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Completed

NCT Number: NCT04622735

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

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.

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Key information

Conditions

Acute Pain Neurologic Manifestations Pain Pain, Postoperative Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hôpital Leuven, Leuven, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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):

  • 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,
  • 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),

Treatment and study plan

nefopam hydrochloride 30mg / paracetamol 500mg X2

Combination 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 X2

Drug

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.

Other names: Acetaminophen

Nefopam HCl 30 MG Oral Tablet X2

Drug

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.

Primary outcomes

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

    Time frame: 6 hours post-dose

    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

  2. Total Pain Relief at 6 Hours (TOTPAR0-6h)

    Time frame: 6 hours post-dose

    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

  3. Proportion of Responder Patients

    Time frame: 6 hours post-dose

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

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

    Time frame: 6 hours post-dose

  5. The Onset of Pain Relief

    Time frame: during the first 6 hours

    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.

Secondary outcomes

  1. Total Pain Relief at 1 Hour (TOTPAR0-1h), 2 Hours (TOTPAR0-2h), 3 Hours (TOTPAR0-3h), and 4 Hours (TOTPAR0-4h)

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

    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

  2. Sum of Pain Intensity Differences at 1 Hour (SPID0-1h), 2 Hours (SPID0-2h), 3 Hours (SPID0-3h), and 4 Hours (SPID0-4h)

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

    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

  3. The Pain Intensity Differences (PID) Assessment

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

    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

  4. Proportion of Responder Patients.

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

  5. Time to the Second Investigational Medicinal Product (IMP) Intake

    Time frame: Up to 5 days after first dose

  6. Participant Having Taken a Rescue Analgesic Treatment

    Time frame: Up to 10 days after first dose

  7. Sum of Pain Intensity Differences

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

    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

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

    Time frame: Up to 10 days after first dose

  9. The Total Dose of Rescue Medication Taken.

    Time frame: Up to 10 days after first dose

  10. Mean Duration Under Rescue Medication Over the 5 Days.

    Time frame: Up to 5 days after first dose

  11. Number of Investigational Medicinal Product (IMP) Intakes

    Time frame: Up to 5 days after first dose

  12. Patient's Global Impression of Change (PGIC) Score

    Time frame: Up to 10 days after first dose

Other outcomes

  1. Occurrence of Adverse Events (Serious and Non-serious Adverse Events).

    Time frame: Up to 10 days after first dose

    = Number of Events

Sponsors and collaborators

Lead sponsor

Unither Pharmaceuticals, France

Industry

Collaborators

  • Excelya

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Nov 10, 2020
Registry last updated
Nov 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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