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

Unither Pharmaceuticals, France321 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

321

Conditions

Acute Pain

Interventions

nefopam hydrochloride 30mg / paracetamol 500mg X2COMBINATION_PRODUCT

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.

Paracetamol 500 Mg Oral Tablet X2DRUG

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 X2DRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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),

Locations (19)

Hôpital Leuven

Leuven, Belgium

CHU Angers

Angers, France

Outcomes

Primary Outcomes

Ranked Endpoints : 1. Sum of Pain Intensity Differences at 6 Hours (SPID0-6h)

Pain intensity difference (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, T300, T360 min,) after the first Investigational Medicinal Product (IMP) intake and/or right before first intake of rescue medication using a 100-mm Visual Analogic Scale (VAS) compared to baseline. Calculation: Sum of Pain intensity difference (SPID) is the time-weighted summary measure of the total area under the pain intensity difference (PID) curve that integrates serial assessments of pain during x times after the first Investigational Medicinal Product SPID0-6h= SPID0-30min+SPID30min-45min+SPID45min-1h+SPID1h-1h30+SPID1h30-2h+SPID2h-2h30+SPID2h30-3h+SPID3h-4h+SPID4h-5h+SPID5h-6h With: SPIDTime1-Time2 = (PID Theoretical Time1 + PID Theoretical Time2) \* (Theoretical Time2- Theoretical Time1) / 2 SPID min 0-6h = 0 SPID max 0-6h = 36000 The lower score mean a better score

Time frame: 6 hours post-dose

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). Calculation: TOTPAR is the time-weighted summary measure of the total area under the pain release difference curve that integrates serial assessments of pain release during x times after the first Investigational Medicinal Product TOTPAR0-6h=TOTPAR0-30min+TOTPAR30min-45min+TOTPAR45min-1h+TOTPAR1h-1h30+TOTPAR1h30-2h+TOTPAR2h-2h30+TOTPAR2h30-3h+ TOTPAR 3h-4h+ TOTPAR 4h-5h+ TOTPAR 5h-6h With: TOTPARTime1-Time2 = (PAR Time1 + PAR Time2) \* (Time2-Time1) / 2 And with the score of pain relief at T0 = 0 ("none") TOTPAR min 0-6h = 0 TOTPAR max 0-6h = 1800 The higher score mean a better outcome

Time frame: 6 hours post-dose

Proportion of Responder Patients

A responder patient is a subject who achieves a reduction of 50% of pain intensity compared to baseline.

Time frame: 6 hours post-dose

The Patient's Global Impression of Change (PGIC) Questionnaire

Data from ClinicalTrials.gov

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Secondary Outcomes

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 Calculation: TOTPAR is the time-weighted summary measure of the total area under the pain release difference curve that integrates serial assessments of pain release during x times after the first Investigational Medicinal Product TOTPAR0-6h=TOTPAR0-30min+TOTPAR30min-45min+TOTPAR45min-1h+TOTPAR1h-1h30+TOTPAR1h30-2h+TOTPAR2h-2h30+TOTPAR2h30-3h+ TOTPAR 3h-4h+ TOTPAR 4h-5h+ TOTPAR 5h-6h With: TOTPARTime1-Time2 = (PAR Time1 + PAR Time2) \* (Time2-Time1) / 2 And with the score of pain relief at T0 = 0 ("none") TOTPAR min 0-any time = 0 TOTPAR max 0-1h = 300 ; TOTPAR max 0-2h = 600 ;TOTPAR max 0-3h = 900 ;TOTPAR max 0-4h = 1200 ; The higher score mean a better outcome

Time frame: At 1 hour, 2 hours, 3 hours, and 4 hours

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. Calculation: SPID is the time-weighted summary measure of the total area under the pain intensity difference curve that integrates serial assessments of pain during x times after the first IMP SPID0-4h= SPID0-30min+SPID30min-45min+SPID45min-1h+SPID1h-1h30+SPID1h30-2h+SPID2h-2h30+SPID2h30-3h+SPID3h-4h With: SPIDTime1-Time2 = (PID Theoretical Time1 + PID Theoretical Time2) \* (Theoretical Time2- Theoretical Time1) / 2 SPID min 0-any time = 0 SPID max 0-1h = 6000 ; SPID max 0-2h = 12000; SPID max 0-3h = 18000; SPID max 0-4h = 24000 The lower score mean a better score

Time frame: At 1 hour, 2 hours, 3 hours, and 4 hours

The Pain Intensity Differences (PID) Assessment

PID will be calculated using the scores of pain intensity (VAS) at each time point compared to baseline. PID30min = VAS of pain intensity 30min - VAS of pain intensity baseline PID min = 0 / PID max = 100 A higher PID is a better outcome

Time frame: At each timepoint: 30min, At 45min, until at 360 min post-dose

Proportion of Responder Patients.

Time frame: At 1 hour, 2 hours, 3 hours and 4 hours.

Time to the Second Investigational Medicinal Product (IMP) Intake

Time frame: Up to 5 days after first dose

Participant Having Taken a Rescue Analgesic Treatment

Time frame: Up to 10 days after first dose

Sum of Pain Intensity Differences

Pain Intensity Difference (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. Calculation: Sum of Pain Intensity Difference (SPID) is the time-weighted summary measure of the total area under the pain intensity difference curve that integrates serial assessments of pain during x times after the first Investigational Medicinal Product With: SPIDTime1-Time2 = (VAS Theoretical Time1 + VAS Theoretical Time2) \* (Theoretical Time2- Theoretical Time1) / 2 SPID min 0-any time = 0 SPID max 0-day 1 = 144000 ; SPID max 0-day 2 = 288000 ; SPID max 0-day 3 = 432000 ; SPID max 0-day 4 = 576000 ; SPID max 0-day 5 = 720000 ; The lower score means a better outcome

Time frame: At days 1, 2, 3, 4 and 5

Proportion of Patients Having Taken a Rescue Analgesic Treatment Throughout the Study.

Time frame: Up to 10 days after first dose

The Total Dose of Rescue Medication Taken.

Time frame: Up to 10 days after first dose

Mean Duration Under Rescue Medication Over the 5 Days.

Time frame: Up to 5 days after first dose

Number of Investigational Medicinal Product (IMP) Intakes

Time frame: Up to 5 days after first dose

Patient's Global Impression of Change (PGIC) Score

Time frame: Up to 10 days after first dose