Bioequivalence Study of 8 mg Perindopril Tert-Butylamine / 2.5 mg Indapamide / 10 mg Amlodipine Tablets Versus 10 mg Perindopril Arginine / 2.5 mg Indapamide / 10 mg Amlodipine Film-Coated Tablets in Healthy Volunteers

Study Overview
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Brief Summary
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The present study is a comparative bioavailability study performed to assess bioequivalence between a Test medication (PERINDOPRES® TRIO, 8 mg perindopril tert-butylamine / 2.5 mg indapamide / 10 mg amlodipine tablets manufactured by PrJSC Pharmaceutical firm Darnitsa [Ukraine]) and a Reference medication (marketed medicinal product TRIPLIXAM® 10 mg /2.5 mg/10 mg, 10 mg perindopril arginine / 2.5 mg indapamide / 10 mg amlodipine film-coated tablets [manufactured by Servier (Ireland) Industries Ltd]) in healthy adult volunteers under fasting conditions.

Official Title
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Randomized, Open-label, Single-dose, Two-sequence, Two-period, Crossover, Comparative, Oral Bioequivalence Study of Test Product PERINDOPRES® TRIO, 8 mg Perindopril Tert-Butylamine / 2.5 mg Indapamide/ 10 mg Amlodipine Tablets (PrJSC Pharmaceutical Firm Darnitsa) And Reference Product TRIPLIXAM® 10 mg /2.5 mg/10 mg, 10 mg Perindopril Arginine / 2.5 mg Indapamide / 10 mg Amlodipine Film-Coated Tablets (Manufactured By Servier (Ireland) Industries Ltd) In Healthy, Adult Subjects Under Fasting Conditions

Conditions
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Bioequivalence, Healthy Subjects

Intervention / Treatment
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* Drug: PERINDOPRES® TRIO, 8 mg perindopril tert-butylamine / 2.5 mg indapamide / 10 mg amlodipine tablets
* Drug: TRIPLIXAM® 10 mg /2.5 mg/10 mg, 10 mg perindopril arginine / 2.5 mg indapamide / 10 mg amlodipine film-coated tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects, age 18 to 50 years, inclusive, body mass index (BMI) range is within 18.5 - 30.0 kg/m2, subject does not have a known allergy to the drug under investigation or any of its ingredients or any other related drugs, standard ECG assessment is normal (no QTc prolongation), medical history and physical examination within medically acceptable criteria, laboratory investigations tests within laboratory reference ranges (ALP and creatinine are accepted if below the reference range after being evaluated by the physician as clinically not significant). Haematology tests within 5% of reference limits.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Two-period, two-sequence, cross-over single dose study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PERINDOPRES® TRIO (Test)<br>A single oral dose of the test product PERINDOPRES® TRIO 8 mg perindopril tert-butylamine / 2.5 mg indapamide / 10 mg amlodipine tablets. | Drug: PERINDOPRES® TRIO, 8 mg perindopril tert-butylamine / 2.5 mg indapamide / 10 mg amlodipine tablets<br>* Oral, generic fixed-dose combination of perindopril tert-butylamine (angiotensin-converting-enzyme inhibitor for the treatment of high blood pressure and heart failure), indapamide (thiazide-like diuretic used in the treatment of hypertension and decompensated heart failure) and amlodipine (calcium channel blocker used to treat high blood pressure and coronary artery disease).<br>|
| Active Comparator: TRIPLIXAM® 10 mg /2.5 mg/10 mg<br>A single oral dose of the reference product TRIPLIXAM® 10 mg /2.5 mg/10 mg, 10 mg perindopril arginine / 2.5 mg indapamide / 10 mg amlodipine film-coated tablets. | Drug: TRIPLIXAM® 10 mg /2.5 mg/10 mg, 10 mg perindopril arginine / 2.5 mg indapamide / 10 mg amlodipine film-coated tablets<br>* Oral, innovative fixed-dose combination of perindopril arginine (angiotensin-converting-enzyme inhibitor for the treatment of high blood pressure and heart failure), indapamide (thiazide-like diuretic used in the treatment of hypertension and decompensated heart failure) and amlodipine (calcium channel blocker used to treat high blood pressure and coronary artery disease).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of perindopril | The Cmax value is based on perindopril plasma concentration. | Blood sampling for pharmacokinetic analysis covered up to 36 hours post-dose | 
| Area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) of perindopril | The AUC0-t is the area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (t) and is based on perindopril plasma concentration. | Blood sampling for pharmacokinetic analysis covered up to 36 hours post-dose | 
| Cmax of indapamide | The Cmax value is based on indapamide plasma concentration. | Blood sampling for pharmacokinetic analysis covered up to 72 hours post-dose | 
| AUC0-t of indapamide | The AUC0-t is the area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (t) and is based on indapamide plasma concentration. | Blood sampling for pharmacokinetic analysis covered up to 72 hours post-dose | 
| Cmax of amlodipine | The Cmax value is based on amlodipine plasma concentration. | Blood sampling for pharmacokinetic analysis covered up to 72 hours post-dose | 
| Area under the concentration-time curve from time zero to 72 hours (AUC0-72) of amlodipine | The AUC0-72 is the area under the plasma concentration versus time curve from time zero (predose) to 72 hours and is based on amlodipine plasma concentration. | Blood sampling for pharmacokinetic analysis covered up to 72 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioequivalence, perindopril, indapamide, amlodipine, healthy subjects, pharmacokinetics