Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
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.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 5 mg/500 mg, single-dose fasting
1 x 5 mg/500 mg, single-dose fasting
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration) - Glipizide in Plasma | Blood samples collected over 36 hour period | Bioequivalence based on Cmax |
| 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 |
| 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 |
| Cmax (Maximum Observed Concentration) - Metformin in Plasma | Blood samples collected over 36 hour period | Bioequivalence based on Cmax |
| 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 |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glipizide Metformin (Test) First Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in first period followed by Metaglip® 5/500 mg Tablet (reference) dosed in second period | 20 |
| Metaglip® (Reference) First Metaglip® 5/500 mg Tablet (reference) dosed in first period followed by Glipizide Metformin Hydrochloride 5/500 mg Tablet (test) dosed in second period | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | Glipizide Metformin (Test) First | Metaglip® (Reference) First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 20 Participants | 20 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 36 Participants | 16 Participants | 20 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 40 participants | 20 participants | 20 participants |
| Sex: Female, Male Female | 13 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 27 Participants | 17 Participants | 10 Participants |
Outcome results
Primary
AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)]- Glipizide
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide Metformin | AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)]- Glipizide | 2032.8 ng*h/mL | Standard Deviation 655.53 |
| Metaglip® | AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)]- Glipizide | 2092.9 ng*h/mL | Standard Deviation 684.16 |
90% CI: [94.2, 99.9]
Primary
AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Metformin
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide Metformin | AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Metformin | 3912.0 ng*h/mL | Standard Deviation 738.53 |
| Metaglip® | AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Metformin | 4212.7 ng*h/mL | Standard Deviation 787.61 |
90% CI: [88.4, 97.1]
Primary
AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Glipizide
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide Metformin | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Glipizide | 2005.8 ng*h/mL | Standard Deviation 638.5 |
| Metaglip® | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Glipizide | 2065.1 ng*h/mL | Standard Deviation 667.92 |
90% CI: [94.2, 99.8]
Primary
AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)]- Metformin
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide Metformin | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)]- Metformin | 3701.3 ng*h/mL | Standard Deviation 712 |
| Metaglip® | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)]- Metformin | 3979.2 ng*h/mL | Standard Deviation 793.07 |
90% CI: [88.8, 97.5]
Primary
Cmax (Maximum Observed Concentration) - Glipizide in Plasma
Bioequivalence based on Cmax
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide Metformin | Cmax (Maximum Observed Concentration) - Glipizide in Plasma | 337.100 ng/mL | Standard Deviation 69.6511 |
| Metaglip® | Cmax (Maximum Observed Concentration) - Glipizide in Plasma | 392.150 ng/mL | Standard Deviation 94.7365 |
90% CI: [81.8, 91.6]
Primary
Cmax (Maximum Observed Concentration) - Metformin in Plasma
Bioequivalence based on Cmax
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide Metformin | Cmax (Maximum Observed Concentration) - Metformin in Plasma | 640.00 ng/mL | Standard Deviation 120.249 |
| Metaglip® | Cmax (Maximum Observed Concentration) - Metformin in Plasma | 724.98 ng/mL | Standard Deviation 172.939 |
90% CI: [83.5, 94.6]