Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
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 fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods
Interventions
DRUGLosartan
100 mg Tablets
DRUGCozaar®
100 mg Tablets
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Non-child-bearing potential female or male. * Non-smoker * 18 years or 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. * ECG abnormalities (clinically significant) or vital sign abnormalities at screening. * Subjects with BMI greater than or equal to 30.0. * History of significant alcohol abuse within 6 months prior to the screening visit or any indication of the regular use of more than 14 units of alcohol per week (1 unit equals 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol). * History of drug abuse of use of illegal drugs: use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine \[PCP\], or 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 of 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, unresolved gastrointestinal symptoms, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug. * Any clinically significant history or presence of 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 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 the 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 subject's participation in this study. * A depot 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 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 within 7 days prior to administration of the study medication. * Clinically significant history or known hypotension or volume depletion. * Intolerance to venipuncture. * Clinically significant history or renal, hepatic, or cardiovascular disease, tuberculosis, epilepsy, asthma, diabetes, psychosis, or glaucoma will not be eligible for this study. * Subjects who are unable to understand or unwilling to sign the Informed Consent Form. * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Losartan (Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 24 hour period. | Bioequivalence based on Losartan Cmax. |
| AUC0-t of Losartan (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 24 hour period. | Bioequivalence based on Losartan AUC0-t. |
| AUC0-inf of Losartan (Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 24 hour period. | Bioequivalence based on Losartan AUC0-inf. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Losartan Carboxy Acid (Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 24 hour period. | Informational comparison of Cmax values for the metabolite Losartan Carboxy Acid. |
| AUC0-t of Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 24 hour period. | Informational comparison of AUC0-t values for the metabolite Losartan Carboxy Acid. |
| AUC0-inf or Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 24 hour period. | Informational comparison of AUC0-inf values for the metabolite Losartan Carboxy Acid. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan (Test) First 100 mg Losartan tablets test product dosed in first period followed by 100 mg Cozaar® Tablets reference product dosed in the second period. | 40 |
| Cozaar® (Reference) First 100 mg Cozaar® Tablets reference product dosed in first period followed by 100 mg Losartan Tablets test product dosed in the second period. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout of 7 Days | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Losartan (Test) First | Cozaar® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 38 Participants | 75 Participants |
| Race/Ethnicity, Customized Black | 3 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized Caucasian | 36 participants | 35 participants | 71 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 3 participants | 4 participants |
| Region of Enrollment Canada | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 13 Participants | 23 Participants | 36 Participants |
| Sex: Female, Male Male | 27 Participants | 17 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 80 | 3 / 80 |
| serious Total, serious adverse events | 0 / 80 | 0 / 80 |
Outcome results
Primary
AUC0-inf of Losartan (Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on Losartan AUC0-inf.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed. However, one subject had a baseline concentration greater than 5% of Cmax and therefore was not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan (Test) | AUC0-inf of Losartan (Area Under the Concentration-time Curve From Time Zero to Infinity) | 926.82 ng*h/mL | Standard Deviation 274.16 |
| Cozaar® (Reference) | AUC0-inf of Losartan (Area Under the Concentration-time Curve From Time Zero to Infinity) | 877.73 ng*h/mL | Standard Deviation 264.17 |
90% CI: [103.32, 108.07]
Primary
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.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed. However, one subject had a baseline concentration greater than 5% of Cmax and therefore was not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan (Test) | AUC0-t of Losartan (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 915.12 ng*h/mL | Standard Deviation 271.7 |
| Cozaar® (Reference) | AUC0-t of Losartan (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 864.29 ng*h/mL | Standard Deviation 260.73 |
90% CI: [103.61, 108.39]
Primary
Cmax of Losartan (Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Losartan Cmax.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed. However, one subject had a baseline concentration greater than 5% of Cmax and therefore was not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan (Test) | Cmax of Losartan (Maximum Observed Concentration of Drug Substance in Plasma) | 407.66 ng/mL | Standard Deviation 209.45 |
| Cozaar® (Reference) | Cmax of Losartan (Maximum Observed Concentration of Drug Substance in Plasma) | 360.82 ng/mL | Standard Deviation 183.42 |
90% CI: [101.84, 123.06]
Secondary
AUC0-inf or 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.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan (Test) | AUC0-inf or Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Infinity) | 3679.30 ng*h/mL | Standard Deviation 1065.16 |
| Cozaar® (Reference) | AUC0-inf or Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Infinity) | 3607.01 ng*h/mL | Standard Deviation 1119.74 |
90% CI: [100.41, 104.34]
Secondary
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.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan (Test) | AUC0-t of Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 3556.41 ng*h/mL | Standard Deviation 1032.48 |
| Cozaar® (Reference) | AUC0-t of Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 3453.09 ng*h/mL | Standard Deviation 1041.97 |
90% CI: [100.9, 105.28]
Secondary
Cmax of Losartan Carboxy Acid (Maximum Observed Concentration of Drug Substance in Plasma)
Informational comparison of Cmax values for the metabolite Losartan Carboxy Acid.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan (Test) | Cmax of Losartan Carboxy Acid (Maximum Observed Concentration of Drug Substance in Plasma) | 587.80 ng/mL | Standard Deviation 196.59 |
| Cozaar® (Reference) | Cmax of Losartan Carboxy Acid (Maximum Observed Concentration of Drug Substance in Plasma) | 560.83 ng/mL | Standard Deviation 210.92 |
90% CI: [101.22, 110.93]