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

Acute Pain Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04640376
• Other study ID #: UP-CLI-2020-001
• Status: Completed
• Phase: Phase 3
• Start date: March 24, 2021
• Est. completion date: November 10, 2022

Study information

• Verified date: October 2022
• Source: Unither Pharmaceuticals, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 407
• Est. completion date: November 10, 2022
• Est. primary completion date: November 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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);

Related Conditions & MeSH terms

• Acute Pain

Intervention

Drug:
• Paracetamol Uniflash 125mg
Oromucosal solution 1.25 mL for buccal use
• Panadol 500 MG Oral Tablet X1
Tablet masked in capsule
• Panadol 500 MG Oral Tablet X2
Tablet masked in capsule
• Placebo
Dummy treatment

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux
France	CHRU de Clermont Ferrand	Clermont Ferrand
France	Hôpital Louis Mourier	Colombes
France	CHU Montpellier	Montpellier
France	CHU de Strasbourg	Strasbourg
Italy	Università degli Studi di Milano	Milano
Italy	Department of maxilla facial Surgery -University of Udine	Udine
Poland	University Central Stomatology GDANSK	Gdansk
Poland	Dental Practice	Lodz
Poland	Oral Surgery Department, Central Clinical Hospital	Lodz
Poland	Oral surgery Medical University of Lublin	Lublin
Poland	AW Clinic	Warszawa
Poland	NZOZ Akademicka Poliklinika Stomatologiczna	Wroclaw
Spain	Centro Médico Teknon - Grupo Quironsalud	Barcelona
Spain	Hospital Odontológico Universitat Barcelona	Barcelona
Spain	Facultad de Odontología de la Universidad de Granada	Granada
Spain	Instituto Profesor Sada	Madrid
Spain	Faculty of Medicine of the UNIVERSITY OF MURCIA	Murcia
Spain	Hospitalario Universitario de Santiago (CHUS)	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocio	Sevilla

Sponsors (2)

Lead Sponsor	Collaborator
Unither Pharmaceuticals, France	AIXIAL Development

Countries where clinical trial is conducted

France,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Occurrence and severity of serious and non-serious Adverse Events (AEs).		Up to 24 hours after dose
Other	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
Primary	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
Primary	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
Primary	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
Primary	Patient Global Impression of Change (PGIC) versus 1000 mg of the reference oral paracetamol (Panadol®)		At 60 minutes
Primary	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	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	Period of time before taking rescue analgesic treatment intake.		Up to 24 hours after dose
Secondary	Proportion of patients taking a rescue analgesic treatment.		At 6 hours
Secondary	Patient Global Impression of Change (PGIC) versus 500 mg of the reference oral paracetamol (Panadol®)		At 60 minutes
Secondary	Patient Global Impression of Change (PGIC) versus 500 mg and 1000 mg of the reference oral paracetamol (Panadol®)		At 360 minutes