Pharmacokinetic Non-interaction Study With a Fixed-dose Combination Tablet With Tramadol and Diclofenac

NCT03766984 | Completed Phase 1

• 2 other identifiers: DCLF/TRMD-GRNN-01HP8001-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study was to evaluate whether or not there is a substantial pharmacokinetic interaction between diclofenac and tramadol in a new formulation of a fixed-dose combination of diclofenac 25 milligrams (mg) and tramadol 25 mg for oral administration. The study was conducted in healthy participants of both genders.

Conditions

Pharmacokinetics

Keywords

fixed-dose combination; diclofenac; tramadol; interaction

Outcome Measures

Primary Outcomes (4)

• Maximum plasma concentration (Cmax) of diclofenac

  16 plasma samples were collected from pre-dose to 36 hours post-dose. Diclofenac concentrations were determined using validated analytical methods.

  From pre-dose to 36 hours post-dose

• Maximum plasma concentration (Cmax) of tramadol

  16 plasma samples were collected from pre-dose to 36 hours post-dose. Tramadol concentrations were determined using validated analytical methods.

  From pre-dose to 36 hours post-dose

• Area under the plasma concentration curve from the administration until the time t (AUC0-t) of diclofenac

  16 plasma samples were collected from pre-dose to 36 hours post-dose. Diclofenac concentrations were determined using validated analytical methods.

  From pre-dose to 36 hours post-dose

• Area under the plasma concentration curve from the administration until the time t (AUC0-t) of tramadol

  16 plasma samples were collected from pre-dose to 36 hours post-dose. Tramadol concentrations were determined using validated analytical methods.

  From pre-dose to 36 hours post-dose

Secondary Outcomes (14)

• Maximum plasma concentration (Cmax) of tramadol metabolite M1

  From pre-dose to 36 hours post-dose

• Area under the plasma concentration curve from the administration until the time t (AUC0-t) of tramadol metabolite M1

  From pre-dose to 36 hours post-dose

• Area under the plasma concentration curve from 0 to infinity (AUC0-inf) of tramadol

  From pre-dose to 36 hours post-dose

• Area under the plasma concentration curve from 0 to infinity (AUC0-inf) of tramadol metabolite M1

  From pre-dose to 36 hours post-dose

• Area under the plasma concentration curve from 0 to infinity (AUC0-inf) of diclofenac

  From pre-dose to 36 hours post-dose

Study Arms (3)

Diclofenac 25 mg

EXPERIMENTAL

Participants receive 1 tablet of diclofenac sodium 25 mg with 250 milliliters of purified water.

Drug: Diclofenac sodium 25 mg

Tramadol 25 mg

EXPERIMENTAL

Participants receive 1 tablet of tramadol hydrochloride 25 mg with 250 milliliters of purified water.

Drug: Tramadol hydrochloride 25 mg

Diclofenac/Tramadol 25 mg/25 mg FDC

EXPERIMENTAL

Participants receive 1 fixed-dose combination tablet of diclofenac sodium 25 mg/tramadol hydrochloride 25 mg with 250 milliliters of purified water.

Drug: Diclofenac sodium 25 mg/Tramadol hydrochloride 25 mg

Interventions

Diclofenac sodium 25 mg DRUG

Diclofenac sodium 25 mg Tablets (Laboratorios Tecnandina S.A., Ecuador)

Diclofenac 25 mg

Tramadol hydrochloride 25 mg DRUG

Tramadol hydrochloride 25 mg Tablets (Laboratorios Tecnandina S.A., Ecuador)

Tramadol 25 mg

Diclofenac sodium 25 mg/Tramadol hydrochloride 25 mg DRUG

Fixed-dose combination tablet containing diclofenac sodium 25 mg and tramadol hydrochloride 25 mg (Laboratorios Tecnandina S.A., Ecuador)

Also known as: Adorlan (Trade Mark)

Diclofenac/Tramadol 25 mg/25 mg FDC

Eligibility Criteria

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

You may qualify if:

• Man or woman between 18 and 55 years of age.
• Women with use of a barrier method as a contraceptive.
• Body mass index equal to or above 18.0 and equal to or less than 27.0 kilograms per square meter.
• Clinically healthy. If the clinical history, the registration of vital signs and the physical examination did not show abnormal deviations that avoid their participation in a clinical study.
• Without a history of allergic reactions to the study drug.
• Stable vital signs during the selection (heart rate, respiratory rate, blood pressure at rest and axillary body temperature).
• Electrocardiogram (ECG) with no pathological alterations, with validity of no more than 3 months.
• The participant accepts the restrictions and indications described in the protocol and internal regulations.

You may not qualify if:

• Findings in the clinical history, vital signs and/or physical examination that show abnormal conditions of the general state of health of the participant that avoid its participation in a clinical study.
• Recent exposure to the study drug between the 30 days prior or any other medication by prescription or self consumed between the 14 days prior to the start of the study, or that do not accept to avoid its consumption during the course of the study.
• Surgery during the 30 days prior to the start of the study.
• Suspicion or evidence of infection by Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV).
• Serologic test for syphilis (Venereal Disease Research Laboratory test) positive.
• Known hypersensitivity to any medication.
• Blood donation equal to or above 1 unit (0.5 liters) during the 30 days prior to the selection.
• Participants who have special food requirements or food restrictions.
• Women in the breastfeeding period and/or pregnant.
• Positive results in the qualitative test of pregnancy in urine (only women).
• Positive result in the qualitative detection of drugs of abuse.
• Participation in a clinical study Phase 1, 2 or 3 or bioavailability/ bioequivalence studies during the 3 months previous to the selection.
• The participant does not give his or her authorization to participate in the study through the signing of an informed consent, or is not willing to follow the indications and/or restrictions of the protocol and rules of the procedure.
• The participant is vulnerable or potentially vulnerable by which cannot freely express his/her consent by subordination of the principal investigator or by coercion of any third party.

Sponsors & Collaborators

• Grünenthal GmbH: lead
• Grünenthal Colombiana S.A.: collaborator

Study Sites (1)

Clinical Unit of Biodextra, S.A. de C.V.

Mexico City, CP 09360, Mexico

Location

MeSH Terms

Interventions

Diclofenac; Tramadol

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Amines; Lipids

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

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

Model Details: Longitudinal, prospective, crossover, open, randomized, single-dose study with 3 periods, 2 sequences (ACB and BCA), and 3 treatments (A, B, and C) in healthy participants and under fasting conditions.

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 6, 2018
• Study Start: June 7, 2015
• Primary Completion: June 23, 2015
• Study Completion: June 23, 2015
• Last Updated: December 11, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

ME (1)