Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the relative bioavailability of Losartan potassium/Hydrochlorothiazide 100/25 mg tablets (manufactured by Teva Pharmaceutical Industries, Ltd. and distributed by Teva Pharmaceuticals USA) with that of Hyzaar® 100/25 mg tablets (Merck) in healthy, adult, non-smoking subjects under non-fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods
Interventions
100/25 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
* Healthy, non-smoking, male and female subjects at least 18 years of age. * BMI (body mass index) of 30 or less. * Females in this study must be physically unable to become pregnant (postmenopausal for at least 6 months or surgically sterile). * Successful completion of a physical examination within 28 days of initiation of the study. * Negative serum pregnancy test (females).
Exclusion criteria
* Subjects with a significant recent history of chronic alcohol consumption (past 2 years), drug addiction, or serious gastrointestinal, renal, hepatic, or cardiovascular disease, tuberculosis, epilepsy, asthma (past 5 years), diabetes, psychosis, or glaucoma will not be eligible for this study. * Subjects whose clinical laboratory test values are outside the reference range and are deemed clinically significant by the Principle Investigator. * Subjects who have a history of allergic responses to the classes of drugs being tested will be excluded from the study. * Subjects who use tobacco in any form will not be eligible to participate in the study. 3 months abstinence is required. * Subjects found to have urine concentrations of any of the tested drugs of abuse will not be allowed to participate. * Subjects should not have donated blood and/or plasma for at least 30 days prior to the first dosing of the study. * Subjects who have taken any investigational drug within 30 days prior to the first dosing of the study will not be allowed to participate. * Female subjects who are pregnant or who are able (women with child bearing potential) to become pregnant during the study will not be allowed to participate. * All female subjects will be screened for pregnancy at check-in each study period. Subjects with positive or inconclusive results will be withdrawn from the study. * Subjects who do not tolerate venipuncture will not be allowed to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Losartan(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 48 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 48 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 48 hour period. | Bioequivalence based on Losartan AUC0-inf. |
| Cmax of Hydrochlorothiazide(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 48 hour period. | Bioequivalence based on Hydrochlorothiazide Cmax. |
| AUC0-t of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 48 hour period. | Bioequivalence based on Hydrochlorothiazide AUC0-t. |
| AUC0-inf of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 48 hour period. | Bioequivalence based on Hydrochlorothiazide AUC0-inf. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan/HCTZ (Test) First 100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in first period followed by 100/25 mg Hyzaar® Tablets reference product dosed in the second period. | 40 |
| Hyzaar® (Reference) First 100/25 mg Hyzaar® Tablets reference product dosed in first period followed by 100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in the second period. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 1 |
| Washout of 7 Days | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Losartan/HCTZ (Test) First | Hyzaar® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 39 Participants | 79 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Black | 3 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized Caucasian | 35 participants | 36 participants | 71 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 33 Participants | 33 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 80 | 0 / 80 |
| serious Total, serious adverse events | 0 / 80 | 0 / 80 |
Outcome results
Primary
AUC0-inf of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on Hydrochlorothiazide AUC0-inf.
Time frame: Blood samples collected over a 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/HCTZ (Test) | AUC0-inf of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Infinity) | 943.22 ng*h/mL | Standard Deviation 217.842 |
| Hyzaar® (Reference) | AUC0-inf of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Infinity) | 945.592 ng*h/mL | Standard Deviation 217.269 |
90% CI: [98.7, 101]
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 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/HCTZ (Test) | AUC0-inf of Losartan(Area Under the Concentration-time Curve From Time Zero to Infinity) | 957.445 ng*h/mL | Standard Deviation 465.781 |
| Hyzaar® (Reference) | AUC0-inf of Losartan(Area Under the Concentration-time Curve From Time Zero to Infinity) | 956.046 ng*h/mL | Standard Deviation 467.567 |
90% CI: [98.6, 104]
Primary
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.
Time frame: Blood samples collected over a 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/HCTZ (Test) | AUC0-t of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 917.034 ng*h/mL | Standard Deviation 212.109 |
| Hyzaar® (Reference) | AUC0-t of Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 919.631 ng*h/mL | Standard Deviation 210.684 |
95% CI: [98.6, 101]
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 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/HCTZ (Test) | AUC0-t of Losartan(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 959.41 ng*h/mL | Standard Deviation 480.988 |
| Hyzaar® (Reference) | AUC0-t of Losartan(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 939.492 ng*h/mL | Standard Deviation 465.001 |
90% CI: [98.8, 106]
Primary
Cmax of Hydrochlorothiazide(Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Hydrochlorothiazide Cmax.
Time frame: Blood samples collected over a 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/HCTZ (Test) | Cmax of Hydrochlorothiazide(Maximum Observed Concentration of Drug Substance in Plasma) | 136.361 ng/mL | Standard Deviation 33.311 |
| Hyzaar® (Reference) | Cmax of Hydrochlorothiazide(Maximum Observed Concentration of Drug Substance in Plasma) | 132.717 ng/mL | Standard Deviation 35.468 |
90% CI: [98.8, 108]
Primary
Cmax of Losartan(Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Losartan Cmax.
Time frame: Blood samples collected over a 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan/HCTZ (Test) | Cmax of Losartan(Maximum Observed Concentration of Drug Substance in Plasma) | 458.29 ng/mL | Standard Deviation 323.345 |
| Hyzaar® (Reference) | Cmax of Losartan(Maximum Observed Concentration of Drug Substance in Plasma) | 409.324 ng/mL | Standard Deviation 251.876 |
90% CI: [98.1, 120]