A Bioequivalence Study of Montelukast From Asmakast 10mg Tabs (Sandoz, Egypt) & Singulair 10mg Tabs (Merck)

Study Overview
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Brief Summary
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Comparative randomized, single dose, two-way crossover open-label study to determine the bioequivalence of Montelukast fromAsmakast10 mg tablets (Man. by Minapharm Egypt for Novartis Pharma Egypt S.A.E (Sandoz), Egypt) and Singulair10 mg tablets (Produced by Global Napi Pharmaceuticals, Egypt under license from: Merck & Co. Inc., USA) after a single oral dose administration of each to healthy adults under fasting conditions.

Detailed Description
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19 blood samples will be drawn in each period. The total volume of blood will not exceed 200 ml throughout the whole study.0.00 (pre-dose), 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00,2.50, 3.00,3.50, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, and 24.00 hours post dose. Primary Pharmacokinetic Parameters: Cmax, AUC0→t and AUC0→∞ Secondary Pharmacokinetic Parameters: Ke, tmax and t1/2e. ANOVA using 5% significance level for transformed (with the 90% confidence intervals) and untransformed data of Cmax, AUC0→t and AUC0→∞ and for untransformed data of Ke, tmax and t1/2e. The confidence intervals of logarithmically transformed Test/Reference ratios for Cmax, AUC0→t and AUC0→∞ to be within 80.00-125.00%. A comprehensive final report will be issued upon the completion of the study.

Official Title
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Comparative Open-label,Randomized, Fasting, Single Dose, Two-way Crossover Bioequivalence Study of Montelukast From Asmakast 10mg Tabs (Sandoz, Egypt) & Singulair® 10mg Tabs (Merck & Co, Egypt) to Healthy Adult Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Asmakast
* Drug: Singulair


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female, age 18 to 55 years, inclusive. Body weight within 15% of normal range according to the accepted normal values for body mass index (BMI). Medical demographics without evidence of clinically significant deviation from normal medical condition. Results of clinical laboratory test are within the normal range or with a deviation that is not considered clinically significant by principal investigator. Subject does not have allergy to the drugs under investigation. Exclusion Criteria: Subjects with known allergy to the products tested. Subjects whose values of BMI were outside the accepted normal ranges. Female subjects who are pregnant, nursing or taking birth control pills. Medical demographics with evidence of clinically significant deviation from normal medical condition. Results of laboratory tests which are clinically significant. Acute infection within one week preceding first study drug administration. History of drug or alcohol abuse. Subject does not agree not to take any prescription or non-prescription drugs within two weeks before first study drug administration and until the end of the study. Subject is on a special diet (for example subject is vegetarian). Subject does not agree not to consume any beverages or foods containing methyl-xanthenes e.g. caffeine (coffee, tea, cola, chocolate etc.) 48 hours prior to the study administration of either study period until donating the last sample in each respective period. Subject does not agree not to consume any beverages or foods containing grapefruit 7 days prior to first study drug administration until the end of the study. Subject has a history of severe diseases which have direct impact on the study. Participation in a bioequivalence study or in a clinical study within the last 6 weeks before first study drug administration. Subject intends to be hospitalized within 6 weeks after first study drug administration. Subjects who, through completion of this study, would have donated more than 500 ml of blood in 7 days, or 750 ml of blood in 30 days, 1000 ml in 90 days, 1250 ml in 120 days, 1500 ml in 180 days, 2000 ml in 270 days, 2500 ml of blood in 1 year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A Test<br>test drug (Asmakast)1 tablet contains 10 mg Montelukast | Drug: Asmakast<br>* 1 tablet contains 10 mg of montelukast<br>* Other names: Singulair;|
| Active Comparator: B Reference<br>reference drug (Singulair) 1 tablet contains 10 mg Montelukast | Drug: Singulair<br>* 1 tablet contains 10 mg of montelukast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal measured plasma concentration (Cmax) | Serial blood samples for determination of study drug will be collected pre-dose and at 0.00 (pre-dose), 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00,2.50, 3.00,3.50, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, and 24.00 hours postdose | 24 hours | 
| measurable concentration (t) (AUC [0 to t]) | (AUC [0 to t]) will be calculated by the linear trapezoidal method. | 24 hours | 
| Area Under the plasma concentration-time curve from time zero to infinity (AUC [0 to infinity]) | AUC (0 to infinity) will be calculated as the sum of the AUC (0 to t) plus the ratio of the last measurable plasma concentration to the elimination rate constant | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of the maximum plasma concentration (tmax)measurable concentration (t) (AUC [0 to t]) | If the Tmax occurs at more than time point, then tmax will be considered for the first occurrence.. | 24 hours | 
| Apparent first-order elimination or terminal rate constant (K¬e) | K¬e will be calculated from a semi-log plot of the plasma concentration versus time curve. The parameter will be calculated by linear least-squares regression analysis using the last three (or more) non-zero plasma concentrations | 24 hours | 
| Terminal half life (t1/2e) | The elimination or terminal half-life will be calculated as 0.693/ Ke | 24 hours |