuticals USA with that of 5 mg/500 mg METAGLIP™ Tablets by Bristol-Myers Squibb Company following a single oral dose (1 x 5 mg/500 mg tablet) in healthy adult subjects administered under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: 5 mg/500 mg Glipizide Metformin Hydrochloride Tablets; Drug: 5 mg/500 mg METAGLIP™ Tablets	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of 5 mg Glipizide/500 mg Metformin Hydrochloride Tablets Under Fasting Conditions.
• Study Start Date: Jun 1, 2004
• Actual Primary Completion Date: Jun 1, 2004
• Actual Study Completion Date: Jun 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glipizide Metformin Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in first period followed by Metaglip® 5/500 mg Tablet (reference) dosed in second period	Drug: 5 mg/500 mg Glipizide Metformin Hydrochloride Tablets; 1 x 5 mg/500 mg, single-dose fasting
Active Comparator: Metaglip® Metaglip® 5/500 mg Tablet (reference) dosed in first period followed by Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in second period	Drug: 5 mg/500 mg METAGLIP™ Tablets; 1 x 5 mg/500 mg, single-dose fasting

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration) - Glipizide in Plasma [Blood samples collected over 36 hour period]

   Bioequivalence based on Cmax

2. AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)]- Glipizide [Blood samples collected over 36 hour period]

   Bioequivalence based on AUC0-inf

3. AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Glipizide [Blood samples collected over 36 hour period]

   Bioequivalence based on AUC0-t

4. Cmax (Maximum Observed Concentration) - Metformin in Plasma [Blood samples collected over 36 hour period]

   Bioequivalence based on Cmax

5. AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Metformin [Blood samples collected over 36 hour period]

   Bioequivalence based on AUC0-inf

6. AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)]- Metformin [Blood samples collected over 36 hour period]

   Bioequivalence based on AUC0-t

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Screening Demographics: All subjects selected for this study will be healthy men and women 18-45 years of age, inclusive, at the time of dosing. The subject's body mass index (BMI) should be less than or equal to 30.

• Screening Procedures: Each subject will complete the screening process within 28 days prior to Period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures.

Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature. The physical examination will include, but may not be limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems.

The screening clinical laboratory procedures will include:

• Hematology: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet count;

• Clinical Chemistry: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase;

• HIV antibody, hepatitis B surface antigen, and hepatitis C antibody screens;

• Urinalysis: by dipstick; full microscopic examination if dipstick positive; and

• Urine Drug Screen: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates, and phencyclidine.

• Serum Pregnancy Screen

If female and:

• of childbearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condom with spermicide, diaphragm with spermicide, intrauterine device (IUD), or abstinence; or

• is postmenopausal for at least 1 year; or

• is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).

Exclusion Criteria:

• Subjects with a recent history of drug or alcohol addiction or abuse.

• Subjects with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators).

• Subjects whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant.

• Subjects demonstrating a reactive hepatitis B surface antigen screen, a reactive hepatitis C antibody screen, or a reactive HIV antibody screen.

• Subjects demonstrating a positive drug abuse screen when screened for this study.

• Female subjects demonstrating a positive pregnancy screen.

• Female subjects who are currently breastfeeding.

• Subjects with a history of allergic response(s) to glipizide, metformin hydrochloride, or related drugs.

• Subjects with a history of clinically significant allergies including drug allergies.

• Subjects with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators).

• Subjects who currently use or report using tobacco products within 90 days of Period I dose administration.

• Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing.

• Subjects who report donating greater than 150 mL of blood within 28 days prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study.

• Subjects who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for four weeks after completing the study.

• Subjects who report receiving any investigational drug within 28 days prior to Period I dosing.

• Subjects who report taking any systemic prescription medication in the 14 days prior to Period I dosing.

• Subjects who report an intolerance of direct venipuncture.

• Subjects who report consuming an abnormal diet during the 28 days prior to Period I dosing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRACS Institute Ltd.	East Grand Forks	Minnesota	United States	56721
2	PRACS Institute, Ltd.	Fargo	North Dakota	United States	58104

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: James D. Carlson, Pharm.D., PRACS Institute, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00835497
• Other Study ID Numbers: R04-0476
• First Posted: Feb 3, 2009
• Last Update Posted: Sep 15, 2009
• Last Verified: Sep 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Glipizide Metformin (Test) First	Metaglip® (Reference) First
Arm/Group Description	Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in first period followed by Metaglip® 5/500 mg Tablet (reference) dosed in second period	Metaglip® 5/500 mg Tablet (reference) dosed in first period followed by Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in second period
Period Title: First Intervention
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Glipizide Metformin (Test) First	Metaglip® (Reference) First	Total
Arm/Group Description	Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in first period followed by Metaglip® 5/500 mg Tablet (reference) dosed in second period	Metaglip® 5/500 mg Tablet (reference) dosed in first period followed by Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in second period	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 15%	10 50%	13 32.5%
Male	17 85%	10 50%	27 67.5%
Race/Ethnicity, Customized (Number) [Number]
Native American	1 5%	0 0%	1 2.5%
Caucasian	16 80%	20 100%	36 90%
Asian	2 10%	0 0%	2 5%
Hispanic	1 5%	0 0%	1 2.5%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Concentration) - Glipizide in Plasma
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 36 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	Glipizide Metformin	Metaglip®
Arm/Group Description	Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in either period	Metaglip® 5/500 mg Tablet (reference) dosed in either period
Measure Participants	40	40
Mean (Standard Deviation) [ng/mL]	337.100 (69.6511)	392.150 (94.7365)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide Metformin, Metaglip®
	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	Test/Ref Ratio of LS Means x 100
	Estimated Value	86.5
	Confidence Interval	() 90%; 81.8 to 91.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

2. Primary Outcome

Title	AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)]- Glipizide
Description	Bioequivalence based on AUC0-inf
Time Frame	Blood samples collected over 36 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	Glipizide Metformin	Metaglip®
Arm/Group Description	Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in either period	Metaglip® 5/500 mg Tablet (reference) dosed in either period
Measure Participants	40	40
Mean (Standard Deviation) [ng*h/mL]	2032.8 (655.53)	2092.9 (684.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide Metformin, Metaglip®
	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	Test/Ref Ratio of LS Means x 100
	Estimated Value	97.0
	Confidence Interval	() 90%; 94.2 to 99.9
	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 (Per Participant)] - Glipizide
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 36 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	Glipizide Metformin	Metaglip®
Arm/Group Description	Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in either period	Metaglip® 5/500 mg Tablet (reference) dosed in either period
Measure Participants	40	40
Mean (Standard Deviation) [ng*h/mL]	2005.8 (638.50)	2065.1 (667.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide Metformin, Metaglip®
	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	Test/Ref Ratio of LS Means x 100
	Estimated Value	97.0
	Confidence Interval	() 90%; 94.2 to 99.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

4. Primary Outcome

Title	Cmax (Maximum Observed Concentration) - Metformin in Plasma
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 36 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	Glipizide Metformin	Metaglip®
Arm/Group Description	Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in either period	Metaglip® 5/500 mg Tablet (reference) dosed in either period
Measure Participants	40	40
Mean (Standard Deviation) [ng/mL]	640.00 (120.249)	724.98 (172.939)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide Metformin, Metaglip®
	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	Test/Ref Ratio of LS Means x 100
	Estimated Value	88.9
	Confidence Interval	() 90%; 83.5 to 94.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

5. Primary Outcome

Title	AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Metformin
Description	Bioequivalence based on AUC0-inf
Time Frame	Blood samples collected over 36 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	Glipizide Metformin	Metaglip®
Arm/Group Description	Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in either period	Metaglip® 5/500 mg Tablet (reference) dosed in either period
Measure Participants	40	40
Mean (Standard Deviation) [ng*h/mL]	3912.0 (738.53)	4212.7 (787.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide Metformin, Metaglip®
	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	Test/Ref Ratio of LS Means x 100
	Estimated Value	92.7
	Confidence Interval	() 90%; 88.4 to 97.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

6. Primary Outcome

Title	AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)]- Metformin
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 36 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	Glipizide Metformin	Metaglip®
Arm/Group Description	Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in either period	Metaglip® 5/500 mg Tablet (reference) dosed in either period
Measure Participants	40	40
Mean (Standard Deviation) [ng*h/mL]	3701.3 (712.00)	3979.2 (793.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glipizide Metformin, Metaglip®
	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	Test/Ref Ratio of LS Means x 100
	Estimated Value	93.0
	Confidence Interval	() 90%; 88.8 to 97.5
	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.