Tramadol Hydrochloride and Dexketoprofen Trometamol for the Oral Treatment of Moderate to Severe Acute Pain Following Removal of Impacted Lower Third Molar

Study Overview
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Brief Summary
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The study is aimed to evaluate the analgesic efficacy of TRAM.HCl/DKP.TRIS 75mg/25mg oral fixed drug combination in comparison with TRAM.HCl /paracetamol 75mg/650mg in the treatment of moderate to severe acute pain.

Detailed Description
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The present phase IV study is a randomised, double-blind, placebo and active-controlled, parallel group study in moderate to severe acute pain after removal of impacted lower third molar. In this single-dose clinical trial patients are randomized to the following 3 treatment arms in a 2:2:1 ratio: TRAM.HCL/DKP.TRIS Paracetamol/TRAM.HCL Placebo.

Official Title
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Analgesic Efficacy of Oral Dexketoprofen Trometamol/Tramadol Hydrochloride Versus Tramadol Hydrochloride/Paracetamol: a Randomised, Double-blind, Placebo and Active-controlled, Parallel Group Study in Moderate to Severe Acute Pain After Removal of Impacted Lower Third Molar (Dexketoprofen Analgesic eVolution wIth tramaDol- DAVID Study)

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: Tramadol Hydrochloride/Dexketoprofen Trometamol
* Drug: Tramadol Hydrochloride/Paracetamol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged more than 18 years. Females participating in the study must be either non-childbearing potential or routinely using an effective method of birth control resulting in a low failure rate. Scheduled for outpatient surgical extraction -under local anaesthesia of lower third molar teeth, with at least one partially impacted in the mandible requiring bone manipulation. Pain of at least moderate intensity in the first 4 hours after the end of surgery (NRS score ≥ 4). Exclusion Criteria: History of allergy or hypersensitivity to the study treatments, RM or to any other NSAIDs, opioids and acetyl salicylic acid. History of peptic ulcer, gastrointestinal disorders by NSAIDs or gastrointestinal bleeding or other active bleedings. History of any illness or condition that, in the opinion of the Investigator might pose a risk to the patient or confound the efficacy and safety results of the study. Patients using and not suitable for withdrawing the prohibited medications specified in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tramadol/Dexketoprofen<br>Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg film-coated tablet oral single dose; Placebo matching Tramadol Hydrochloride/Paracetamol 75 mg/650mg, as 2 x [37.5mg/325mg] film-coated tablets, oral single dose. | Drug: Tramadol Hydrochloride/Dexketoprofen Trometamol<br> <br> Drug: Placebo<br> <br> |
| Active Comparator: Tramadol/Paracetamol<br>Tramadol Hydrochloride/Paracetamol 75 mg/650 mg, as 2 x [37.5mg/325mg] film-coated tablets, oral single dose; Placebo matching Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg film-coated tablet oral single dose. . | Drug: Tramadol Hydrochloride/Paracetamol<br> <br> Drug: Placebo<br> <br> |
| Placebo Comparator: Placebo<br>Placebo matching one film-coated tablet of Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg oral single dose; Placebo matching two film-coated tablets of Tramadol Hydrochloride/Paracetamol 37.5mg/325mg oral single dose. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TOTPAR6 (Total Pain Relief Over 6 Hours Post-dose) | TOTPAR calculated as the weighted sum of the PAR scores, measured according to a 5-point VRS (Verbal Rating Scale) from 0=no relief to 4=complete relief, over 6 hours post-dose (TOTPAR6). The TOTPAR6 ranges from a minimum of 0 to a maximum of 24. | 6 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of Patients Achieving 50% of Max TOTPAR | Percentage of patients who achieved at least 50% of the maximum TOTPAR at 8 hours. In the present trial the achievable TOTPAR over 8 hours ranges between 0 and 32. | 8 hours post-dose | 
| % of Patients Achieving at Least 30% of PI (Pain Intensity) Reduction Over 8 Hours Post-dose | Percentage of patients who achieve at least 30% of PI Reduction versus baseline Over 8 Hours Post-dose. Percentage change of PI is calculated using the baseline value minus the PI assessed at 8 hours post-dose divided for the baseline value, then multiplied for 100. | 8 hours post-dose | 
| Time to Confirmed FPPAR (First Perceptible Pain Relief) | Time to confirmed FPPAR (time to onset of analgesia) - i.e. time to FPPAR if confirmed by experiencing Meaningful Pain Relief (MPAR) FPPAR and MPAR assessed by using stopwatches: 'first perceptible' PAR (FPPAR), i.e, at the moment they first felt any PAR whatsoever; 'meaningful' PAR (MPAR, ie, when the relief from pain became meaningful to them) | 2 hours post-dose | 
| % of Patients Requiring RM (Rescue Medication) | Percentage of patients who required RM within the first over 8 hours post-dose. | 8 hours post-dose | 
| PGE (Patient Global Evaluation) | PGE of the study medication (measured according to a five-point VRS from 1 = poor to 5 = excellent) at 8 hours post-dose or whenever the patient uses Rescue Medication (RM). | 8 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute pain, Acute moderate to severe pain, Postoperative pain, Dexketoprofen Tramadol, Dexketoprofen trometamol, Tramadol hydrochloride, Multimodal analgesia, Third molar extraction, Fixed drug combination, Paracetamol, Analgesics