Comparison of Bioavailability of Dexketoprofen-Vit B vs Dexketoprofen, in Healthy Subjects, Under Fasting Conditions

Study Overview
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Brief Summary
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Bioavailability comparison study with a cross-over desing, 2x2, open, prospective and longitudinal, at a single dose with two treatments, two periods, two sequences with an elimination (washout) period of 7 days and a number of 36 healthy subjects, of both genders, under fasting conditions, of reference tablets of Dexketoprofen 25 mg (Stadium®), elaborated by Grimann, S.A. de C.V., and capsule test drug with Dexketoprofen 25 mg- Vitamin B complex elaborated by Laboratorios Silanes S.A. de C.V.

Detailed Description
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The study was designed to recruit 36 healthy subjects considering a 2x2 design, where each subject received both treatments and was its own control. The time was adjusted considering the half-life of the drugs to be evaluated. Healthy subjects of both genders were selected since no relevant pharmacokinetic differences related to gender had been reported for the study drug. The aim of the study was to comparatively evaluate, in the same individuals the plasma concentrations of Dexketoprofen 25 mg from two pharmaceutical formulations; reference tablets of Dexketoprofen 25 mg ( Stadium®), elaborated by Grimann, S.A. de C.V., and capsule test drug with Dexketoprofen 25 mg- Vitamin B complex elaborated by Laboratorios Silanes S.A. de C.V.

Official Title
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Comparison of Bioavailability of Dexketoprofen-Vit B vs Dexketoprofen (Stadium®), Dose 25 mg in Healthy Subjects, of Both Genders, Under Fasting Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dexketoprofen 25 MG
* Drug: Fixed dose Dexketoprofen-Vitamin B Complex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: That the patient gives informed consent in writing. Be accepted by the COFEPRIS research subjects registry base. Subjects without subordination relationship with the researchers or sponsor. - Subjects of both genders, aged between 18 and 55, Mexican. No history of hypersensitivity or related drug allergies. Body mass index between 18 and 27 kg / m2 Healthy subjects, according to the results of the complete clinical history, electrocardiogram and the integration of the results of the clinical analyzes, carried out in certified clinical laboratories, without alterations that, at the discretion of the Principal Investigator, require medical intervention as a consequence. Subjects with negative results for immunological tests (Anti-HIV (Human immunodeficiency virus), Anti-hepatitis B and C, VDRL (venereal disease reaction level)). Subjects with negative results in qualitative tests for the detection of drugs of abuse: tetrahydro-cannabinoids, cocaine and Research subject that presents alterations in the vital signs recorded during the selection.amphetamines. Negative (qualitative) pregnancy test in the case of women of childbearing age without bilateral tubal obstruction or hysterectomy. In the case of women of childbearing age, the subject must sign a letter of commitment not to pregnancy and have a birth control method, including barrier methods, non-hormonal intrauterine device or bilateral tubal obstruction. Exclusion Criteria: Subjects with a recent history (3 months) or evidence on physical examination of gastrointestinal, renal, hepatic, endocrine, respiratory, cardiovascular, dermatological or hematological disease that could affect the pharmacokinetic study of the investigational product. Subjects who have been exposed to drugs known as liver enzyme inducers or inhibitors or who have taken potentially toxic drugs within 30 days prior to the start of the study. Subjects who have received any medication for 7 days prior to the start of the study. Subjects who have been hospitalized for any problem during the three months prior to the start of the study. Subjects who have been rejected for their registration in the COFEPRIS research subject registry database, for having participated in a clinical study within the three months prior to the start of the study. Subjects who have received investigational drugs within 60 days prior to the study. Subjects allergic to the drug under study or related drugs. Subjects who have ingested alcohol or beverages containing xanthines (coffee, tea, cocoa, chocolate, cola soft drinks) or who have ingested charcoal-grilled foods or grapefruit or cranberry juice, at least 10 hours before the start of the study or who have smoked tobacco within 24 hours prior to the start of the internment period. Subjects who have donated or lost 450 mL or more of blood within the 60 days prior to the start of the study. Subjects with a history of drug and / or alcohol abuse according to the DSM-IV-TR ( Diagnostic and Statistical Manual of Mental Disorders) Criteria.

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 |
| --- | --- |
| Active Comparator: Group A: Dexketoprofen (Stadium®)<br>Reference Drug Pharmaceutical Form: Tablets Dosage: 25 mg Administration way: oral | Drug: Dexketoprofen 25 MG<br>* Pharmaceutical Form: Tablets Dosage: 25 mg Adminstration way: Oral<br>* Other names: (Stadium®);|
| Experimental: Group B: Fixed dose Dexketoprofen-Vitamin B Complex<br>Fixed dose combination: Pharmaceutical Form: capsule Dosage: 25 mg of Dexketoprofen + Cyanocobalamin, Thiamine,and Pyridoxine. Administration way: oral | Drug: Fixed dose Dexketoprofen-Vitamin B Complex<br>* Pharmaceutical Form: capsule Dosage: 25 mg of Dexketoprofen + Cyanocobalamin 500 µg, Thiamine 100 mg, Pyridoxine 50 mg. Administration way: oral<br>* Other names: DEXK / VITB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration following the treatment (Cmax) | Evaluate the fixed dose pharmacokinetics profile of Dexketoprofen-Vitamin B, employing the maximum observed concentration following the treatment (Cmax). | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 14.00 and 24.00 hours | 
| The area under the curve from time zero to the last measurable concentration (AUC 0-t) | Evaluate the fixed dose pharmacokinetics profile of Dexketoprofen-Vitamin B, employing the area under the curve from time zero to the last measurable concentration (AUC 0-t)using the linear trapezoidal method. | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 14.00 and 24.00 hours | 
| The area under the curve from time zero to infinity calculated (AUC 0-inf) | Evaluate the fixed dose pharmacokinetics profile of Dexketoprofen-Vitamin B, employing the area under the curve from time zero to infinity (AUC 0-inf), estimated by adding the quotient of the last concentration measured between ke. | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 14.00 and 24.00 hours | 
| Time of the maximum measured concentration (Tmax). | Evaluate the fixed dose pharmacokinetics profile of Dexketoprofen-Vitamin B, employing time of the maximum measured concentration (Tmax) | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 14.00 and 24.00 hours | 
| Elimination rate (Ke) | Evaluate the fixed dose pharmacokinetics profile of Dexketoprofen-Vitamin B, employing the elimination rate (Ke), calculated by log-linear regression of the final phase of elimination | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 14.00 and 24.00 hours | 
| Elimination half-life (t 1/2) | Evaluate the fixed dose pharmacokinetics profile of Dexketoprofen-Vitamin B, employing the elimination half-life (t 1/2) by dividing 0.693 / ke. | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 14.00 and 24.00 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency of adverse events | The percentage of frequency of appearance of each adverse event was evaluated. | 2 days | 
| Adverse events | Any adverse event were classified by severity, treatment and its relationship with the study drug was evaluated. | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexketoprofen, Trometamol, Cyanocobalamin, Thiamine, Pyridoxine, Pharmacokinetic, Bioavailability, Fixed-dose combination (FDC), Bioequivalence