Analgesic Effect of Different Combinations of Dexketoprofen Trometamol With Tramadol Hydrochloride in a Model of Moderate to Severe Pain (DEX-TRA 02)

This study has been completed.
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
Menarini Group
ClinicalTrials.gov Identifier:
NCT01307020
First received: February 28, 2011
Last updated: July 31, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Pain
Drug: Dexketoprofen Trometamol
Drug: Tramadol Hydrochloride
Drug: Ibuprofen
Drug: Placebo
Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Menarini Group:

Primary Outcome Measures:
  • Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 6 Hours Post-dosing. [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    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 %


Secondary Outcome Measures:
  • Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 4, 8 and 12 Hours Post-dosing. [ Time Frame: 4, 8 and 12 hours ] [ Designated as safety issue: No ]
    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 %

  • Percentage of Patients Using Rescue Medication at 6 Hours [ Time Frame: Baseline to 6 hours ] [ Designated as safety issue: No ]
    Percentage of patients using rescue medication at 6 hours post-dosing.


Enrollment: 745
Study Start Date: February 2011
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo, oral film-coated table, once
Active Comparator: Ibuprofen Drug: Ibuprofen
Ibuprofen 400 mg, oral film-coated table, once
Active Comparator: TRAM.HCl high dose Drug: Tramadol Hydrochloride
Tramadol Hydrochloride high dose, oral film-coated table, once
Active Comparator: TRAM.HCl low dose Drug: Tramadol Hydrochloride
Tramadol Hydrochloride low dose, oral film-coated table, once
Active Comparator: DKP-TRIS high dose Drug: Dexketoprofen Trometamol
Dexketoprofen Trometamol high dose, oral film-coated table, once
Active Comparator: DKP-TRIS low dose Drug: Dexketoprofen Trometamol
Dexketoprofen Trometamol low dose, oral film-coated table, once
Experimental: DKP-TRIS low dose - TRAM.HCl low dose Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride
DKP-TRIS low dose - TRAM.HCl low dose, oral film-coated table, once
Experimental: DKP-TRIS low dose - TRAM.HCl high dose Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride
DKP-TRIS low dose - TRAM.HCl high dose, oral film-coated table, once
Experimental: DKP-TRIS high dose - TRAM.HCl low dose Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride
DKP-TRIS high dose - TRAM.HCl low dose, oral film-coated tablet, once
Experimental: DKP-TRIS high dose - TRAM.HCl high dose Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride
DKP-TRIS high dose - TRAM.HCl high dose, oral film-coated tablet, once

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307020

Locations
Germany
Klinik und Polickinik für Mund-Kiefer-Gesichtschirurgie/Plastische Operationen Greifswald
Greifswald, Mecklenburg-Vorpommern, Germany, 17475
Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Schleswig Holstein, Campus Kiel
Kiel, Schleswig-Holstein, Germany, 24105
Hungary
Dr Tóth Bagi Zoltán Fogászati Rendeloje
Budapest, Hungary, 1052
Italy
Centro di Farmacologia Clinica per la Sperimentazione dei Farmaci
Pisa, Italy, 56126
Centro di Ricerche Cliniche di Verona Srl. Policlinico G.B.Rossi
Verona, Italy, 37134
Poland
Gabinet Stomatologiczny Andrzej Wojtowicz AW Clinic
Warsaw, Mazowieckie, Poland, 00-852
Dental Service spólka jawna
Warszawa, Mazowieckie, Poland, 02-791
Spain
Hospital Médico Quirúrgico de Conxo
Santiago de Compostela, A Coruña, Spain, 15706
Facultad de Odontología. Departamento de Cirugía Bucal y Maxilofacial, University of Barcelona - Bellvitge Institute for Biomedical Research (IDIBELL)
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Universidad Complutense de Madrid
Madrid, Spain, 28040
Departamento de Estomatología, Facultad de Odontología. Universidad de Sevilla
Sevilla, Spain, 41009
Departament d'Estomatologia, Clínica Odontològica, Universidad de Valencia - Fundació Lluís Alcanyís
Valencia, Spain, 046010
Hospital General Universitario de Valencia
Valencia, Spain, 46014
United Kingdom
The School of Dentistry, College of Medical and Dental Sciences, University of Birmingham
Birmingham, England, United Kingdom, B4 6 NN
University Dental School Manchester
Manchester, England, United Kingdom, M15 6FH
University Dental Hospital
Cardiff, Wales, United Kingdom, CF14 4 XY
Sponsors and Collaborators
Menarini Group
PRA Health Sciences
Investigators
Study Chair: Cosme Gay-Escoda, Professor Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Barcelona - Bellvitge Institute for Biomedical Research (IDIBELL) 08907 Hospitalet de Llobregat, Barcelona (Spain)
Study Chair: R Andrew Moore, Professor Pain Research & Nuffield Division of Anaesthesics, Department of Clinical Neurosciences, University of Oxford. The Churchill, Oxford OX3 7LJ (United Kingdom)
  More Information

No publications provided

Responsible Party: Menarini Group
ClinicalTrials.gov Identifier: NCT01307020     History of Changes
Other Study ID Numbers: DEX-TRA 02, 2010-022798-32
Study First Received: February 28, 2011
Results First Received: October 11, 2012
Last Updated: July 31, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Hungary: Research Ethics Medical Committee
Italy: Ethics Committee
Poland: Ministry of Health
Spain: Ministry of Health
United Kingdom: Research Ethics Committee

Keywords provided by Menarini Group:
Moderate to severe pain
Postoperative pain
Analgesics
Dexketoprofen
Tramadol

Additional relevant MeSH terms:
Analgesics
Dexketoprofen trometamol
Ibuprofen
Ketoprofen
Tramadol
Analgesics, Non-Narcotic
Analgesics, Opioid
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Central Nervous System Depressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014