Paracetamol UNIFLASH for Buccal Use Phase III Trial in Acute Pain Due to a Tooth Extraction

Study Overview
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Brief Summary
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This study aims to evaluate the analgesic efficacy of single dose of a new paracetamol formulation (paracetamol UNIFLASH) for buccal use in comparison to two different doses of an oral paracetamol form controlled versus placebo.

Official Title
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Comparison of the Analgesic Effect of a New Paracetamol Formulation (Paracetamol UNIFLASH) for Buccal Use and Two Different Doses of an Oral Paracetamol Form Controlled Versus Placebo in Patients Suffering From Moderate Pain Due to a Tooth Extraction.

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: Paracetamol Uniflash 125mg
* Drug: Panadol 500 MG Oral Tablet X1
* Drug: Panadol 500 MG Oral Tablet X2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged from 18 years of age Patients scheduled to undergo the removal of one third soft-tissue impacted or not-impacted mandibular molar (associated or not to an ipsilateral erupted maxillary molar) under short-acting local anaesthetic preoperatively; Patients weighing > 50 kg; Additional inclusion criteria Patients experiencing a moderate pain within 4 hours after the dental extraction, defined by a baseline pain intensity Visual Analogic Scale (VAS) score ≥ 40 mm and ≤ 60 mm; Third mandibular molar extraction completed without any immediate complication, that in the opinion of the investigator, would interfere with the study conduct and/or assessments (e.g., suspected neurosensory complication, incomplete removal of tooth). Exclusion Criteria: Patient who undergoes an extraction of contralateral molar in the same procedure or a bony-impacted molar; Patients treated by analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) within the 3 days prior to the day of randomization (or within 5 times the elimination half-life whichever the longest); Patient who received other analgesic than short-acting preoperative or intraoperative local anaesthetic agents within 12 hours before the start of the surgery or peri-operatively until randomization; Patients with any known hypersensitivity to paracetamol, ibuprofen or ingredients contained in IMPs and Non-Investigational Medicinal Product (NIMP);

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol UNIFLASH 125mg<br>1 sachet Paracetamol UNIFLASH 125mg + 2 placebo capsule | Drug: Paracetamol Uniflash 125mg<br>* Oromucosal solution 1.25 mL for buccal use<br>Drug: Placebo<br>* Dummy treatment<br>|
| Placebo Comparator: Placebo<br>1 Placebo sachet + 2 placebo capsule | Drug: Placebo<br>* Dummy treatment<br>|
| Active Comparator: Paracetamol 500mg<br>1 Placebo sachet + 1 placebo capsule + 1 capsule Panadol 500mg | Drug: Panadol 500 MG Oral Tablet X1<br>* Tablet masked in capsule<br>Drug: Placebo<br>* Dummy treatment<br>|
| Active Comparator: Paracetamol 1000mg<br>1 Placebo sachet + 2 capsules Panadol 500mg | Drug: Panadol 500 MG Oral Tablet X2<br>* Tablet masked in capsule<br>Drug: Placebo<br>* Dummy treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ranked Efficacy Endpoints: 1. Sum of Pain Intensity Difference (SPID0-60min) | Pain Intensity Difference will be calculated using the scores of pain intensity assessed by the patient at defined time-points (T5, T10, T15, T20, T30, T45, T60 min) after the IMP intake and/or right before first intake of rescue medication using a 100-mm Visual Analogic Scale (0= no pain and 100= worst imaginable pain) compared to baseline | At 60 minutes | 
| Onset of pain relief (versus 500 mg of the reference oral paracetamol (Panadol®) | Defined as the period for the patient to reach a meaningful pain relief during the first 60 min post-IMP intake. After completion of the 5-point verbal rating scale (VRS) at T5, T10, T15, T20, T30, T45, T60 min post-IMP intake assessment time points, the patient will have to answer this question Do you consider this level of pain relief as meaningful - Yes or No? | At 60 minutes | 
| Proportion of responder patients at 60 minutes (versus 500 mg of the reference oral paracetamol (Panadol®)). | A responder patient is defined as a subject who achieves a reduction of 50 % of pain intensity compared to baseline. | At 60 minutes | 
| Patient Global Impression of Change (PGIC) versus 1000 mg of the reference oral paracetamol (Panadol®) |  | At 60 minutes | 
| Onset of pain relief (versus 1000 mg of the reference oral paracetamol (Panadol®)). | Defined as the period for the patient to reach a meaningful pain relief during the first 60 min post-IMP intake. After completion of the a 5-point verbal rating scale at T5, T10, T15, T20, T30, T45, T60 min post-IMP intake assessment time points, the patient will have to answer this question Do you consider this level of pain relief as meaningful - Yes or No? | At 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Difference at 5 minutes (SPID0-5min), 10 minutes (SPID0-10min), 30 minutes (SPID0-30min), 45 minutes (SPID0-45min), 1 hour (SPID0-1h), 2 hours (SPID0-2h), 4 hours (SPID0-4h), and 6 hours (SPID0-6h). | Pain Intensity Difference will be calculated using the score of pain intensity assessed by the patient at defined time-points (T5, T10, T15, T20, T30, T45, T90, T120, T180, T240, T300 and T360 min) after IMP intake or right before first intake of rescue medication using a 100-mm Visual Analogic Scale compared to baseline. | At 5 minutes, 10 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, and 6 hours. | 
| Proportion of responders at 60 minutes (versus 1000 mg of the reference oral paracetamol (Panadol®)). | A responder patient is defined as a subject who achieves a reduction of 50 % of pain intensity compared to baseline. | At 60 minutes | 
| Proportion of responders at 5 minutes, 10 minutes, 30 minutes, 45 minutes, 2 hours, 4 hours and then 6 hours. | A responder patient is defined as a subject who achieves a reduction of 50 % of pain intensity compared to baseline at each time point of the study. | At 5 minutes, 10 minutes, 30 minutes, 45 minutes, 2 hours, 4 hours and then 6 hours. | 
| Total Pain Relief at 1 hour (TOTPAR0-1h), 2 hours (TOTPAR0-2h), 4 hours (TOTPAR0-4h) and 6 hours (TOTPAR0-6h) | Pain relief (PAR) will be assessed by the patient at defined time points (T5, T10, T15, T20, T30, T45, T60, T90, T120, T180, T240, T300 and T360 min) after IMP intake and/or right before first intake of rescue medication using a 5-point verbal rating scale. | At 1 hour, 2 hours, 4 hours and 6 hours. | 
| Period of time before taking rescue analgesic treatment intake. |  | Up to 24 hours after dose | 
| Proportion of patients taking a rescue analgesic treatment. |  | At 6 hours | 
| Patient Global Impression of Change (PGIC) versus 500 mg of the reference oral paracetamol (Panadol®) |  | At 60 minutes | 
| Patient Global Impression of Change (PGIC) versus 500 mg and 1000 mg of the reference oral paracetamol (Panadol®) |  | At 360 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paracetamol