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

NCT04640376 | Completed Phase 3

• 1 other identifier: UP-CLI-2020-001
• Study Type: interventional
• Target: 407
• Locations: 4 countries
• Sites: 20

Brief 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.

Conditions

Acute Pain

Keywords

paracetamol

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (8)

• 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).

  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®)).

  At 60 minutes

• Proportion of responders at 5 minutes, 10 minutes, 30 minutes, 45 minutes, 2 hours, 4 hours and then 6 hours.

  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)

  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

Other Outcomes (2)

• Occurrence and severity of serious and non-serious Adverse Events (AEs).

  Up to 24 hours after dose

• The test volume formulation acceptability

  At 6 hours

Study Arms (4)

Paracetamol UNIFLASH 125mg

EXPERIMENTAL

1 sachet Paracetamol UNIFLASH 125mg + 2 placebo capsule

Drug: Paracetamol Uniflash 125mg; Drug: Placebo

Placebo

PLACEBO COMPARATOR

1 Placebo sachet + 2 placebo capsule

Drug: Placebo

Paracetamol 500mg

ACTIVE COMPARATOR

1 Placebo sachet + 1 placebo capsule + 1 capsule Panadol 500mg

Drug: Panadol 500 MG Oral Tablet X1; Drug: Placebo

Paracetamol 1000mg

ACTIVE COMPARATOR

1 Placebo sachet + 2 capsules Panadol 500mg

Drug: Panadol 500 MG Oral Tablet X2; Drug: Placebo

Interventions

Paracetamol Uniflash 125mg DRUG

Oromucosal solution 1.25 mL for buccal use

Paracetamol UNIFLASH 125mg

Panadol 500 MG Oral Tablet X1 DRUG

Tablet masked in capsule

Paracetamol 500mg

Panadol 500 MG Oral Tablet X2 DRUG

Tablet masked in capsule

Paracetamol 1000mg

Placebo DRUG

Dummy treatment

Paracetamol 1000mg; Paracetamol 500mg; Paracetamol UNIFLASH 125mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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).

You may not qualify if:

• 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);

Sponsors & Collaborators

• Unither Pharmaceuticals, France: lead
• AIXIAL Development: collaborator

Study Sites (20)

CHU de Bordeaux

Bordeaux, 33075, France

Location

CHRU de Clermont Ferrand

Clermont-Ferrand, 63003, France

Location

Hôpital Louis Mourier

Colombes, 92700, France

Location

CHU Montpellier

Montpellier, 34070, France

Location

CHU de Strasbourg

Strasbourg, France

Location

Università degli Studi di Milano

Milan, Italy

Location

Department of maxilla facial Surgery -University of Udine

Udine, Italy

Location

University Central Stomatology GDANSK

Gdansk, Poland

Location

Oral Surgery Department, Central Clinical Hospital

Lodz, 92213, Poland

Location

Dental Practice

Lodz, Poland

Location

Oral surgery Medical University of Lublin

Lublin, Poland

Location

AW Clinic

Warsaw, Poland

Location

NZOZ Akademicka Poliklinika Stomatologiczna

Wroclaw, 50425, Poland

Location

Centro Médico Teknon - Grupo Quironsalud

Barcelona, 08022, Spain

Location

Hospital Odontológico Universitat Barcelona

Barcelona, Spain

Location

Facultad de Odontología de la Universidad de Granada

Granada, Spain

Location

Instituto Profesor Sada

Madrid, Spain

Location

Faculty of Medicine of the UNIVERSITY OF MURCIA

Murcia, 30003, Spain

Location

Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

MeSH Terms

Conditions

Acute Pain

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind. Participants, Investigators, and all persons involved in the conduct, data management, and analysis of the study will be fully blind to the participant's treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: November 23, 2020
• Study Start: March 24, 2021
• Primary Completion: November 8, 2022
• Study Completion: November 10, 2022
• Last Updated: November 14, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); IT (2); PL (6); ES (7)