Losartan 100 mg Tablets in Healthy Subjects Under Fasting Conditions

Randomized, 2-way Crossover, Bioequivalence Study of Losartan 100 mg Tablets and Cozaar® Administered as 1 * 100 mg Tablet in Healthy Subjects Under Fasting Conditions

The objective of this study is to compare the rate and extent of absorption of losartan 100 mg tablets (test) versus Cozaar® (reference), administered as 1 * 100 mg tablet under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Losartan; Drug: Cozaar®

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA Bioequivalence Statistical Methods

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3X 2H9
      • Anapharm Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Non-child-bearing potential female or male.
• Non-smoker.
• 18 years of age and older.
• Capable of consent.

• Non-child-bearing potential female subject:

  • Post-menopausal state: absence of menses for 12 months prior to drug administration.
  • Surgically sterile: hysterectomy, bilateral oophorectomy, or tubal ligation at least 6 months prior to drug administration.

Exclusion Criteria:

• Clinically significant illness within 4 weeks prior to the administration of the study medication.
• Clinically significant surgery within 4 weeks prior to the administration of the study medication.
• Any clinically significant abnormality found during medical screening.
• Any reason which, in the opinion of the Medical Sub-Investigator, would prevent the subject from participating in the study.
• Abnormal laboratory tests judged clinically significant.
• Positive urine drug screen at screening.
• Positive testing for hepatitis B, hepatitis C, or HIV at screening.
• ECG abnormalities (clinically significant) or vital sign abnormalities (systolic blood pressure lower than 100 or over 140 mmHg, diastolic blood pressure lower than 60 or over 100 bpm) at screening.
• Subjects with BMI > 30.0.
• History of significant alcohol abuse within 6 months prior to screening visit or any indication of the regular use of more than 14 units of alcohol per week (1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol).
• History of drug abuse or use of illegal drugs: use of soft drugs (such as marijuana) within 3 months prior to screening visit or hard drugs (such as cocaine, phencyclidine [PCP], and crack) within 1 year prior to the screening visit.
• History of allergic reactions to losartan or other related drugs.
• History of allergic reactions to heparin.
• Use of any drugs known to induce or inhibit drug metabolism within 30 days prior to administration of the study medication.
• Use of an investigational drug or participation in an investigational study within 30 days prior to administration of the study medication.
• Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowl diseases), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the study drug.
• Any clinically significant history or presence of clinically significant neurological, endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric, or metabolic disease.
• Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products (including natural food supplements, vitamins, garlic as a supplement) within 7 days prior to administration of study medication, except for topical products without systemic absorption.
• Positive alcohol breath test at screening.
• Subjects who have used tobacco in any form within 90 days preceding study drug administration.
• Any food allergy, intolerance, restriction, or special diet that could, in the opinion of the Medical Sub-Investigator, contraindicate the subjects participation in this study.
• A dept injection or an implant of any drug within 3 months prior to administration of study medication.

• Donation of plasma (500 mL) within 7 days prior to drug administration. Donation or loss of whole blood prior to administration of the study medication as follows:

  • Less than 300 mL of whole blood within 30 days
  • 300 mL to 500 mL of whole blood within 45 days, or
  • more than 500 mL of whole blood within 56 days prior to drug administration.
• Consumption of food or beverages containing grapefruit (e.g. fresh, canned, or frozen) within 7 days prior to administration of the study medication.
• Clinically significant history of known active hypotension or volume depletion.
• Intolerance to venipuncture.
• Clinically significant history of renal, hepatic, or cardiovascular disease, tuberculosis, epilepsy, asthma, diabetes, psychosis, or glaucoma will not be eligible for this study.
• Subjects unable to understand or unwilling to sign the Informed Consent Form.

• Additional exclusion criteria for females only;

  • Breast-feeding subjects.
  • Positive urine pregnancy test at screening (performed for all females).

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Reference Listed Drug; Cozaar® 100 mg Tablets	Drug: Cozaar®; 100 mg Tablet; Other Names: Losartan (generic name)
Experimental: Generic Test Product; Losartan 100mg Tablets	Drug: Losartan; 100 mg Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Losartan (Maximum Observed Concentration of Drug Substance in Plasma)	Bioequivalence based on Losartan Cmax.	Blood samples collected over a 24 hour period.
AUC0-t of Losartan (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)	Bioequivalence based on Losartan AUC0-t.	Blood samples collected over a 24 hour period.
AUC0-inf of Losartan (Area Under the Concentration-time Curve From Time Zero to Infinity)	Bioequivalence based on Losartan AUC0-inf.	Blood samples collected over a 24 hour period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Losartan Carboxy Acid (Maximum Observed Concentration of Drug Substance in Plasma)	Informational comparison of Cmax values for the metabolite Losartan Carboxy Acid.	Blood samples collected over a 24 hour period.
AUC0-t of Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)	Informational comparison of AUC0-t values for the metabolite Losartan Carboxy Acid.	Blood samples collected over a 24 hour period.
AUC0-inf of Losartan Carboxy Acid(Area Under the Concentration-time Curve From Time Zero to Infinity)	Informational comparison of AUC0-inf values for the metabolite Losaran Carboxy Acid.	Blood samples collected over a 24 hour period.

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA
• Investigators: Principal Investigator: Richard Larouche, MD, Anapharm

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): November 1, 2003
• Study Completion (Actual): November 1, 2003

Study Registration Dates

• First Submitted: May 13, 2010
• First Submitted That Met QC Criteria: May 13, 2010
• First Posted (Estimate): May 14, 2010

Study Record Updates

• Last Update Posted (Estimate): December 8, 2010
• Last Update Submitted That Met QC Criteria: November 22, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 30272