Clinical trial NCT00649051: Fasting Study of Metolazone Tablets 2.5 mg and Zaroloxyn® Tablets 2.5 mg
Official title: Single-Dose Fasting In Vivo Bioequivalence Study of Metolazone Tablets (2.5 mg; Mylan) and Zaroloxyn® Tablets (2.5 mg; Celltech) in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Viatris Inc.
Sponsor class: INDUSTRY
First posted: 2008-04-01
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Bioequivalence
timeFrame: within 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Charles
country: United States
facility: Gateway Medical Research, Inc.
state: Missouri
Study officials:
affiliation: Cetero Research, San Antonio
name: Thomas Siler, M.D.
role: PRINCIPAL_INVESTIGATOR
References: