The objective of this study was to investigate the bioequivalence of Mylan metolazone 2. 5 mg
tablets to Celltech Zaroxolyn® 2. 5 mg tablets following a single, oral 10 mg (4 x 2. 5 mg)
dose administration under fasting conditions.
Inclusion Criteria:
1. Age: 18 years and older
2. Sex: Male and/or non-pregnant, non-lactating female
1. Women of childbearing potential must have negative serum (β-HCG) pregnancy tests
performed within 14 days prior to the start of the study and within 72 hours
prior to the start of dosing for each treatment period. An additional serum
(β-HCG) pregnancy test will be performed upon completion of the study.
2. Women of childbearing potential must practice abstinence or use an acceptable
form of contraception throughout the duration of the 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 sterility (tubal ligation, oophorectomy or hysterectomy) or
postmenopausal accompanied with a postmenopausal course of at least one
year, as documented on the subject's medical history.
3. During the course of the study, from study screen until study exit - including
the washout period, males must use a spermicide-containing barrier method of
contraception to prevent the pregnancy of their sexual partner. This advice
should be documented in the informed consent form.
3. Weight: At least 60 kg (132 lbs.) for men and 48 kg (106 lbs.) for women and 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, 12-lead ECG, Hepatitis B, Hepatitis C
and HIV tests, and urine drug screen including amphetamine, benzodiazepine,
cannabinoid, cocaine, opiate screen, and phencyclidine) performed within 14 days of
the initial dose of study medication.
Exclusion Criteria:
1. Institutionalized subjects will not be used.
2. Social Habits:
1. Use of any tobacco products within one year prior to dosing.
2. Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage
within the 48 hours prior to the initial dose of study medication.
3. Ingestion of any vitamins or herbal products within the 48 hours prior to the
initial dose of the study medication.
4. Any recent, significant change in dietary or exercise habits.
3. Medications:
1. Use of any medication within the last 14 days prior to the initial dose of study
medication, including the use of oral contraceptives, hormone replacement
therapy, and over-the-counter medications.
2. Use of any medication known to alter hepatic enzyme activity within 28 days prior
to the initial dose of study medication.
4. Diseases:
1. History of any significant chronic disease and/or hepatitis.
2. History of drug and/or alcohol abuse.
3. Acute illness at the time of either the pre-study medical evaluation or dosing.
4. A positive HIV, Hepatitis B, or Hepatitis C test result.
5. Abnormal and clinically significant laboratory test results:
1. Clinically significant deviation from the Guide to Clinically Relevant
Abnormalities (See Part II ADMINISTRATIVE ASPECTS OF BIOEQUIVALENCE PROTOCOLS).
2. 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 metolazone, sulfonamide-derived drugs, thiazides,
quinethazone or other 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 48 hours of drug
administration.
