The objective of this study was to investigate the bioequivalence of Mylan's glipizide and
metformin HCl 5 mg/500 mg tablets to Bristol-Myers Squibb's Metaglip® 5 mg/500 mg tablets
following a single, oral 5 mg/500 mg (1 x 5 mg/500 mg) dose administration under fed
1. Age: 18 years and older
2. Sex: Male and/or non-pregnant, non-lactating female a. Women of childbearing
potential must have a negative serum (β‑HCG) pregnancy test performed within 21 days
prior to the start of the study and on the evening prior to each dose administration.
If dosing is scheduled on Sunday or Monday, serum may be collected for the HCG
pregnancy test within 48 hours prior to dosing for each study period. An additional
serum (β‑HCG) pregnancy test will be performed upon completion of the study. b. Women
must practice abstinence or use an acceptable form of contraception throughout the
duration of the study. No hormonal contraceptives or hormonal replacement therapies
are permitted in this study. Acceptable forms of contraception include the
following: 1) intrauterine device in place for at least 3 months prior to the start
of the study and remaining in place during the study period, or 2) barrier methods
containing or used in conjunction with a spermicidal agent, or 3) surgical
sterilization c. Women will not be considered of childbearing potential if one of the
following is reported and documented on the medical history: 1) postmenopausal with
an absence of menses for at least one (1) year, or 2) bilateral oophorectomy with or
without a hysterectomy and an absence of bleeding for at least 6 months, or 3) total
hysterectomy d. During the course of the study, from study screen until study exit -
including the washout period, all men and women of childbearing potential must use a
spermicide containing barrier method of contraception in addition to their current
contraceptive method. This advice should be documented in the informed consent form.
3. At least 60 kg (132 lbs.) for men and 48 kg (106 lbs.) for women and all subjects
within 15% of Ideal Body Weight (IBW), as referenced by the Table of "Desirable
Weights of Adults" Metropolitan Life Insurance Company, 1999 (See Part II
ADMINISTRATIVE ASPECTS OF BIOEQUIVALENCE PROTOCOLS).
4. All subjects should be judged normal and healthy during a pre-study medical
evaluation (physical examination, laboratory evaluation, hepatitis B and hepatitis C
tests, HIV test, 12-lead ECG, and urine drug screen including amphetamine,
barbiturates, benzodiazepines, cannabinoid, cocaine, opiate screen, phencyclidine,
and methadone) performed within 21 days of the initial dose of study medication.
1. Institutionalized subjects will not be used.
2. Social Habits: a. Use of any tobacco products within 1 year prior to dosing. b.
Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within
the 48 hours prior to the initial dose of study medication. c. Ingestion of any
vitamins or herbal products within 7 days prior to the initial dose of the study
medication. d. Any recent, significant change in dietary or exercise habits. e. A
positive test for any drug included in the urine drug screen. f. History of drug
and/or alcohol abuse.
3. Medications: a. Use of any prescription or over-the-counter (OTC) medications within
the 14 days prior to the initial dose of study medication. b. Use of any hormonal
contraceptives or hormone replacement therapy within 3 months prior to study
medication dosing. c.Use of any medication known to alter hepatic enzyme activity
within 28 days prior to the initial dose of study medication.
4. Diseases: a. History of any significant cardiovascular, hepatic, renal, pulmonary,
hematologic, gastrointestinal, endocrine, immunologic, dermatologic, or neurologic
disease. b. Acute illness at the time of either the pre-study medical evaluation or
dosing. c. A positive HIV, hepatitis B, or hepatitis C test. d. Renal disease or
renal dysfunction (as suggested by serum creatinine levels ³ 1.5 mg/dL (for males)
and ³ 1.4 mg/dL (for females) or abnormal creatinine clearance).
5. Abnormal and clinically significant laboratory test results: a. Clinically
significant deviation from the Guide to Clinically Relevant Abnormalities (See Part
II ADMINISTRATIVE ASPECTS OF BIOEQUIVALENCE PROTOCOLS). b. Abnormal and clinically
relevant ECG tracing.
6. Donation or loss of a significant volume of blood or plasma (> 450 mL) within 28 days
prior to the initial dose of study medication.
7. Subjects who have received an investigational drug within 30 days prior to the
initial dose of study medication.
8. Allergy or hypersensitivity to metformin hydrochloride, glipizide, sulfonylureas or
any related products.
9. History of difficulties in swallowing, or any gastrointestinal disease which could
affect the drug absorption.
10. Consumption of grapefruit or grapefruit containing products within 7 days of drug