Analgesic Effect of Different Combinations of Dexketoprofen Trometamol With Tramadol Hydrochloride in a Model of Moderate to Severe Pain

Pain Clinical Trial

— DEX-TRA 02  

Official title:

Double-blind, Randomised, Placebo and Active Controlled, Parallel Group Study to Evaluate the Analgesic Effect of a Single Oral Administration of Four Different Combination Doses of DKP.TRIS With TRAM.HCL in Comparison With the Single Agents, on Moderate to Severe Pain Following Impacted Third Mandibular Molar Tooth Extraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01307020
• Other study ID #: DEX-TRA 02
• Secondary ID: 2010-022798-32
• Status: Completed
• Phase: Phase 2
• First received: February 28, 2011
• Last updated: July 31, 2013
• Start date: February 2011
• Est. completion date: October 2011

Study information

• Verified date: July 2013
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesHungary: Research Ethics Medical CommitteeItaly: Ethics CommitteePoland: Ministry of HealthSpain: Ministry of HealthUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the analgesic efficacy of Dexketoprofen Trometamol and Tramadol Hydrochloride given in combinations and the analgesic efficacy of each single component in comparison to placebo on moderate to severe pain following impacted third mandibular molar tooth extraction. Ibuprofen will be used as an active control to validate the pain model.

Description:

The aim of this study is to develop a combination of Dexketoprofen Trometamol (DKP.TRIS) and Tramadol Hydrochloride (TRAM.HCl) for the treatment of acute moderate to severe pain, based on the rationale that more than one drug is necessary in most patients suffering of acute and chronic pain, particularly of moderate to severe intensity.

DKP.TRIS and TRAM.HCl have different mechanisms of action, therefore their combination is expect to result in an additive or synergistic analgesia, thus allowing a decrease in the required doses of the individual agents, and consequently a reduced risk of adverse events In this study, patients who present moderate to severe pain after impacted third mandibular molar tooth extraction will be randomised to a total of 10 treatment arms including 4 combinations of DKP.TRIS + TRAM.HCl, the four corresponding single treatments, placebo and ibuprofen. Treatment administration will be followed by a 24-hour pain and analgesic effect assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 745
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

Patients meeting ALL the following criteria will be eligible for entry into the study:

• Male or female patients aged 18 to 70 years old. Females participating in the study must be either: of non-childbearing potential, or willing to use a highly effective contraceptive method.

• Scheduled for outpatient surgical extraction -under local anaesthesia- of third mandibular molar teeth, with at least one of which is fully or partially impacted in the mandible requiring bone manipulation.

• Normal physical examination or without clinically relevant abnormalities.

At randomisation (after surgery):

No intake of analgesics (including prescription and over the counter drugs) within 24h prior to the surgery.

• No complication during the surgery, duration of surgery < 1 hour and not requiring re-anaesthesia.

• Patients experiencing pain of moderate or higher intensity in the first four hours after the end of surgery.

Exclusion Criteria:

• History of allergy or hypersensitivity to NSAIDs, opioids or acetyl salicylic acid.

• History of asthma, bronchospasm, acute rhinitis, nasal polyps, urticaria or angioneurotic oedema.

• History of peptic ulcer, gastrointestinal disorders by NSAIDs, gastrointestinal bleeding or other active bleedings.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Dexketoprofen Trometamol
Dexketoprofen Trometamol low dose, oral film-coated table, once
• Dexketoprofen Trometamol
Dexketoprofen Trometamol high dose, oral film-coated table, once
• Tramadol Hydrochloride
Tramadol Hydrochloride low dose, oral film-coated table, once
• Tramadol Hydrochloride
Tramadol Hydrochloride high dose, oral film-coated table, once
• Ibuprofen
Ibuprofen 400 mg, oral film-coated table, once
• Placebo
Placebo, oral film-coated table, once
• Dexketoprofen Trometamol + Tramadol Hydrochloride
DKP-TRIS low dose - TRAM.HCl low dose, oral film-coated table, once
• Dexketoprofen Trometamol + Tramadol Hydrochloride
DKP-TRIS low dose - TRAM.HCl high dose, oral film-coated table, once
• Dexketoprofen Trometamol + Tramadol Hydrochloride
DKP-TRIS high dose - TRAM.HCl low dose, oral film-coated tablet, once
• Dexketoprofen Trometamol + Tramadol Hydrochloride
DKP-TRIS high dose - TRAM.HCl high dose, oral film-coated tablet, once

Locations

Country	Name	City	State
Germany	Klinik und Polickinik für Mund-Kiefer-Gesichtschirurgie/Plastische Operationen Greifswald	Greifswald	Mecklenburg-Vorpommern
Germany	Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Schleswig Holstein, Campus Kiel	Kiel	Schleswig-Holstein
Hungary	Dr Tóth Bagi Zoltán Fogászati Rendeloje	Budapest
Italy	Centro di Farmacologia Clinica per la Sperimentazione dei Farmaci	Pisa
Italy	Centro di Ricerche Cliniche di Verona Srl. Policlinico G.B.Rossi	Verona
Poland	Gabinet Stomatologiczny Andrzej Wojtowicz AW Clinic	Warsaw	Mazowieckie
Poland	Dental Service spólka jawna	Warszawa	Mazowieckie
Spain	Facultad de Odontología. Departamento de Cirugía Bucal y Maxilofacial, University of Barcelona - Bellvitge Institute for Biomedical Research (IDIBELL)	L'Hospitalet de Llobregat	Barcelona
Spain	Universidad Complutense de Madrid	Madrid
Spain	Hospital Médico Quirúrgico de Conxo	Santiago de Compostela	A Coruña
Spain	Departamento de Estomatología, Facultad de Odontología. Universidad de Sevilla	Sevilla
Spain	Departament d'Estomatologia, Clínica Odontològica, Universidad de Valencia - Fundació Lluís Alcanyís	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
United Kingdom	The School of Dentistry, College of Medical and Dental Sciences, University of Birmingham	Birmingham	England
United Kingdom	University Dental Hospital	Cardiff	Wales
United Kingdom	University Dental School Manchester	Manchester	England

Sponsors (2)

Lead Sponsor	Collaborator
Menarini Group	PRA Health Sciences

Countries where clinical trial is conducted

Germany,  Hungary,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 6 Hours Post-dosing.	Pain relief is measured by a verbal rating scale (ranging from 0=none to 4=complete). Theoretical maximum TOTPAR at 6 hours is calculated by summing up the maximum score of analgesia which the patient can attribute at defined time points along 6 hour (maxTOTPAR6h= 24). Unit of measure is %	6 hours	No
Secondary	Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 4, 8 and 12 Hours Post-dosing.	Pain relief is measured by a verbal rating scale (ranging from 0=none to 4=complete). Theoretical maximum TOTPAR at 6 hours is calculated by summing up the maximum score of analgesia which the patient can attribute at defined time points along 4, 8 and 12 hours(maxTOTPAR4h= 16, maxTOTPAR8h= 32 and maxTOTPAR12h= 48, respectively) Unit of measure is %	4, 8 and 12 hours	No
Secondary	Percentage of Patients Using Rescue Medication at 6 Hours	Percentage of patients using rescue medication at 6 hours post-dosing.	Baseline to 6 hours	No