Back to resultsNefopam/Paracetamol Fixed Dose Combination in Acute Pain After Impacted Third Molar Extraction
Primary Purpose
Acute Pain
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
nefopam hydrochloride 30mg / paracetamol 500mg X2
Paracetamol 500 Mg Oral Tablet X2
Nefopam HCl 30 MG Oral Tablet X2
Sponsored by
About this trial
This is an interventional treatment trial for Acute Pain focused on measuring Moderate to severe acute pain, Postoperative pain, Third molar extraction, Analgesics, Nefopam, Paracetamol, Multimodal analgesia, Fixed drug combination
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):
- 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),
Sites / Locations
- Hôpital Leuven
- CHU Angers
- CHU Marseille
- Centre Hospitalier de Pontoise
- HIA Toulon
- CHU de tours
- Clinexpert Kft.
- Óbudai Egészségügyi Centrum
- Swan-Med Kft.
- Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház,
- Szent Borbála Kórház,
- Óbudai Egészségügyi Centrum
- LLC Center for interdisciplinary dentistry & neuro
- State Medico-stomato Univ., by A.I. Evdokimov
- Regional clinical hospital
- Birmingham School of Dentistry
- University Dental Hospital
- Edinburgh Dental Institute
- BARTS HEALTH NHS TRUST Royal London Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
FDC nefopam hydrochloride 30 mg / paracetamol 500 mg (X2)
Paracetamol 500 mg (X2)
Nefopam hydrochloride 30 mg (X2)
Arm Description
Each dose: 2 tablets (included in masking capsule)
Each dose: 2 tablets (included in masking capsule)
Each dose: 2 tablets (included in masking capsule)
Outcomes
Primary Outcome Measures
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.
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).
Proportion of responder patients
A responder patient is a subject who achieves a reduction of 50% of pain intensity compared to baseline.
The Patient's Global Impression of Change (PGIC) questionnaire
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.
Secondary Outcome Measures
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
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.
The Pain Intensity Differences (PID) assessment
PID will be calculated using the scores of pain intensity (VAS) at each time point compared to baseline.
Proportion of responder patients.
Time to the second IMP intake
Time to rescue medication intake
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.
Proportion of patients having taken a rescue analgesic treatment throughout the study.
The total dose of rescue medication taken.
Mean duration under rescue medication over the 5 days.
Number of IMP intakes
Patient's Global Impression of Change (PGIC) score
Full Information
NCT ID
NCT04622735
First Posted
October 22, 2020
Last Updated
November 10, 2022
Sponsor
Unither Pharmaceuticals, France
Collaborators
EXCELYA Bordeaux
1. Study Identification
Unique Protocol Identification Number
NCT04622735
Brief Title
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
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
February 22, 2020 (Actual)
Primary Completion Date
October 12, 2022 (Actual)
Study Completion Date
October 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Unither Pharmaceuticals, France
Collaborators
EXCELYA Bordeaux
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Pain
Keywords
Moderate to severe acute pain, Postoperative pain, Third molar extraction, Analgesics, Nefopam, Paracetamol, Multimodal analgesia, Fixed drug combination
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
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.
Allocation
Randomized
Enrollment
321 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FDC nefopam hydrochloride 30 mg / paracetamol 500 mg (X2)
Arm Type
Experimental
Arm Description
Each dose: 2 tablets (included in masking capsule)
Arm Title
Paracetamol 500 mg (X2)
Arm Type
Active Comparator
Arm Description
Each dose: 2 tablets (included in masking capsule)
Arm Title
Nefopam hydrochloride 30 mg (X2)
Arm Type
Active Comparator
Arm Description
Each dose: 2 tablets (included in masking capsule)
Intervention Type
Combination Product
Intervention Name(s)
nefopam hydrochloride 30mg / paracetamol 500mg X2
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Paracetamol 500 Mg Oral Tablet X2
Other Intervention Name(s)
Acetaminophen
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Nefopam HCl 30 MG Oral Tablet X2
Intervention Description
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 Outcome Measure Information:
Title
Ranked endpoints : 1. Sum of Pain Intensity Differences at 6 hours (SPID0-6h)
Description
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.
Time Frame
6 hours post-dose
Title
Total Pain Relief at 6 hours (TOTPAR0-6h)
Description
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).
Time Frame
6 hours post-dose
Title
Proportion of responder patients
Description
A responder patient is a subject who achieves a reduction of 50% of pain intensity compared to baseline.
Time Frame
6 hours post-dose
Title
The Patient's Global Impression of Change (PGIC) questionnaire
Time Frame
6 hours post-dose
Title
The onset of pain relief
Description
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.
Time Frame
during the first 6 hours
Secondary Outcome Measure Information:
Title
Total Pain Relief at 1 hour (TOTPAR0-1h), 2 hours (TOTPAR0-2h), 3 hours (TOTPAR0-3h), and 4 hours (TOTPAR0-4h)
Description
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
Time Frame
At 1 hour, 2 hours, 3 hours, and 4 hours
Title
Sum of Pain Intensity Differences at 1 hour (SPID0-1h), 2 hours (SPID0-2h), 3 hours (SPID0-3h), and 4 hours (SPID0-4h)
Description
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.
Time Frame
At 1 hour, 2 hours, 3 hours, and 4 hours
Title
The Pain Intensity Differences (PID) assessment
Description
PID will be calculated using the scores of pain intensity (VAS) at each time point compared to baseline.
Time Frame
At each timepoint: 30min, At 45min, until at 360 min post-dose
Title
Proportion of responder patients.
Time Frame
At 1 hour, 2 hours, 3 hours and 4 hours.
Title
Time to the second IMP intake
Time Frame
Up to 5 days after first dose
Title
Time to rescue medication intake
Time Frame
Up to 10 days after first dose
Title
Sum of Pain Intensity Differences (SPID)
Description
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.
Time Frame
At days 1, 2, 3, 4 and 5
Title
Proportion of patients having taken a rescue analgesic treatment throughout the study.
Time Frame
Up to 10 days after first dose
Title
The total dose of rescue medication taken.
Time Frame
Up to 10 days after first dose
Title
Mean duration under rescue medication over the 5 days.
Time Frame
Up to 5 days after first dose
Title
Number of IMP intakes
Time Frame
Up to 5 days after first dose
Title
Patient's Global Impression of Change (PGIC) score
Time Frame
Up to 10 days after first dose
Other Pre-specified Outcome Measures:
Title
Occurrence and severity of adverse events (serious and non-serious adverse events).
Time Frame
Up to 10 days after first dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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):
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),
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
International Study Coordinator
Organizational Affiliation
Birmingham School of Dentistry
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Leuven
City
Leuven
Country
Belgium
Facility Name
CHU Angers
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
CHU Marseille
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Centre Hospitalier de Pontoise
City
Pontoise
ZIP/Postal Code
95300
Country
France
Facility Name
HIA Toulon
City
Toulon
ZIP/Postal Code
83800
Country
France
Facility Name
CHU de tours
City
Tours
ZIP/Postal Code
37170
Country
France
Facility Name
Clinexpert Kft.
City
Budapest
Country
Hungary
Facility Name
Óbudai Egészségügyi Centrum
City
Budapest
Country
Hungary
Facility Name
Swan-Med Kft.
City
Letavertes
Country
Hungary
Facility Name
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház,
City
Nyíregyháza
Country
Hungary
Facility Name
Szent Borbála Kórház,
City
Tatabánya
Country
Hungary
Facility Name
Óbudai Egészségügyi Centrum
City
Zalaegerszeg
Country
Hungary
Facility Name
LLC Center for interdisciplinary dentistry & neuro
City
Moscow
ZIP/Postal Code
141207
Country
Russian Federation
Facility Name
State Medico-stomato Univ., by A.I. Evdokimov
City
Moscow
Country
Russian Federation
Facility Name
Regional clinical hospital
City
Yaroslavl
ZIP/Postal Code
150062
Country
Russian Federation
Facility Name
Birmingham School of Dentistry
City
Birmingham
ZIP/Postal Code
B5 7EG
Country
United Kingdom
Facility Name
University Dental Hospital
City
Cardiff
ZIP/Postal Code
CF14 4XY
Country
United Kingdom
Facility Name
Edinburgh Dental Institute
City
Edinburgh
ZIP/Postal Code
EH3 9HX
Country
United Kingdom
Facility Name
BARTS HEALTH NHS TRUST Royal London Hospital
City
London
ZIP/Postal Code
E1 1FR
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Nefopam/Paracetamol Fixed Dose Combination in Acute Pain After Impacted Third Molar Extraction
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