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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dexketoprofen 25 MG; Drug: Fixed dose Dexketoprofen-Vitamin B Complex

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Mexico City
    • Ciudad de Mexico, Mexico City, Mexico, 11000
      • Laboratorio Silanes, S.A. de C.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A: Dexketoprofen (Stadium®); Reference Drug Pharmaceutical Form: Tablets Dosage: 25 mg Administration way: oral	Drug: Dexketoprofen 25 MG; Pharmaceutical Form: Tablets Dosage: 25 mg Adminstration way: Oral; Other Names: (Stadium®)
Experimental: Group B: Fixed dose Dexketoprofen-Vitamin B Complex; 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; Pharmaceutical Form: capsule Dosage: 25 mg of Dexketoprofen + Cyanocobalamin 500 µg, Thiamine 100 mg, Pyridoxine 50 mg. Administration way: oral; Other Names: DEXK / VITB

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Laboratorios Silanes S.A. de C.V.
• Investigators: Principal Investigator: Lourdes Garza Ocaña, M.D, Department of Pharmacology and Toxicology of the Faculty of Medicine of the U.A.N.L; Principal Investigator: Eduardo J Tamez de la O, M.D, Department of Pharmacology and Toxicology of the Faculty of Medicine of the U.A.N.L

Publications and helpful links

General Publications

• Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.
• Barbanoj MJ, Gich I, Artigas R, Tost D, Moros C, Antonijoan RM, García ML, Mauleón D. Pharmacokinetics of Dexketoprofen Trometamol in Healthy Volunteers After Single and Repeated Oral Doses. J Clin Pharmacol. 1998 Dec;38(S1):33S-40S. doi: 10.1002/jcph.1998.38.s1.33.
• Barbanoj MJ, Antonijoan RM, Gich I. Clinical pharmacokinetics of dexketoprofen. Clin Pharmacokinet. 2001;40(4):245-62. doi: 10.2165/00003088-200140040-00002.

Helpful Links

• Spanish Agency for Medicines and Health Products (AEMPS). Ministry of Health, Social Policy and Equality. Technical sheet Metamizole ratiopharm 575 mg hard capsules
• STADIUM. Drugs.
• Official Mexican standard that establishes the tests and procedures to demonstrate that a drug is interchangeable. Requirements to which the Authorized Third Parties that carry out the interchangeability tests must be subject.
• R Core Team (2019). R: A language and environment for statistical computing.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2019
• Primary Completion (Actual): November 15, 2019
• Study Completion (Actual): December 2, 2019

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 30, 2021

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Bioequivalence; Bioavailability; Pharmacokinetic; Thiamine; Fixed-dose combination (FDC); Dexketoprofen; Trometamol; Cyanocobalamin; Pyridoxine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex; Dexketoprofen trometamol
• Other Study ID Numbers: DEXK-Sil No. 101-18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No