Multi-center study of a fentanyl nasal spray compared with placebo nasal spray for postoperative pain management.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CCDRD Cooperative Clinical Drug Research and Development AG, 5med GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

14 Apr 2024 → 10 Oct 2025

Decision date (initial)

2025-01-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

5med GmbH

External identifiers

EU CT number

2024-519625-38-00

EudraCT number

2018-001630-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

The primary objective of the present trial is the assessment of the efficacy of Fentanyl Nasal Spray in combination with an applicator as compared to placebo for the management of postoperative pain. Pain caused by orthopedic surgery will serve as a model for postoperative pain. Evidence from the literature will be used to bridge analgesic effectiveness of nasal fentanyl from pain primarily caused by activation of nociceptors to visceral pain (e.g. caused by abdominal surgery).

Secondary objectives 1

1. The secondary objective of the present trial is the assessment of the tolerability and side-effects of prolonged postoperative administration of Fentanyl Nasal Spray as compared with Standard of Care [morphine, applied by standard of care treatment via i.v. PCA (patient-controlled analgesia)]. Furthermore, the usability of the administration control device will be assessed.

Conditions and MedDRA coding

Postoperative pain relief

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female patients ≥18 years of age
2. Intended stay in a Post Anesthesia Care Unit (PACU) or recovery room unit for at least 120 minutes after orthopedic surgery performed using general anesthesia for one of the following procedures: - knee joint endoprosthesis surgery - isolated fracture of the femur, tibia, fibula, or calcaneus, treated by open reduction and internal fixation (ORIF)
3. American Society of Anesthesiology (ASA) physical status I, II, or III
4. Patients who are expected to develop acute moderate or severe pain expected to require parenteral opioids for at least 24 hours after surgery
5. Patients capable of handling the administration control device
6. Patients willing and able (e.g. mental and physical condition) to participate in all aspects of the study as evidenced by providing signed written informed consent

Exclusion criteria 25

1. History of hypersensitivity or intolerance to the active substance or any of the excipients of the study medication
2. Patients with respiratory depression, i.e. less than 10 breaths per minute
3. Patients with clinically significant obstructive airways disease, which is still symptomatic under stable treatment
4. Patients scheduled for post-operative analgesia supplied by a single-shot or continuous regional technique
5. Patients scheduled to receive non-steroidal anti-inflammatory drugs (NSAIDs) within 12 hours before surgery, immediately after operation, and during the first 24 hours after start of treatment with study medication
6. Patients scheduled to received local anesthetics in the surgical area
7. Patients expected to require another surgical procedure within 48 hours post-operatively
8. Patients who are expected to receive opioids other than fentanyl or sufentanil intra-operatively or fentanyl postoperatively
9. Known or suspected opioid tolerance or history of opioid dependence
10. Chronic treatment with opioids preoperatively on a fixed scheduled (regular) basis within 7 days before surgery
11. Chronic medication with gabapentine or pregabaline
12. Patients treated with medication that contains sodium oxybate
13. Patients with repeated episodes of epistaxis
14. Previous radiation therapy in the face area
15. Intake of MAO inhibitors within the last 14 days prior to randomization
16. Current anatomical abnormalities of the nose that is likely to interfere with the mucosal absorption of fentanyl via the nasal cavities
17. Severe common cold, intensive hay fever or any other circumstances requiring the use of congestive nasal sprays during the study period
18. Patient is currently enrolled in, or has completed less than 30 days before the screening examination of the present trial another clinical trial with an investigational drug
19. Previous enrolment in this study
20. Pregnant or breast-feeding women
21. Women of childbearing potential unable or unwilling to use highly effective contraceptive measures until start of hospitalization. Reliable methods for women are: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); - progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); - intrauterine device (IUD); - intrauterine hormone-releasing system (IUS); - bilateral tubal occlusion; - vasectomized partner; - sexual abstinence.
22. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study
23. Alcohol/drug dependence or abuse (excluding tobacco abuse)
24. Unreliability or lack of cooperation
25. Any other condition of the patient (e.g., serious or unstable medical or psychological condition, acute psychosis) that in the opinion of the investigator may compromise evaluation of the study treatment or may jeopardize patient’s safety, compliance or adherence to protocol requirements

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Survival distribution in the period from start of treatment with the first dose of the study medication until terminating the trial due to inadequate analgesia as required by the patient or felt necessary by the investigator within the first 24 hours after start of treatment with non-terminating patients censored at 24 hours.

Secondary endpoints 10

1. sum of ratings of pain intensity on a 11-point numeric rating scale at pre-defined points in time: at hours 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 after start of treatment (TotPaR)
2. sum of pain intensity difference ratings on a 11-point numeric rating scale comparing the pain rating before start of treatment (0) and ratings at pre-defined points in time (SPID): at hours 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, and 120 after start of treatment (Patients will not be woken up for a postoperative measurement. The last observation carried forward method will be used to replace a missing value
3. percentage of patients who terminate the study due to inadequate analgesia during the 24-hours treatment period
4. percentage of patients who terminate the study due to any reason during the 24-hours treatment period
5. number of actuations administered
6. number of unsuccessful actuations during lock-out period
7. patient's rating of usability [System Usability Scale (SUS)]
8. patient’s global rating of efficacy using a four-point Likert scale (poor, fair, good, or excellent)
9. investigator's global rating of efficacy (Likert scale: see above)
10. evaluation of ease of care (patients, nursing staff, and physiotherapists)

Investigational products

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

Test 1

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CCDRD Cooperative Clinical Drug Research and Development AG

Sponsor organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Address

Dahlwitz, Lindenallee 70, Dahlwitz-Hoppegarten Lindenallee 70 Dahlwitz-Hoppegarten

City

Hoppegarten

Postcode

15366

Country

Germany

Scientific contact point

Organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Contact name

Project Manager

Public contact point

Organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Contact name

Project Manager

Third parties 3

5med GmbH

Sponsor organisation

5med GmbH

Address

Lena-Christ-Strasse 2

City

Gruenwald

Postcode

82031

Country

Germany

Scientific contact point

Organisation

5med GmbH

Contact name

Managing Director: Dr. rer. med. Stefan Nardi-Hiebl

Public contact point

Organisation

5med GmbH

Contact name

Managing Director: Dr. rer. med. Stefan Nardi-Hiebl

Third parties 2

Locations

2 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 22 files

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

Application history

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