Losartan Potassium/Hydrochlorothiazide 100/25 mg Tablets in Healthy Subjects Under Fasting Conditions

A Relative Bioavailability Study of 100/25 mg Losartan Potassium/Hydrochlorothiazide Tablets Under Fasting Conditions

The object of this study was to compare the relative bioavailability (rate and extent of absorption) of 100/25 mg Losartan potassium/Hydrochlorothiazide Tablets manufactured by Teva Pharmaceutical Industries Ltd. and distributed by Teva Pharmaceuticals USA with that of Hyzaar® 100/25 mg Tablets distributed by Merck & Co., Inc. following a single oral dose (1 x 100/25 mg tablet) in healthy adult subjects administered under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Losartan potassium/Hydrochlorothiazide; Drug: Hyzaar®

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA Bioequivalence Statistical Methods

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • PRACS Institute, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men and women, 18-45 years of age (inclusive).
• Body mass index should be less than or equal to 30
• Screening procedures completed within 28 days prior to dosing.

• If female and:

  • of child bearing potential, is practicing an acceptable barrier method of birth control for the duration of the study
  • is postmenopausal for at least 1 year
  • is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy)

Exclusion Criteria:

• Subjects with a recent history of drug or alcohol abuse or addiction.
• Subjects with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators).
• Subjects whose clinical laboratory test values the accepted reference range and when confirmed on re-examination are deemed to be clinically significant.
• Subjects demonstrating a positive hepatitis B surface antigen screen, a positive hepatitis C antibody screen, or a reactive HIV antibody screen.
• Subjects demonstrating a positive drug abuse screen when screened for the study.
• Female subjects demonstrating a positive pregnancy screen.
• Female subjects who are currently breastfeeding.
• Subjects who have used implanted or injected hormonal contraceptives anytime during the 180 days prior to study dosing or hormonal contraceptives within 14 days of dosing will not be allowed to participate.
• Subjects with a history of allergic response(s) to losartan, hydrochlorothiazide or related drugs.
• Subjects with a history of clinically significant allergies including drug allergies.
• Subjects with a clinically significant illness during the 4 weeks prior to dosing (as determined by the clinical investigators).
• Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to dosing.
• Subjects who have used tobacco products within 90 days of Period 1 dose administration.
• Subjects who report donating greater than 150 mL of blood within 14 days prior to dosing.
• Subjects who report receiving any investigational drug within 28 days prior to dosing.
• Subjects who report taking any systemic prescription medication in the 14 days prior to dosing.
• Subjects who report an intolerance of direct venipuncture.
• Subjects who report consuming an abnormal diet within the 28 days prior to dosing.

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
Experimental: Generic Test Product; Losartan potassium/Hydrochlorothiazide 100/25 mg Tablets	Drug: Losartan potassium/Hydrochlorothiazide; 100/25 mg Tablets
Active Comparator: Reference Listed Drug; Hyzaar® 100/25 mg Tablets	Drug: Hyzaar®; 100/25 mg Tablets; Other Names: Losartan potassium/Hydrochlorothiazide (generic name)

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 48 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 48 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 48 hour period.
AUC0-t of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)	Bioequivalence based on Hydrochlorothiazide AUC0-t.	Blood samples collected over a 48 hour period.
AUC0-inf of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Infinity)	Bioequivalence based on Hydrochlorothiazide AUC0-inf.	Blood samples collected over a 48 hour period.
Cmax of Hydroclorothiazide(Maximum Observed Concentration of Drug Substance in Plasma)	Bioequivalence based on Hydrochlorothiazide Cmax.	Blood samples collected over a 48 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 48 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 48 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 Losartan Carboxy Acid.	Blood samples collected over a 48 hour period.

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): February 1, 2004
• Study Completion (Actual): February 1, 2004

Study Registration Dates

• First Submitted: June 21, 2010
• First Submitted That Met QC Criteria: June 22, 2010
• First Posted (Estimate): June 23, 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: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Losartan; Hydrochlorothiazide
• Other Study ID Numbers: R04-080