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

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

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.

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.

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.