Nefopam/Paracetamol Fixed Dose Combination in Acute Pain After Impacted Third Molar Extraction

Acute Pain Clinical Trial

Official title:

A Comparative, Randomized, Double-blind, 3-arm Parallel, Phase III Study to Evaluate the Efficacy and Safety of a Fixed Dose Combination of Nefopam/Paracetamol Taken Orally in Moderate to Severe Pain After Impacted Third Molar Extraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04622735
• Other study ID #: UP-CLI-2019-002
• Status: Completed
• Phase: Phase 3
• Start date: February 22, 2020
• Est. completion date: October 20, 2022

Study information

• Verified date: November 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 and multiple doses of a new fixed dose combination of nefopam hydrochloride 30 mg and paracetamol 500mg taken orally in comparison to each single component.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 321
• Est. completion date: October 20, 2022
• Est. primary completion date: October 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Main Inclusion Criteria:

• Male and female patient aged from 18 years up to 65 years,
• Patient scheduled to undergo the surgical removal of at least one fully or partially impacted third mandibular molar requiring bone removal under short-acting local anaesthetic (mepivacaine or lidocaine) with or without vasoconstrictor,
• Patient weighing > 50 kg,
• Patient who has signed a written informed consent prior to any study-related procedures.

Additional inclusion criteria after surgery (randomization):

1. Patient experiencing moderate to severe pain within 4 hours after the dental extraction, defined by a baseline pain intensity Visual Analogic Scale (VAS) score = 50 mm,

2. Third molar extraction(s) 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)

Main Exclusion Criteria:

• Patient treated by analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) within 3 days preceding the day of randomization or within 5 times the elimination half-life whichever the longest,
• Woman with positive results on a urine pregnancy test or breastfeeding woman or woman of childbearing potential without an effective contraception,
• Patient with a history of convulsive disorders,
• Patient taking mono-amine-oxidase (MAO) inhibitors (including but not limited to selegiline, isocarboxazid, tranylcypromine, phenelzine…),
• Patient with an abnormal cardiac condition: medically significant disorders of cardiac rate and/or rhythm,
• Patient with known anaemia,
• Patient with known pulmonary disease,
• Patient with known active gastric or duodenal ulcer or a history of recurrent gastrointestinal ulcer/bleeding,
• Patient with known glaucoma,
• Patients with a prostatic hyperplasia or urinary retention,
• Patient with current or chronic history of liver disease, or known hepatic or biliary abnormalities,
• Patient with a current or chronic history of severe renal impairment (glomerular filtration below 30 mL/min),

Related Conditions & MeSH terms

• Acute Pain

Intervention

Combination Product:
• nefopam hydrochloride 30mg / paracetamol 500mg X2
The first intake is taken right after randomization. Then on-demand period (5 days maximum) respecting a 6-hour interval between intakes, and up to 3 intakes per day.

Drug:
• Paracetamol 500 Mg Oral Tablet X2
The first intake is taken right after randomization. Then on-demand period (5 days maximum) respecting a 6-hour interval between intakes, and up to 3 intakes per day.
• Nefopam HCl 30 MG Oral Tablet X2
The first intake is taken right after randomization. Then on-demand period (5 days maximum) respecting a 6-hour interval between intakes, and up to 3 intakes per day.

Locations

Country	Name	City	State
Belgium	Hôpital Leuven	Leuven
France	CHU Angers	Angers
France	CHU Marseille	Marseille
France	Centre Hospitalier de Pontoise	Pontoise
France	HIA Toulon	Toulon
France	CHU de tours	Tours
Hungary	Clinexpert Kft.	Budapest
Hungary	Óbudai Egészségügyi Centrum	Budapest
Hungary	Swan-Med Kft.	Letavertes
Hungary	Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház,	Nyíregyháza
Hungary	Szent Borbála Kórház,	Tatabánya
Hungary	Óbudai Egészségügyi Centrum	Zalaegerszeg
Russian Federation	LLC Center for interdisciplinary dentistry & neuro	Moscow
Russian Federation	State Medico-stomato Univ., by A.I. Evdokimov	Moscow
Russian Federation	Regional clinical hospital	Yaroslavl
United Kingdom	Birmingham School of Dentistry	Birmingham
United Kingdom	University Dental Hospital	Cardiff
United Kingdom	Edinburgh Dental Institute	Edinburgh
United Kingdom	BARTS HEALTH NHS TRUST Royal London Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Unither Pharmaceuticals, France	EXCELYA Bordeaux

Countries where clinical trial is conducted

Belgium,  France,  Hungary,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Occurrence and severity of adverse events (serious and non-serious adverse events).		Up to 10 days after first dose
Primary	Ranked endpoints : 1. Sum of Pain Intensity Differences at 6 hours (SPID0-6h)	Pain intensity difference will be calculated using the score of pain intensity assessed by the patient at defined time points (T30, T45, T60, T90, T120, T150, T180, T240, T300, T360 min,) after the first IMP intake and/or right before first intake of rescue medication using a 100-mm Visual Analogic Scale (VAS) compared to baseline.	6 hours post-dose
Primary	Total Pain Relief at 6 hours (TOTPAR0-6h)	Pain Relief will be assessed by the patient at defined time points (T30, T45, T60, T90, T120, T150, T180, T240, T300, T360 min) after the first IMP intake and/or right before first intake of rescue medication using a 5-point verbal rating scale (VRS).	6 hours post-dose
Primary	Proportion of responder patients	A responder patient is a subject who achieves a reduction of 50% of pain intensity compared to baseline.	6 hours post-dose
Primary	The Patient's Global Impression of Change (PGIC) questionnaire		6 hours post-dose
Primary	The onset of pain relief	Score of pain intensity will be assessed by the patient at defined time points (T30, T45, T60, T90, T120, T150, T180, T240, T300, T360 min). The time point of the first assessment obtaining a score = 30 mm will be retained as time score of onset of pain relief.	during the first 6 hours
Secondary	Total Pain Relief at 1 hour (TOTPAR0-1h), 2 hours (TOTPAR0-2h), 3 hours (TOTPAR0-3h), and 4 hours (TOTPAR0-4h)	Pain relief (PAR) will be assessed by the patient at defined time points (T30, T45, T60, T90, T120, T150, T180, T240 min) after the first IMP intake and/or right before first intake of rescue medication using a 5-point verbal rating scale	At 1 hour, 2 hours, 3 hours, and 4 hours
Secondary	Sum of Pain Intensity Differences at 1 hour (SPID0-1h), 2 hours (SPID0-2h), 3 hours (SPID0-3h), and 4 hours (SPID0-4h)	PID will be calculated using the score of pain intensity assessed by the patient at defined time points (T30, T45, T60, T90, T120, T150, T180, T240 min) after the first IMP intake and/or right before first intake of rescue medication using a 100-mm VAS compared to baseline.	At 1 hour, 2 hours, 3 hours, and 4 hours
Secondary	The Pain Intensity Differences (PID) assessment	PID will be calculated using the scores of pain intensity (VAS) at each time point compared to baseline.	At each timepoint: 30min, At 45min, until at 360 min post-dose
Secondary	Proportion of responder patients.		At 1 hour, 2 hours, 3 hours and 4 hours.
Secondary	Time to the second IMP intake		Up to 5 days after first dose
Secondary	Time to rescue medication intake		Up to 10 days after first dose
Secondary	Sum of Pain Intensity Differences (SPID)	PID will be calculated using the score of pain intensity assessed by the patient at defined time points using a 100-mm visual Analog Scale (VAS) compared to baseline.	At days 1, 2, 3, 4 and 5
Secondary	Proportion of patients having taken a rescue analgesic treatment throughout the study.		Up to 10 days after first dose
Secondary	The total dose of rescue medication taken.		Up to 10 days after first dose
Secondary	Mean duration under rescue medication over the 5 days.		Up to 5 days after first dose
Secondary	Number of IMP intakes		Up to 5 days after first dose
Secondary	Patient's Global Impression of Change (PGIC) score		Up to 10 days after first dose