Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the relative bioavailability of Moexipril HCl/hydrochlorothiazide 15/25 mg tablets (manufactured and distributed by TEVA Pharmaceuticals USA) with that of UNIRETIC® 15/25 mg tablets (Schwartz Pharma) in healthy, adult non-smoking subjects under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 15/25 mg
1 x 15/25 mg
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
* All subjects selected for this study will be non-smokers at least 18 years of age. * Subjects will have a BMI index (body mass index) of 30 or less.
Exclusion criteria
* Subjects with a history of chronic alcohol consumption (during past 2 years), drug addiction, or serious gastrointestinal, renal, hepatic, tuberculosis, epilepsy, asthma (during past 5 years), diabetes, psychosis or glaucoma will not be eligible for this study. * Subjects whose clinical laboratory test values are greater than 20% outside the normal range may be retested. If the clinical values are outside the range on retesting, the subject will not be eligible to participate in the study unless the clinical investigator deems the result not to be significant. * Subjects who have a history of allergic responses to the class of drug being tested should be excluded from the study. * All subjects will have urine samples assayed for the presence of abuse as part of the clinical laboratory screening procedures and ath check-in each study period. Subjects found to have urine concentrations of any of the tested drug will not be allowed to participate. * Subjects should not have donated blood and/or plasma for at least thirty (30) days prior to the first dosing of the study. * Subjects who have taken an investigational drug within thirty (30) days prior to the first dosing of the study will not be allowed to participate. * Female subjects who are pregnant, breast-feeding, or who are likely to become pregnant during the study will not be allowed to participate. Female subjects of child bearing potential must either abstain from sexual intercourse or use a reliable barrier method (e.g. condom, IUD) of contraception during the course of the study (first dosing until last blood collection) or they will not be allowed to participate. Subjects who have used implanted or injected hormonal contraceptives anytime during the 180 days prior to study dosing or oral hormonal contraceptives with in 14 days of dosing 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 use tobacco in any form will not be eligible to participate in the study. Three months abstinence is required. * Subjects who do not tolerate venipuncture will not be allowed to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Hydrochlorothiazide. | Blood samples collected over a 192 hour period. | Bioequivalence based on AUC0-inf. |
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexipril. | Blood samples collected over a 192 hour period. | Bioequivalence based on AUC0-inf. |
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Hydrochlorothiazide. | Blood samples collected over a 192 hour period. | Bioequivalence based on Cmax. |
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Hydrochlorothiazide. | Blood samples collected over a 192 hour period. | Bioequivalence based on AUC0-t. |
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexipril. | Blood samples collected over a 192 hour period. | Bioequivalence based on Cmax. |
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexipril. | Blood samples collected over a 192 hour period. | Bioequivalence based on AUC0-t. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexiprilat. | Blood samples collected over a 192 hour period. | Informational comparison of AUC0-t values for the metabolite Moexiprilat. |
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexiprilat. | Blood samples collected over a 192 hour period. | Informational comparison of AUC0-inf values for the metabolite Moexiprilat. |
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexiprilat. | Blood samples collected over a 192 hour period. | Informational comparison of Cmax values for the metabolite Moexiprilat. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test (Moexipril HCl/HCTZ) First 15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in first period followed by 15/25 mg Uniretic® Tablets reference product dosed in the second period. | 30 |
| Reference (Uniretic®) First 15/25 mg Uniretic® Tablets reference product dosed in first period followed by 15/25 mg Moexipril HCl/Hydrochlorothiazide test product dosed in the second period. | 28 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 2 |
| First Intervention | Withdrawal by Subject | 3 | 0 |
| Washout of 21 Days | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Test (Moexipril HCl/HCTZ) First | Reference (Uniretic®) 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 | 30 Participants | 28 Participants | 58 Participants |
| Race/Ethnicity, Customized Black | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 28 participants | 25 participants | 53 participants |
| Region of Enrollment United States | 30 participants | 28 participants | 58 participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Outcome results
Primary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Hydrochlorothiazide.
Bioequivalence based on AUC0-inf.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Hydrochlorothiazide. | 1001.133 ng*h/mL | Standard Deviation 308.857 |
| Reference (Uniretic®) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Hydrochlorothiazide. | 1001.548 ng*h/mL | Standard Deviation 282.322 |
90% CI: [96.7, 102]
Primary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexipril.
Bioequivalence based on AUC0-inf.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexipril. | 55.837 ng*h/mL | Standard Deviation 31.874 |
| Reference (Uniretic®) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexipril. | 54.593 ng*h/mL | Standard Deviation 28.107 |
90% CI: [92.3, 106]
Primary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Hydrochlorothiazide.
Bioequivalence based on AUC0-t.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Hydrochlorothiazide. | 992.17 ng*h/mL | Standard Deviation 309.57 |
| Reference (Uniretic®) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Hydrochlorothiazide. | 994.093 ng*h/mL | Standard Deviation 282.294 |
90% CI: [96.4, 102]
Primary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexipril.
Bioequivalence based on AUC0-t.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexipril. | 54.517 ng*h/mL | Standard Deviation 31.582 |
| Reference (Uniretic®) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexipril. | 53.598 ng*h/mL | Standard Deviation 28.028 |
90% CI: [92.2, 106]
Primary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Hydrochlorothiazide.
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Hydrochlorothiazide. | 153.602 ng/mL | Standard Deviation 54.048 |
| Reference (Uniretic®) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Hydrochlorothiazide. | 145.088 ng/mL | Standard Deviation 43.864 |
90% CI: [99.3, 111]
Primary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexipril.
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexipril. | 31.913 ng/mL | Standard Deviation 15.761 |
| Reference (Uniretic®) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexipril. | 34.4 ng/mL | Standard Deviation 17.4 |
90% CI: [85.8, 99.8]
Secondary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexiprilat.
Informational comparison of AUC0-inf values for the metabolite Moexiprilat.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexiprilat. | 443.448 ng*h/mL | Standard Deviation 121.714 |
| Reference (Uniretic®) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexiprilat. | 427.212 ng*h/mL | Standard Deviation 136.2 |
90% CI: [97.6, 108]
Secondary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexiprilat.
Informational comparison of AUC0-t values for the metabolite Moexiprilat.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexiprilat. | 262.231 ng*h/mL | Standard Deviation 73.413 |
| Reference (Uniretic®) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexiprilat. | 264.991 ng*h/mL | Standard Deviation 75.409 |
90% CI: [94.6, 103]
Secondary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexiprilat.
Informational comparison of Cmax values for the metabolite Moexiprilat.
Time frame: Blood samples collected over a 192 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Moexipril HCl/HCTZ) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexiprilat. | 20.049 ng/mL | Standard Deviation 10.751 |
| Reference (Uniretic®) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexiprilat. | 21.882 ng/mL | Standard Deviation 14.497 |
90% CI: [81.8, 101]