Pharmacokinetic study of the use of Nefopam 30 mg tablet in patients suffering from acute pain in rheumatology - NEFOPAIN kinetics

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Decision date (initial)

2025-09-24

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

Evaluate the pharmacokinetics of NEFOPAM PANPHARMA 30 mg, film-coated tablet versus NEFOPAM VIATRIS 20mg/ 2mL, injectable solution using a non-compartmental approach (NCA)

Secondary objectives 1

1. Develop a pharmacokinetic model using a population-based approach.

Conditions and MedDRA coding

Hospitalized patient with acute rheumatological pain, requiring nefopam if necessary

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Hospitalized rheumatology patient
2. Patient affiliated to or benefiting from a social security scheme
3. Patients with acute musculoskeletal pain
4. Estimated remaining hospital stay ≥ 4 days
5. NS ≥ 3
6. Age ≥ 18 years and ≤ 75 years
7. Patient has read and understood the information letter and signed the consent form
8. • Women o of childbearing age, defined by the CTCG as fertile women, after menarche and until menopause, except in cases of permanent infertility (including hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) o - using highly effective contraception according to the CTCG (combined hormonal contraception (estrogen and progesterone) associated with ovulation inhibition (oral, intravaginal, transdermal), hormonal contraception (progesterone only) associated with ovulation inhibition (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral fallopian tube occlusion, vasectomized partner, sexual abstinence) for at least 4 weeks prior to inclusion, during treatment, and up to 3 days after the last dose/administration of treatment, - and having a negative urinary pregnancy test for β-HCG at inclusion. o Menopausal: Menopause, according to the CTCG, is defined as the absence of menstruation for 12 months without any other medical cause. Elevated follicle-stimulating hormone (FSH) levels in the postmenopausal interval can be used to confirm postmenopausal status in women who are not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

Exclusion criteria 13

1. Patients receiving nefopam within 7 days of inclusion
2. Pregnant, parturient or breast-feeding women, or those without proven contraception
3. Person deprived of liberty by an administrative or judicial decision or person placed under safeguard of justice / sub-guardianship or curatorship
4. Patients with creatinine clearance ≤ 30 ml/min according to the CKD-EPI formula
5. Patient treated with drug(s) containing alcohol as excipient
6. Severe or uncontrolled cardiovascular disease.
7. Patients treated with an enzyme inducer or inhibitor (Amiodarone, Bupropion, Fluoxetine, Paroxetine, Quinidine, Venlafaxine, Haloperidol, Imipramine, Tamoxifen, Ketoconazole, Ritonavir, Clarithromycin, Carbamazepine, St. John's Wort, Itraconazole, Rifampicin, Dexamethasone)
8. Patients with severe hepatic impairment (ASAT and/or ALAT > 5 times the upper normal)
9. History of psychological or sensory illness or abnormality likely to prevent the subject from fully understanding the conditions required for participation in the protocol or from giving informed consent
10. Patient unable to understand pain scales
11. Medical contraindication to NEFOPAM VIATRIS 20 mg/2 mL, solution for injection or NEFOPAM PANPHARMA 30 mg, film-coated tablet: o Hypersensitivity to nefopam or any of its excipients. o Convulsions or history of convulsive disorders. o Risk of urinary retention due to urethroprostatic disorders. o Risk of angle-closure glaucoma.
12. Patient suffering from constipation
13. Patient with a history of substance use disorders

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. main PK parameters will be determined using PKAnalix 2024R1 software (MonolixSuite, Saclay, France). They will include terminal elimination half-life, maximum concentration (Cmax), time at maximum concentration (Tmax) and exposure, characterized by the area under the curve obtained using the trapezoidal method. Bbioavailability will be calculated as the ratio of the AUC between the oral and intravenous forms, normalized to the dose for each patient using the cross-over design

Secondary endpoints 1

1. volume of distribution (Vd), maximum plasma concentration of the PO form (Cmax), time after intake for which the concentration is maximum (Tmax), terminal elimination half-life and bioavailability, and to highlight potential clinico-biological factors responsible for a variation in exposure. The flexibility of the modeling will then enable different doses to be simulated to determine the optimal dosages maximizing likelihood with the IV route.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications