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| Name | Class |
|---|---|
| ClinPharmInvest, LLC | OTHER |
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This is an open-labeled (laboratory blinded), randomized, two period, single-center, crossover, comparative study, where each participant will be randomly assigned to the reference (Zestril®, 20 mg) or the test (Lisinopril, 20 mg) formulation in each period of study (sequences Test-Reference (TR) or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence TR | Other | 19 subjects assigned to the sequence TR will receive a single 20 mg dose of the test product Lisinopril (1 x 20 mg tablet), marked as T in the sequence, in Period 1 and a single 20 mg dose of the reference product Zestril® (1 x 20 mg tablet), marked as R in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken. |
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| Sequence RT | Other | 19 subjects assigned to the sequence RT will receive a single 20 mg dose of the reference product Zestril® (1 x 20 mg tablet), marked as R in the sequence, in Period 1 and a single 20 mg dose of the test product Lisinopril (1 x 20 mg tablet), marked as T in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lisinopril tablet 20 mg | Drug | Lisinopril is manufactured by Pharmtechnology LLC, Belarus. Each tablet contains 20 mg of lisinopril. |
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| Measure | Description | Time Frame |
|---|---|---|
| Cmax of lisinopril in plasma after administration of the test and the reference products. | Maximum observed concentration in plasma. | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
| AUC0-t of lisinopril in plasma after administration of the test and the reference. | Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method. | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Tmax of lisinopril in plasma after administration of the test and the reference products. | Tmax of lisinopril in plasma after administration of the test and the reference products. | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
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Inclusion Criteria:
Healthy caucasian men and women aged between 18 to 45 years
Verified diagnosis "healthy" according to the anamnesis data and the results of standard clinical, laboratory and instrumental examination methods, physical examination and anamnestic examination
The results of an X-ray or fluorographic examination of the chest organs within the normal range (the results of an examination carried out within 12 months before the start of the study may be provided)
Satisfactory tolerance of the orthostatic test (the range of increase in heart rate when moving from a prone position to a standing position within 12 - 18 beats per minute)
Body mass index 18.5-30 kg/m² according to Quetelet's weight-height index
For female subject:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alexander Khokhlov | ClinPharmInvest, LLC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Private healthcare institution "Clinical Hospital "RZD-Medicine" of the city of Yaroslavl" | Yaroslavl | Yaroslavl Oblast | 150047 | Russia |
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| ID | Term |
|---|---|
| D017706 | Lisinopril |
| ID | Term |
|---|---|
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Zestril® tablet 20 mg | Drug | Zestril® is manufactured by Avara Reims Pharmaceutical Services, France. Each tablet contains 20 mg of lisinopril. |
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| TLQC of lisinopril in plasma after administration of the test and the reference products. | Time of last observed quantifiable concentration. | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
| AUC0-INF of lisinopril in plasma after administration of the test and the reference products. | Area under the concentration time curve extrapolated to infinity, calculated as AUC0-t + ĈLQC (the predicted concentration at time TLQC) / λZ (apparent elimination rate constant). | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
| Residual area of lisinopril in plasma after administration of the test and the reference products. | Extrapolated area (i.e. percentage of AUC0-INF due to extrapolation from TLQC to infinity). | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
| Time point where the log-linear elimination phase begins (TLIN) of lisinopril in plasma after administration of the test and the reference products. | Time point where the log-linear elimination phase begins. | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
| λZ of lisinopril in plasma after administration of the test and the reference products. | Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus time curve. | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
| Terminal elimination half-life (Thalf) of lisinopril in plasma after administration of the test and the reference products. | Terminal elimination half-life, calculated as ln(2)/λZ. | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |
| Number of treatment-emergent adverse events for the test and the reference products. | The safety population will include all subjects who received at least one dose of the test or the reference product. Any significant changes will be recorded as treatment-emergent adverse events only if they are judged clinically significant by the qualified investigator or delegate. | Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration. |