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

Sponsor
Unither Pharmaceuticals, France (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04622735
Collaborator
EXCELYA Bordeaux (Other)
321
Enrollment
24
Locations
3
Arms
31.3
Anticipated Duration (Months)
13.4
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Combination Product: nefopam hydrochloride 30mg / paracetamol 500mg X2
  • Drug: Paracetamol 500 Mg Oral Tablet X2
  • Drug: Nefopam HCl 30 MG Oral Tablet X2
 Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
321 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
Double-blind. Participants, investigators, and all persons involved in the conduct, data management, and analysis of the study will be fully blinded to the participant's treatment.
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 22, 2020
Anticipated Primary Completion Date :
Oct 1, 2022
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: FDC nefopam hydrochloride 30 mg / paracetamol 500 mg (X2)

Each dose: 2 tablets (included in masking capsule)

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.
Active Comparator: Paracetamol 500 mg (X2)

Each dose: 2 tablets (included in masking capsule)

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.
Other Names:
  • Acetaminophen

    		•
    Active Comparator: Nefopam hydrochloride 30 mg (X2)

    Each dose: 2 tablets (included in masking capsule)

    Drug: 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.

    Outcome Measures

    Primary Outcome Measures

    1. Ranked endpoints : 1. Sum of Pain Intensity Differences at 6 hours (SPID0-6h) [6 hours post-dose]

      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.

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

    3. Proportion of responder patients [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 [6 hours post-dose]

    5. The onset of pain relief [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 Outcome Measures

    1. Total Pain Relief at 1 hour (TOTPAR0-1h), 2 hours (TOTPAR0-2h), 3 hours (TOTPAR0-3h), and 4 hours (TOTPAR0-4h) [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

    2. Sum of Pain Intensity Differences at 1 hour (SPID0-1h), 2 hours (SPID0-2h), 3 hours (SPID0-3h), and 4 hours (SPID0-4h) [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.

    3. The Pain Intensity Differences (PID) assessment [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.

    4. Proportion of responder patients. [At 1 hour, 2 hours, 3 hours and 4 hours.]

    5. Time to the second IMP intake [Up to 5 days after first dose]

    6. Time to rescue medication intake [Up to 10 days after first dose]

    7. Sum of Pain Intensity Differences (SPID) [At days 1, 2, 3, 4 and 5]

      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.

    8. Proportion of patients having taken a rescue analgesic treatment throughout the study. [Up to 10 days after first dose]

    9. The total dose of rescue medication taken. [Up to 10 days after first dose]

    10. Mean duration under rescue medication over the 5 days. [Up to 5 days after first dose]

    11. Number of IMP intakes [Up to 5 days after first dose]

    12. Patient's Global Impression of Change (PGIC) score [Up to 10 days after first dose]

    Other Outcome Measures

    1. Occurrence and severity of adverse events (serious and non-serious adverse events). [Up to 10 days after first dose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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),

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hôpital Erasme- ULB- Bruxelles Bruxelles Belgium
    2 Hôpital Leuven Leuven Belgium
    3 CH Amiens Amiens France 80054
    4 CHU Angers Angers France 49933
    5 Ch Boulogne Boulogne France
    6 CHU Marseille Marseille France 13385
    7 Centre Hospitalier de Pontoise Pontoise France 95300
    8 HIA Toulon Toulon France 83800
    9 CHU de tours Tours France 37170
    10 Clinexpert Kft. Budapest Hungary
    11 Óbudai Egészségügyi Centrum Budapest Hungary
    12 Swan-Med Kft. Letavertes Hungary
    13 Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház, Nyíregyháza Hungary
    14 SmileDent Kft. Szeged Hungary
    15 Szent Borbála Kórház, Tatabánya Hungary
    16 Óbudai Egészségügyi Centrum Zalaegerszeg Hungary
    17 LLC Center for interdisciplinary dentistry & neuro Moscow Russian Federation 141207
    18 Clinic of Moscow State Medical University Moscow Russian Federation
    19 State Medico-stomato Univ., by A.I. Evdokimov Moscow Russian Federation
    20 Regional clinical hospital Yaroslavl Russian Federation 150062
    21 Birmingham School of Dentistry Birmingham United Kingdom B5 7EG
    22 University Dental Hospital Cardiff United Kingdom CF14 4XY
    23 Edinburgh Dental Institute Edinburgh United Kingdom EH3 9HX
    24 BARTS HEALTH NHS TRUST Royal London Hospital London United Kingdom E1 1FR

    Sponsors and Collaborators

    • Unither Pharmaceuticals, France
    • EXCELYA Bordeaux

    Investigators

    • Principal Investigator: International Study Coordinator, Birmingham School of Dentistry

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Unither Pharmaceuticals, France
    ClinicalTrials.gov Identifier:
    NCT04622735
    Other Study ID Numbers:
    • UP-CLI-2019-002
    First Posted:
    Nov 10, 2020
    Last Update Posted:
    Jun 1, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Unither Pharmaceuticals, France
    Moderate to severe acute pain
    Postoperative pain
    Third molar extraction
    Analgesics
    Nefopam
    Paracetamol
    Multimodal analgesia
    Fixed drug combination
    Additional relevant MeSH terms:
    Acute Pain
    Acetaminophen
    Nefopam

    Study Results

    No Results Posted as of Jun 1, 2022