Comparative Bioavailability Study Between Etoricoxib and Tramadol, Administered Individually or in Combination

NCT ID: NCT05533073

Last Updated: 2022-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-03
• Study Completion Date: 2020-11-30

Brief Summary

Study carried out in the Clinical and Analytical Unit of the Department of Pharmacology and Toxicology of the Faculty of Medicine of the Autonomous University of Nuevo León, with the objective of comparing the bioavailability (Cmax, AUC) of an oral formulation containing Etoricoxib 90 mg / Tramadol 50 mg in combination with that of two oral formulations, Etoricoxib 90 mg or Tramadol 50 mg, administered as a single dose, in healthy subjects under fasting conditions.

Detailed Description

The study design was a crossover, 3 x 6 x 3, open-label, prospective and longitudinal, truncated, single-dose combination of Etoricoxib 90 mg / Tramadol 50 mg administered orally versus each component administered individually, with three treatments, three periods. , six sequences with an elimination period (washout) of 14 days and with a total of 42 healthy subjects, of both genders, under fasting conditions. Among the objectives were the characterization of the pharmacokinetic parameters, Cmax, AUC 0-72, Tmax, Ke and T1/2 of Etoricoxib and Tramadol after oral administration in a single dose, in combination: sachet with granules equivalent to Etoricoxib 90 mg/ Tramadol 50 mg manufactured by Laboratorios Silanes, S.A. of C.V. versus each component administered individually: Etoricoxib 90 mg tablet (Arcoxia®) manufactured by Schering Plough S.A de C.V. and Tramadol 50 mg capsule (Tradol®) made by Grunenthal GMBH (private company).

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A: Etoricoxib/Tramadol FDC

Pharmaceutical Form: Sachet with granules to dilute in 100 mL of water Formula: Each sachet contains Etoricoxib 90 mg / Tramadol 50 mg Dosage: 100 mL Administration way: oral

Group Type: EXPERIMENTAL

A1: Etoricoxib / Tramadol Fixed dose combination

Intervention Type: DRUG

Sachet with granules (Laboratorios Silanes S.A. de C.V.). Formula : 90 mg/ 50 mg Pharmaceutical Form: Sachet with granules Dosage: 100 mL (90 mg/ 50mg) Administration way: oral

Group B: Etoricoxib

Pharmaceutical Form: Tablet Formula: Tablet containing Etoricoxib 90 mg Dosage: 1 tablet of 90 mg Administration way: oral

Group Type: ACTIVE_COMPARATOR

A2: Etoricoxib

Intervention Type: DRUG

Arcoxia®, Schering Plough S.A. de C.V. A2: Pharmaceutical Form: Tablet Formula: 90 mg Dosage: 1 tablet of 90 mg Administration way: oral

Group C: Tramadol

Pharmaceutical Form: Capsule Formula: Each capsule contains 50mg of Tramadol Dosage:1 capsule of 50 mg Administration way: oral

Group Type: ACTIVE_COMPARATOR

A3: Tramadol

Intervention Type: DRUG

Tradol®, from Grünenthal GMBH. Pharmaceutical Form: Capsule Formula: Each capsule contains 50 mg Dosage: 1 capsule of 50 mg Administration way: oral

Interventions

A1: Etoricoxib / Tramadol Fixed dose combination

Sachet with granules (Laboratorios Silanes S.A. de C.V.). Formula : 90 mg/ 50 mg Pharmaceutical Form: Sachet with granules Dosage: 100 mL (90 mg/ 50mg) Administration way: oral

Intervention Type: DRUG

A2: Etoricoxib

Arcoxia®, Schering Plough S.A. de C.V. A2: Pharmaceutical Form: Tablet Formula: 90 mg Dosage: 1 tablet of 90 mg Administration way: oral

Intervention Type: DRUG

A3: Tramadol

Tradol®, from Grünenthal GMBH. Pharmaceutical Form: Capsule Formula: Each capsule contains 50 mg Dosage: 1 capsule of 50 mg Administration way: oral

Intervention Type: DRUG

Other Intervention Names

E/T; Arcoxia®; Tradol®

Eligibility Criteria

Inclusion Criteria

• The subjects must have been accepted by the COFEPRIS (Federal Commission for the Protection against Sanitary Risks) research subjects registration database.
• Subjects without a subordinate relationship with the researchers.
• Subjects who have given informed consent in writing.
• Subjects of both genders, aged between 18 and 55 years, Mexicans. - -Subjects with no background of hypersensitivity or allergies to the drug under study or related drugs.
• 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 analyses, carried out in certified clinical laboratories, without alterations that require a medical intervention as a consequence.
• Subjects with negative results for immunological tests (Anti-HIV, Anti-hepatitis B and C, VDRL).
• Subjects with negative results in drug abuse screening tests: tetrahydrocannabinoids, cocaine and amphetamines.
• Negative (qualitative) pregnancy test for women of childbearing potential without Bilateral tubal obstruction or hysterectomy.
• In the case of women of childbearing age, they must have a birth control method, including barrier methods, non-hormonal intrauterine device, or bilateral tubal obstruction.

Exclusion Criteria

• Subjects with recent history or physical examination evidence of gastrointestinal, renal, hepatic, endocrine, respiratory, cardiovascular, dermatological, or hematological disease that could affect the pharmacokinetic study of the product in research.
• Subjects who have been exposed to drugs known as liver enzyme inducers or inhibitors or who have taken drugs potentially toxic within 30 days before the start of the study.
• Subjects who have received any medication during the 7 days before the start of the study.
• Subjects who have been hospitalized for any problem during the three months before the start of the study.
• Subjects who have been rejected by the registry database of research subjects of COFEPRIS, 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 the previous 60 days th the start of the study.
• Subjects allergic to the study drug or related drugs.
• Subjects who have ingested alcohol or drinks containing xanthines (coffee, tea, cocoa, chocolate, cola) or who have eaten charcoal-grilled food or grapefruit juice , at least 10 hours before the start of the study or who have smoked tobacco 24 hours before to the start of the internment period.
• Subjects who have donated or lost 450 mL or more of blood within the previous 60 days of the beginning 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.
• Research subjects who presents alterations in the vital signs recorded during the selection.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Laboratorios Silanes S.A. de C.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lourdes Garza Ocaña, M.D

Role: PRINCIPAL_INVESTIGATOR

Department of Pharmacology and Toxicology of the Faculty of Medicine of the U.A.N.L

Locations

Laboratorio Silanes, S.A. de C.V.

Mexico City, , Mexico

Countries

Mexico

References

Rosenthal R. An application of the Kolmogorov-Smirnov test for normality with estimated mean and variance. Psychol Rep. 1968 Apr;22(2):570. doi: 10.2466/pr0.1968.22.2.570. No abstract available.

Reference Type: BACKGROUND

PMID: 5650254 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 3450848 (View on PubMed)

Hauck WW, Anderson S. A new statistical procedure for testing equivalence in two-group comparative bioavailability trials. J Pharmacokinet Biopharm. 1984 Feb;12(1):83-91. doi: 10.1007/BF01063612.

Reference Type: BACKGROUND

PMID: 6747820 (View on PubMed)

Shohag MH, Islam MS, Ahmed MU, Joti JJ, Islam MS, Hasanuzzaman M, Hasnat A. Pharmacokinetic and bioequivalence study of etoricoxib tablet in healthy Bangladeshi volunteers. Arzneimittelforschung. 2011;61(11):617-21. doi: 10.1055/s-0031-1300564.

Reference Type: BACKGROUND

PMID: 22232850 (View on PubMed)

Agrawal NG, Porras AG, Matthews CZ, Rose MJ, Woolf EJ, Musser BJ, Dynder AL, Mazina KE, Lasseter KC, Hunt TL, Schwartz JI, McCrea JB, Gottesdiener KM. Single- and multiple-dose pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, in man. J Clin Pharmacol. 2003 Mar;43(3):268-76. doi: 10.1177/0091270003251122.

Reference Type: BACKGROUND

PMID: 12638395 (View on PubMed)

Silva Mde F, Schramm SG, Kano EK, Mori Koono EE, Porta V, dos Reis Serra CH. Bioequivalence evaluation of single doses of two tramadol formulations: a randomized, open-label, two-period crossover study in healthy Brazilian volunteers. Clin Ther. 2010 Apr;32(4):758-65. doi: 10.1016/j.clinthera.2010.03.016.

Reference Type: BACKGROUND

PMID: 20435245 (View on PubMed)

Other Identifiers

BD ET-Sil No. 112-19

Identifier Type: -

Identifier Source: org_study_id