Fasting Study of Metolazone Tablets 10 mg and Zaroloxyn® Tablets 10 mg

• ClinicalTrials.gov Identifier: NCT00650195
• Recruitment Status: Completed
• First Posted: April 1, 2008
• Last Update Posted: April 1, 2008
• Sponsor: Mylan Pharmaceuticals Inc
• Information provided by: MylanPharma

Study Description

Brief Summary:

The objective of this study was to investigate the bioequivalence of Mylan metolazone 10 mg tablets to Celltech Zaroxolyn® 10 mg tablets following a single, oral 10 mg (1 x 10 mg) dose administration under fasting conditions.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Metolazone Tablets 10 mg; Drug: Zaroloxyn® Tablets 10 mg	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: Single-Dose Fasting In Vivo Bioequivalence Study of Metolazone Tablets (10 mg; Mylan) and Zaroloxyn® Tablets (10 mg; Celltech) in Healthy Volunteers
• Study Start Date: February 2004
• Actual Primary Completion Date: February 2004
• Actual Study Completion Date: March 2004

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Metolazone Tablets 10 mg	Drug: Metolazone Tablets 10 mg; 10mg, single dose fasting
Active Comparator: 2; Zaroloxyn® Tablets 10 mg	Drug: Zaroloxyn® Tablets 10 mg; 10mg, single dose fasting

Outcome Measures

Primary Outcome Measures :

1. Bioequivalence [ Time Frame: within 30 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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 b-human chorionic gonadotropin (β-HCG) pregnancy tests performed within 14 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 samples for β-HCG testing may be collected and sent for analysis within 48 hours prior to dosing for both study periods. An additional serum (Beta-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. No hormonal contraceptives or hormonal replacement therapy 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 sterility (tubal ligation, oophorectomy or hysterectomy) or postmenopausal accompanied with a documented postmenopausal course of at least one year.
   3. During the course of the study, from study screen until study exit - including the washout period, women of childbearing potential must use a spermicide containing barrier method of contraception in addition to their current contraceptive device. 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 7 days 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 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.
   3. Use of hormonal contraceptives and hormonal replacement therapy within three months prior to the initial dose of study medication.

4. Diseases:

   1. History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic disease.
   2. History of drug and/or alcohol abuse within 1 year prior to the study.
   3. Acute illness at the time of either the pre-study medical evaluation or dosing.

5. Abnormal and clinically significant laboratory test results:

   1. Any laboratory result deemed a clinically significant deviation by the investigator.
   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 7 days of drug administration.

Contacts and Locations

Locations

United States, West Virginia

Kendle International Inc.

Morgantown, West Virginia, United States, 26505

Sponsors and Collaborators

Mylan Pharmaceuticals Inc

Investigators

• Principal Investigator: Dorian Williams, M.D.; Kendle International Inc.

More Information

Additional Information:

Mylan Pharmaceuticals Inc. - Clinical Trial Results 

Daily Med - posting of most recent submitted labelling to the Food and Drug Administration (FDA) and currently in use 

Recalls, Market Withdrawals and Safety Alerts 

• Responsible Party: Will Sullvan, Global Head of Product Risk and Safety Management, Mylan Inc.
• ClinicalTrials.gov Identifier: NCT00650195
• Other Study ID Numbers: METO-0409
• First Posted: April 1, 2008
• Last Update Posted: April 1, 2008
• Last Verified: March 2008

Additional relevant MeSH terms:

Metolazone; Antihypertensive Agents; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action