Clinical trial • Phase II • Musculoskeletal

NEFOPAM HYDROCHLORIDE for Postoperative pain after total knee arthroplasty

Phase II trial of NEFOPAM HYDROCHLORIDE for Postoperative pain after total knee arthroplasty.

Overview

Trial Therapeutic Area
Musculoskeletal
Trial Disease
Postoperative pain after total knee arthroplasty
Trial Stage
Phase II
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
31-05-2024
First CTIS Authorization Date
30-07-2024

Trial design

Randomised, placebo: schweppes™ (placebo). test product: nefopam panpharma 20 mg/2 ml (product name indicates strength 20 mg/2 ml; productchangedescription: oral administratition). auxiliary/rescue analgesics: various marketed morphine products (morphine chlorhydrate/ sulfate; formulations listed) used as auxiliary treatment. doses and schedules not specified in the available data.-controlled Phase II trial across 1 site in France.

Randomised
Yes
Comparator
Placebo: Schweppes™ (placebo). Test product: NEFOPAM PANPHARMA 20 mg/2 mL (product name indicates strength 20 mg/2 mL; productChangeDescription: Oral administratition). Auxiliary/rescue analgesics: various marketed morphine products (MORPHINE CHLORHYDRATE/ SULFATE; formulations listed) used as auxiliary treatment. Doses and schedules not specified in the available data.
Target Sample Size
50

Eligibility

Recruits 50 No vulnerable population selected. Only adults (Patient over 18). Consent is provided by the patient: "Patient having agreed to take part in the study and having signed the informed consent form." Subject information and informed consent form document is listed (L1_ SIS and IC). No assent provisions described..

Pregnancy Exclusion
Pregnancy or breastfeeding
Vulnerable Population
No vulnerable population selected. Only adults (Patient over 18). Consent is provided by the patient: "Patient having agreed to take part in the study and having signed the informed consent form." Subject information and informed consent form document is listed (L1_ SIS and IC). No assent provisions described.

Inclusion criteria

  • {"criterion_text":"- Patient over 18.\n- Patient scheduled for primary PTG under spinal anesthesia, in the orthopedics department of the Croix-Rousse hospital.\n- Patient with an American Society of Anesthesiology (ASA) score between I and III.\n- Patient having agreed to take part in the study and having signed the informed consent form.\n- Patient entitled to social security benefits.\n- Patient willing to return for all study visits."}

Exclusion criteria

  • {"criterion_text":"- Any contraindication for nefopam (known hypersensitivity, past medical history of seizures, urinary retention, benign prostate hyperplasia, angle glaucoma, ischemic cardiomyopathy waiting for revascularization, atrial fibrillation)\n- Medical conditions known to influence the pharmacokinetics of nefopam (chronic kidney failure with Glomerular Filtration Rate (GFR) <30mL/min/1,73m2, liver failure, current treatment with rifampicin, carbamazepine, azoles fungicides, macrolides)\n- Current treatment with benzodiazepines, anxiolytics, antidepressants, histamine H1 antagonists, neuroleptics, baclofen, thalidomide, barbiturates\n- Medical history of gastric or esophageal surgery.\n- Phenylketonuria\n- Pregnancy or breastfeeding\n- Past use of oral nefopam"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Total morphine consumption within 24h after the surgery.","definition_or_measurement_approach":"Total morphine consumption measured within 24 hours after surgery (primary objective: measure whether orally administered nefopam reduces morphine consumption at 24h after total knee replacement)."}

Secondary endpoints

  • {"endpoint_text":"- Pressure Pain Threshold","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Punctate Pain Intensity","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Allodynia zone","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Pain intensity","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Self reported safety outcomes","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Measures of safety outcomes","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Plasmatic and cerebrospinal fluid concentration of nefopam","definition_or_measurement_approach":"Plasma and CSF concentrations measured (secondary objectives specify measurement 2 hours after oral administration)."}
  • {"endpoint_text":"- Plasmatic and cerebrospinal fluid concentration of nefopam-beta-D-glucuronide","definition_or_measurement_approach":"Plasma and CSF concentrations measured (secondary objectives specify measurement 2 hours after oral administration)."}
  • {"endpoint_text":"- Plasmatic and cerebrospinal fluid concentration of nefopam-N-oxyde","definition_or_measurement_approach":"Plasma and CSF concentrations measured (secondary objectives specify measurement 2 hours after oral administration)."}
  • {"endpoint_text":"- Plasmatic and cerebrospinal fluid concentration of nefopam-N-demethyl","definition_or_measurement_approach":"Plasma and CSF concentrations measured (secondary objectives specify measurement 2 hours after oral administration)."}
  • {"endpoint_text":"- Plasmatic and cerebrospinal fluid concentration of Nefopam hydrochloride","definition_or_measurement_approach":"Plasma and CSF concentrations measured (secondary objectives specify measurement 2 hours after oral administration)."}
  • {"endpoint_text":"- Persistent postoperative pain - DN4 (or DN2 by phone)","definition_or_measurement_approach":"Persistent postoperative pain assessed using DN4 questionnaire (or DN2 by phone)."}
  • {"endpoint_text":"- Persistent postoperative pain - DN4","definition_or_measurement_approach":"Persistent postoperative pain assessed using DN4 questionnaire."}

Recruitment

Planned Sample Size
50
Recruitment Window Months
24
Consent Approach
Informed consent obtained from the patient (adult) who must agree and sign the informed consent form. Subject information and informed consent form document (L1_ SIS and IC) is listed. Study materials include French translations; consent appears to be in French. No assent process described.

Geography

Total Number Of Sites
1
Total Number Of Participants
50

France

Earliest CTIS Part Ii Submission Date
14-06-2024
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
682
Number Of Sites
1
Number Of Participants
50

Sites

Site Name
Hospital La Croix Rousse Hcl
Department Name
Anesthésie Réanimation
Principal Investigator Name
Frédéric Aubrun
Principal Investigator Email
frederic.aubrun@chu-lyon.fr
Contact Person Name
Frédéric Aubrun
Contact Person Email
frederic.aubrun@chu-lyon.fr

Sponsor

Primary sponsor

Full Name
Hospices Civils De Lyon
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
NEFOPAM PANPHARMA 20 mg/2 mL, solution injectable/pour perfusion
Active Substance
NEFOPAM HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised
Starting Dose
20 mg/2 mL (product strength stated)
Investigational Product Name
Schweppes™
Modality
Other
Investigational Product Name
Morphine products (MORPHINE (CHLORHYDRATE) AGUETTANT 10 mg/mL; MORPHINE (SULFATE) LAVOISIER 50 mg/ml; MORPHINE (CHLORHYDRATE) AGUETTANT 0,1 mg/mL; MORPHINE (CHLORHYDRATE) LAVOISIER 20 mg/ml)
Active Substance
MORPHINE HYDROCHLORIDE / MORPHINE SULFATE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS BOLUS INJECTION/IV INFUSION / INJECTION
Authorisation Status
Authorised

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