Clinical trial NCT01124162: Losartan 100 mg Tablets in Healthy Subjects Under Fasting Conditions
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Bioequivalence
Healthy Subjects
Lead sponsor: Teva Pharmaceuticals USA
Sponsor class: INDUSTRY
First posted: 2010-05-14
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.

Detailed description: Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA Bioequivalence Statistical Methods

Eligibility criteria: 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).

Primary outcomes:
measure: Cmax of Losartan (Maximum Observed Concentration of Drug Substance in Plasma)
timeFrame: Blood samples collected over a 24 hour period.
measure: AUC0-t of Losartan (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
timeFrame: Blood samples collected over a 24 hour period.
measure: AUC0-inf of Losartan (Area Under the Concentration-time Curve From Time Zero to Infinity)
timeFrame: Blood samples collected over a 24 hour period.
Secondary outcomes:
measure: Cmax of Losartan Carboxy Acid (Maximum Observed Concentration of Drug Substance in Plasma)
timeFrame: Blood samples collected over a 24 hour period.
measure: AUC0-t of Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
timeFrame: Blood samples collected over a 24 hour period.
measure: AUC0-inf of Losartan Carboxy Acid(Area Under the Concentration-time Curve From Time Zero to Infinity)
timeFrame: Blood samples collected over a 24 hour period.
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Anapharm Inc.
state: Quebec
Study officials:
affiliation: Anapharm
name: Richard Larouche, MD
role: PRINCIPAL_INVESTIGATOR
References: