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

Menarini

Status and phase: Completed; Phase 2

Conditions: Pain

Treatments: Drug: Tramadol Hydrochloride; Drug: Ibuprofen; Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride; Drug: Placebo; Drug: Dexketoprofen Trometamol

Study type: Interventional

Funder types: Industry

Identifiers

NCT01307020

DEX-TRA 02

2010-022798-32 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 745 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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745 participants in 10 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Ibuprofen

Active Comparator group

Treatment:

Drug: Ibuprofen

TRAM.HCl high dose

Active Comparator group

Treatment:

Drug: Tramadol Hydrochloride

Drug: Tramadol Hydrochloride

TRAM.HCl low dose

Active Comparator group

Treatment:

Drug: Tramadol Hydrochloride

Drug: Tramadol Hydrochloride

DKP-TRIS high dose

Active Comparator group

Treatment:

Drug: Dexketoprofen Trometamol

Drug: Dexketoprofen Trometamol

DKP-TRIS low dose

Active Comparator group

Treatment:

Drug: Dexketoprofen Trometamol

Drug: Dexketoprofen Trometamol

DKP-TRIS low dose - TRAM.HCl low dose

Experimental group

Treatment:

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

DKP-TRIS low dose - TRAM.HCl high dose

Experimental group

Treatment:

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

DKP-TRIS high dose - TRAM.HCl low dose

Experimental group

Treatment:

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

DKP-TRIS high dose - TRAM.HCl high dose

Experimental group

Treatment:

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride

Drug: Dexketoprofen Trometamol + Tramadol Hydrochloride