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

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.

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.

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Paracetamol Uniflash 125mg; Drug: Placebo; Drug: Panadol 500 MG Oral Tablet X1; Drug: Panadol 500 MG Oral Tablet X2

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33075
    • CHU de Bordeaux
  • Clermont Ferrand, France, 63003
    • CHRU de Clermont Ferrand
  • Colombes, France, 92700
    • Hopital Louis Mourier
  • Montpellier, France, 34070
    • CHU Montpellier
  • Strasbourg, France
    • CHU de Strasbourg
• Italy
  • Milano, Italy
    • Universita degli Studi di Milano
  • Udine, Italy
    • Department of maxilla facial Surgery -University of Udine
• Poland
  • Gdansk, Poland
    • University Central Stomatology GDANSK
  • Lodz, Poland, 92213
    • Oral Surgery Department, Central Clinical Hospital
  • Lodz, Poland
    • Dental practice
  • Lublin, Poland
    • Oral surgery Medical University of Lublin
  • Warszawa, Poland
    • AW Clinic
  • Wroclaw, Poland, 50425
    • NZOZ Akademicka Poliklinika Stomatologiczna
• Spain
  • Barcelona, Spain, 08022
    • Centro Medico Teknon - Grupo Quironsalud
  • Barcelona, Spain
    • Hospital Odontológico Universitat Barcelona
  • Granada, Spain
    • Facultad de Odontología de la Universidad de Granada
  • Madrid, Spain
    • Instituto Profesor Sada
  • Murcia, Spain, 30003
    • Faculty of Medicine of the UNIVERSITY OF MURCIA
  • Santiago de Compostela, Spain, 15706
    • Hospitalario Universitario de Santiago (CHUS)
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocío

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence and severity of serious and non-serious Adverse Events (AEs).		Up to 24 hours after dose
The test volume formulation acceptability	Patients will answer a question enquiring about the satisfaction with the new oromucosal solution in terms of solution volume	At 6 hours

Collaborators and Investigators

• Sponsor: Unither Pharmaceuticals, France
• Collaborators: AIXIAL Development

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Actual): November 8, 2022
• Study Completion (Actual): November 10, 2022

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: paracetamol
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: UP-CLI-2020-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: At this stage, IPD sharing plan has to been discussed and finalised

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No