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

NCT05533073 | Completed Phase 1

• 1 other identifier: BD ET-Sil No. 112-19
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Pharmacokinetic; Bioavailability; Fixed-dose combination (FDC); Etoricoxib; Tramadol; Pain

Outcome Measures

Primary Outcomes (6)

• Maximum observed concentration following the treatment (Cmax)

  Evaluate the pharmacokinetics profile of the fixed dose Etoricoxib/Tramadol, employing the maximum observed concentration following the treatment (Cmax), obtained graphically, from the plasma concentration profile with respect to time.

  Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours.

• The area under the curve from time zero to the last measurable concentration (AUC 0-t)

  Evaluate the fixed dose pharmacokinetics profile of Etoricoxib/Tramadol, employing the area under the curve from time zero to the last measurable concentration (AUC 0-t) using the linear trapezoidal method.

  Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours.

• The area under the curve from time zero to infinity calculated (AUC 0-inf),

  Evaluate the fixed dose pharmacokinetics profile of Etoricoxib/Tramadol, employing the area under the curve from time zero to infinity calculated (AUC 0-inf).

  Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours.

• Time of the maximum measured concentration (Tmax).

  Evaluate the fixed dose pharmacokinetics profile of Etoricoxib/Tramadol, employing time of the maximum measured concentration (tmax), Obtained graphically, from the plasma concentration profile with respect to time.

  Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours.

• Elimination rate (Ke)

  Evaluate the fixed dose pharmacokinetics profile of Etoricoxib/Tramadol, employing the elimination rate (Ke), estimated from the terminal linear portion of the plasma concentration profile with respect to time (on a semi-log scale)

  Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours.

• Half time elimination (t1/2)

  Evaluate the pharmacokinetics profile of the fixed dose Etoricoxib/Tramadol, employing the half time elimination (t1/2) by the quotient of Ln(2)Ke.

  Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours.

Secondary Outcomes (2)

• Determine the frequency of occurrence of adverse events

  1, 15 and 29 days

• Adverse Events

  1, 15 and 29 days

Study Arms (3)

Group A: Etoricoxib/Tramadol FDC

EXPERIMENTAL

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

Drug: A1: Etoricoxib / Tramadol Fixed dose combination

Group B: Etoricoxib

ACTIVE COMPARATOR

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

Drug: A2: Etoricoxib

Group C: Tramadol

ACTIVE COMPARATOR

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

Drug: A3: Tramadol

Interventions

A1: Etoricoxib / Tramadol Fixed dose combination 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

Also known as: E/T

Group A: Etoricoxib/Tramadol FDC

A2: Etoricoxib 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

Also known as: Arcoxia®

Group B: Etoricoxib

A3: Tramadol DRUG

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

Also known as: Tradol®

Group C: Tramadol

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laboratorios Silanes S.A. de C.V.: lead

Study Sites (1)

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

Mexico City, 11000, Mexico

Location

Related Publications (6)

• 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.

  PMID: 5650254 BACKGROUND

• 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.

  PMID: 3450848 BACKGROUND

• 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.

  PMID: 6747820 BACKGROUND

• 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.

  PMID: 22232850 BACKGROUND

• 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.

  PMID: 12638395 BACKGROUND

• 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.

  PMID: 20435245 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

Tramadol; Etoricoxib

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids; Sulfones; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lourdes Garza Ocaña, M.D

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 8, 2022
• Study Start: August 3, 2020
• Primary Completion: September 7, 2020
• Study Completion: November 30, 2020
• Last Updated: September 9, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)