Nefopam/Paracetamol Fixed Dose Combination in Acute Pain... | NCT04622735

Name	Class
Excelya	INDUSTRY

Label	Type	Description	Intervention Names
FDC nefopam hydrochloride 30 mg / paracetamol 500 mg (X2)	Experimental	Each dose: 2 tablets (included in masking capsule)	Combination Product: nefopam hydrochloride 30mg / paracetamol 500mg X2
Paracetamol 500 mg (X2)	Active Comparator	Each dose: 2 tablets (included in masking capsule)	Drug: Paracetamol 500 Mg Oral Tablet X2
Nefopam hydrochloride 30 mg (X2)	Active Comparator	Each dose: 2 tablets (included in masking capsule)	Drug: Nefopam HCl 30 MG Oral Tablet X2

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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	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.	6 hours post-dose

Secondary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Occurrence of Adverse Events (Serious and Non-serious Adverse Events).	= Number of Events	Up to 10 days after first dose

Eligibility Module

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),

Name	Affiliation	Role
International Study Coordinator	Birmingham School of Dentistry	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Hôpital Leuven		Leuven			Belgium
CHU Angers

ID	Title	Description
FG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 23, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Posted

Mean

Standard Deviation

score on a scale

6 hours post-dose

ID	Title	Description
OG000	Fixed Dose Combination Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Units	Counts
Participants	OG000107 OG001108 OG002106

Title

Denominators

Categories

Title	Measurements
	OG0008955.4± 8751.8 OG0018458.0± 8831.7 OG0025290.7± 9109.3

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		Mixed Models Analysis		0.0031														Superiority
OG000 OG001		Mixed Models Analysis		0.6787

Primary

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

Posted

Mean

Standard Deviation

score on a scale

6 hours post-dose

ID	Title	Description
OG000	Fixed Dose Combination Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Primary

Proportion of Responder Patients

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

Posted

Count of Participants

Participants

6 hours post-dose

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Primary

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

Posted

Count of Participants

Participants

6 hours post-dose

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Primary

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.

Posted

Count of Participants

Participants

during the first 6 hours

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

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

Posted

Mean

Standard Deviation

score on a scale

At 1 hour, 2 hours, 3 hours, and 4 hours

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

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

Posted

Mean

Standard Deviation

score on a scale

At 1 hour, 2 hours, 3 hours, and 4 hours

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

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

Posted

Mean

Standard Deviation

units on a scale

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

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

Proportion of Responder Patients.

Posted

Count of Participants

Participants

At 1 hour, 2 hours, 3 hours and 4 hours.

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Units

Secondary

Time to the Second Investigational Medicinal Product (IMP) Intake

Posted

Median

95% Confidence Interval

minutes

Up to 5 days after first dose

ID	Title	Description
OG000	Fixed Dose Combination Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

Participant Having Taken a Rescue Analgesic Treatment

Posted

Count of Participants

Participants

Up to 10 days after first dose

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

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

Posted

Mean

Standard Deviation

score on a scale

At days 1, 2, 3, 4 and 5

ID	Title	Description
OG000	Fixed Dose Combination Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

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

Posted

Count of Participants

Participants

Up to 10 days after first dose

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

The Total Dose of Rescue Medication Taken.

Posted

Mean

Standard Deviation

Up to 10 days after first dose

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Units

Secondary

Mean Duration Under Rescue Medication Over the 5 Days.

Posted

Mean

Standard Deviation

hours

Up to 5 days after first dose

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

Number of Investigational Medicinal Product (IMP) Intakes

Posted

Mean

Standard Deviation

intake

Up to 5 days after first dose

ID	Title	Description
OG000	Fixed Dose Combination (FDC) Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Secondary

Patient's Global Impression of Change (PGIC) Score

Posted

Count of Participants

Participants

Up to 10 days after first dose

ID	Title	Description
OG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Other Pre-specified

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

= Number of Events

All population has been analysed

Posted

Number

Adverse Event

Up to 10 days after first dose

ID	Title	Description
OG000	Fixed Dose Combination (FDC) Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
OG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
LYMPHADENOPATHY	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
PALPITATIONS	Cardiac disorders	MedDRA	Systematic Assessment	EG0003 events2 affected107 at risk EG0010 events0 affected108 at risk EG0022 events2 affected106 at risk
TACHYCARDIA	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
EAR PAIN	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0022 events2 affected106 at risk
EAR DISCOMFORT	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
MOTION SICKNESS	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
VISUAL IMPAIRMENT	Eye disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
NAUSEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00014 events13 affected107 at risk EG0018 events8 affected108 at risk EG00213 events13 affected106 at risk
VOMITIN	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 events2 affected107 at risk EG0010 events0 affected108 at risk EG0022 events2 affected106 at risk
DRY MOUTH	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 events3 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
TOOTHACHE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0011 events1 affected108 at risk EG0021 events1 affected106 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
DYSPEPSIA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
MOUTH ULCERATION	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
RETCHING	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
PYREXIA	General disorders	MedDRA	Systematic Assessment	EG0003 events3 affected107 at risk EG0013 events3 affected108 at risk EG0025 events5 affected106 at risk
FATIGUE	General disorders	MedDRA	Systematic Assessment	EG0003 events3 affected107 at risk EG0012 events2 affected108 at risk EG0024 events4 affected106 at risk
SWELLING FACE	General disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0012 events2 affected108 at risk EG0022 events2 affected106 at risk
ASTHENIA	General disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0012 events2 affected108 at risk EG0021 events1 affected106 at risk
CHILLS	General disorders	MedDRA	Systematic Assessment	EG0003 events3 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
FEELING HOT	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
ILLNESS	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
NON-CARDIAC CHEST PAIN	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
ALVEOLAR OSTEITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0003 events2 affected107 at risk EG0013 events3 affected108 at risk EG0024 events4 affected106 at risk
WOUND INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0002 events2 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
ABSCESS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
POST PROCEDURAL INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
RHINITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
RHINITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0022 events1 affected106 at risk
CONTUSION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
POST PROCEDURAL HAEMATOMA	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
POST PROCEDURAL OEDEMA	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
PROCEDURAL PAIN	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
PROCEDURAL VOMITING	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
BODY TEMPERATURE INCREASED	Investigations	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
HEART RATE INCREASED	Investigations	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
MUSCLE TWITCHING	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
MUSCULOSKELETAL CHEST PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
MUSCULOSKELETAL STIFFNESS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
PAIN IN JAW	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
TRISMUS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
HEADACHE	Nervous system disorders	MedDRA	Systematic Assessment	EG0005 events4 affected107 at risk EG0015 events5 affected108 at risk EG0027 events7 affected106 at risk
DIZZINESS	Nervous system disorders	MedDRA	Systematic Assessment	EG0006 events6 affected107 at risk EG0011 events1 affected108 at risk EG0028 events8 affected106 at risk
SOMNOLENCE	Nervous system disorders	MedDRA	Systematic Assessment	EG0007 events7 affected107 at risk EG0014 events4 affected108 at risk EG0022 events2 affected106 at risk
PRESYNCOPE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
DYSGEUSIA	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
HYPOAESTHESIA	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
LETHARGY	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
PARAESTHESIA	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
SYNCOPE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
TREMOR	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
INSOMNIA	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
SLEEP DISORDER	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
CHROMATURIA	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
DYSURIA	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
ERECTILE DYSFUNCTION	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0022 events1 affected106 at risk
HYPERHIDROSIS	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0004 events4 affected107 at risk EG0012 events2 affected108 at risk EG0023 events3 affected106 at risk
NIGHT SWEATS	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0011 events1 affected108 at risk EG0020 events0 affected106 at risk
RASH PRURITIC	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
SKIN DISCOLOURATION	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk
HOT FLUSH	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0021 events1 affected106 at risk
FLUSHING	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected107 at risk EG0010 events0 affected108 at risk EG0020 events0 affected106 at risk

ID	Term
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D011183	Postoperative Complications
D010335	Pathologic Processes

ID	Term
D010079	Oxazocines
D001392	Azocines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines

ID	Title	Description
BG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
BG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
BG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FDC Nefopam Hydrochloride 30 mg / Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.	107	107	39	107
EG001	Paracetamol 500 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.	108	108	25	108
EG002	Nefopam Hydrochloride 30 mg (X2)	Each dose: 2 tablets (included in masking capsule) 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.	106	106	35	106