Bioequivalence Study For 5 Mg Amlodipine Orally-Disintegrating Tablet

Study Overview
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Brief Summary
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This study is being conducted to determine if 5 mg amlodipine 3rd Orally-Disintegrating (OD) tablet (new formulation) and 5 mg amlodipine 2nd OD tablet (commercial formulation) are bioequivalent.

Official Title
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An Open, Randomized, Parallel-Cohort, 2-Periods, Crossover, Single Dose Bioequivalence Study For 5 Mg Amlodipine Orally-Disintegrating Tablet In Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Amlodipine
* Drug: Amlodipine
* Drug: Amlodipine
* Drug: Amlodipine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy; Body Mass Index (BMI) of 18 to 28 kg/m2; total body weight within the range of 50 to 100 kg Exclusion Criteria: History of regular alcohol consumption exceeding 14 drinks/week Use of tobacco- or nicotine-containing products in excess of the equivalent of 10 cigarettes per day

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>24 subjects (12 subjects per sequence) will receive treatment A) one 5 mg amlodipine 3rd OD tablet (test) with water and treatment B) one 5 mg amlodipine 2nd OD tablet (reference) with water. | Drug: Amlodipine<br>* 3rd OD 5 mg tablet single oral dose administered with water<br>Drug: Amlodipine<br>* 2nd OD 5 mg tablet single oral dose administered with water<br>|
| Active Comparator: Cohort 2<br>24 subjects (12 subjects per sequence) will receive treatment C) one 5 mg amlodipine 3rd OD tablet (test) without water, and treatment D) one 5 mg amlodipine 2nd OD tablet (reference) without water | Drug: Amlodipine<br>* 3rd OD 5 mg tablet single oral dose administered without water<br>Drug: Amlodipine<br>* 2nd OD 5 mg tablet single oral dose administered without water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve From Zero Time Until the Last Sampling Time (AUCt) | Area under the concentration-time curve from zero time until the last sampling time | prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) |  | prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast), Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf) | AUC last = Area under the concentration versus time curve from zero time until the last measurable concentration is calculated using the trapezoidal rule. AUCinf = AUClast + (Ct / kel), where Ct is the estimated concentration at the last measurable concentration. | prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose | 
| Apparent Terminal Elimination Phase Rate Constant (Kel) | Estimated as the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm (ln) transformed concentration-time profile. | prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose | 
| Apparent Terminal Elimination Half-Life (T-half) | Terminal phase half-life calculated as ln(2) / kel | prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose | 
| Mean Residence Time (MRT) | MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method. | prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose |