Clinical trial NCT04622735: Nefopam/Paracetamol Fixed Dose Combination in Acute Pain After Impacted Third Molar Extraction
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Pain
Keywords: Moderate to severe acute pain
Postoperative pain
Third molar extraction
Analgesics
Nefopam
Paracetamol
Multimodal analgesia
Fixed drug combination
Lead sponsor: Unither Pharmaceuticals, France
Sponsor class: INDUSTRY
Collaborators: name: Excelya
First posted: 2020-11-10
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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),

Primary outcomes:
measure: Ranked Endpoints : 1. Sum of Pain Intensity Differences at 6 Hours (SPID0-6h)
timeFrame: 6 hours post-dose
measure: Total Pain Relief at 6 Hours (TOTPAR0-6h)
timeFrame: 6 hours post-dose
measure: Proportion of Responder Patients
timeFrame: 6 hours post-dose
measure: The Patient's Global Impression of Change (PGIC) Questionnaire
timeFrame: 6 hours post-dose
measure: The Onset of Pain Relief
timeFrame: during the first 6 hours
Secondary outcomes:
measure: Total Pain Relief at 1 Hour (TOTPAR0-1h), 2 Hours (TOTPAR0-2h), 3 Hours (TOTPAR0-3h), and 4 Hours (TOTPAR0-4h)
timeFrame: At 1 hour, 2 hours, 3 hours, and 4 hours
measure: Sum of Pain Intensity Differences at 1 Hour (SPID0-1h), 2 Hours (SPID0-2h), 3 Hours (SPID0-3h), and 4 Hours (SPID0-4h)
timeFrame: At 1 hour, 2 hours, 3 hours, and 4 hours
measure: The Pain Intensity Differences (PID) Assessment
timeFrame: At each timepoint: 30min, At 45min, until at 360 min post-dose
measure: Proportion of Responder Patients.
timeFrame: At 1 hour, 2 hours, 3 hours and 4 hours.
measure: Time to the Second Investigational Medicinal Product (IMP) Intake
timeFrame: Up to 5 days after first dose
measure: Participant Having Taken a Rescue Analgesic Treatment
timeFrame: Up to 10 days after first dose
measure: Sum of Pain Intensity Differences
timeFrame: At days 1, 2, 3, 4 and 5
measure: Proportion of Patients Having Taken a Rescue Analgesic Treatment Throughout the Study.
timeFrame: Up to 10 days after first dose
measure: The Total Dose of Rescue Medication Taken.
timeFrame: Up to 10 days after first dose
measure: Mean Duration Under Rescue Medication Over the 5 Days.
timeFrame: Up to 5 days after first dose
measure: Number of Investigational Medicinal Product (IMP) Intakes
timeFrame: Up to 5 days after first dose
measure: Patient's Global Impression of Change (PGIC) Score
timeFrame: Up to 10 days after first dose
Other outcomes:
measure: Occurrence of Adverse Events (Serious and Non-serious Adverse Events).
timeFrame: Up to 10 days after first dose
Locations:
city: Leuven
country: Belgium
facility: Hôpital Leuven
city: Angers
country: France
facility: CHU Angers
city: Marseille
country: France
facility: CHU Marseille
city: Pontoise
country: France
facility: Centre Hospitalier de Pontoise
city: Toulon
country: France
facility: HIA Toulon
city: Tours
country: France
facility: CHU de tours
city: Budapest
country: Hungary
facility: Clinexpert Kft.
city: Budapest
country: Hungary
facility: Óbudai Egészségügyi Centrum
city: Letavertes
country: Hungary
facility: Swan-Med Kft.
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház,
city: Tatabánya
country: Hungary
facility: Szent Borbála Kórház,
city: Zalaegerszeg
country: Hungary
facility: Óbudai Egészségügyi Centrum
city: Moscow
country: Russian Federation
facility: LLC Center for interdisciplinary dentistry & neuro
city: Moscow
country: Russian Federation
facility: State Medico-stomato Univ., by A.I. Evdokimov
city: Yaroslavl
country: Russian Federation
facility: Regional clinical hospital
city: Birmingham
country: United Kingdom
facility: Birmingham School of Dentistry
city: Cardiff
country: United Kingdom
facility: University Dental Hospital
city: Edinburgh
country: United Kingdom
facility: Edinburgh Dental Institute
city: London
country: United Kingdom
facility: BARTS HEALTH NHS TRUST Royal London Hospital
Study officials:
affiliation: Birmingham School of Dentistry
name: International Study Coordinator
role: PRINCIPAL_INVESTIGATOR
References: