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 fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods
Interventions
DRUGLosartan
100 mg Tablet
DRUGCozaar®
100 mg Tablet
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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 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
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 of 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 Losaran 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 |
|---|---|---|---|
| First Intervention | Adverse Event | 2 | 0 |
| Washout of 7 Days | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Losartan (Test) First | Cozaar® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 40 Participants | 80 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Caucasian | 32 participants | 36 participants | 68 participants |
| Race/Ethnicity, Customized Hispanic | 6 participants | 3 participants | 9 participants |
| Region of Enrollment Canada | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Male | 31 Participants | 31 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 80 | 9 / 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | AUC0-inf of Losartan (Area Under the Concentration-time Curve From Time Zero to Infinity) | 962.67 ng*h/mL | Standard Deviation 423.97 |
| Cozaar® | AUC0-inf of Losartan (Area Under the Concentration-time Curve From Time Zero to Infinity) | 947.18 ng*h/mL | Standard Deviation 419.38 |
90% CI: [98.41, 104.68]
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | AUC0-t of Losartan (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 950.90 ng*h/mL | Standard Deviation 422.61 |
| Cozaar® | AUC0-t of Losartan (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 934.24 ng*h/mL | Standard Deviation 418.99 |
90% CI: [98.57, 104.93]
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Cmax of Losartan (Maximum Observed Concentration of Drug Substance in Plasma) | 637.01 ng/mL | Standard Deviation 340.35 |
| Cozaar® | Cmax of Losartan (Maximum Observed Concentration of Drug Substance in Plasma) | 582.39 ng/mL | Standard Deviation 327.2 |
90% CI: [97.43, 120.03]
Secondary
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.
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 | AUC0-inf of Losartan Carboxy Acid(Area Under the Concentration-time Curve From Time Zero to Infinity) | 3855.02 ng*h/mL | Standard Deviation 1345.5 |
| Cozaar® | AUC0-inf of Losartan Carboxy Acid(Area Under the Concentration-time Curve From Time Zero to Infinity) | 3858.92 ng*h/mL | Standard Deviation 1352.83 |
90% CI: [97.87, 102.69]
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 | AUC0-t of Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 3748.87 ng*h/mL | Standard Deviation 1314.68 |
| Cozaar® | AUC0-t of Losartan Carboxy Acid (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 3750.39 ng*h/mL | Standard Deviation 1312.04 |
90% CI: [97.84, 102.84]
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 | Cmax of Losartan Carboxy Acid (Maximum Observed Concentration of Drug Substance in Plasma) | 658.17 ng/mL | Standard Deviation 272.35 |
| Cozaar® | Cmax of Losartan Carboxy Acid (Maximum Observed Concentration of Drug Substance in Plasma) | 647.22 ng/mL | Standard Deviation 259.27 |
90% CI: [98.24, 106.06]