Nebulized Fentanyl in Healthy Volunteers

NCT06281951 | Recruiting Phase 1

• 1 other identifier: 2022/0271/HP
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Pain constitutes the predominant motive prompting individuals to seek emergency medical attention, accounting for 80% of admissions to emergency departments. Presently, it is imperative to employ expeditious and efficacious analgesia-sedation methodologies, obviating the necessity for intravenous administration, while ensuring the secure delivery of pharmaceutical agents. The objective of this study is to assess the feasibility and comfort of nebulized intranasal or facial aerosol administration of Fentanyl through the implementation of a pharmacokinetic/pharmacodynamic (PK/PD) study

Conditions

Analgesia; Emergencies

Keywords

Severe acute pain; Pharmacometry; Fentanyl; Emergency medicine; Pupillometry (PUAL); Non-invasive analgesia (Intranasal, Facial aerosol)

Outcome Measures

Primary Outcomes (1)

• Measurement of [F] bioavailability via facial nebulization and intranasal inhalation.

  Bioavailability \[F\] will be expressed as percent mean +/- standard deviation for each group.

  6 hours

Secondary Outcomes (7)

• Measurement of maximum decrease in PUAL (pupillary under ambient light) between facial nebulization and intranasal inhalation.

  6 hours

• Measurement of the difference between observed and predicted PUAL values by a PK/PD model.

  6 hours

• Time required to achieve >30% decrease in PUAL compared to baseline.

  6 hours

• To assess respiratory tolerance

  8 hours

• To assess neurological tolerance

  8 hours

Study Arms (2)

Facial Nebulization

EXPERIMENTAL

Fentanyl's facial nebulization in healthy volunteers.

Drug: Fentanyl - Inhalation by facial nebulization

Intranasal

EXPERIMENTAL

Fentanyl's intranasal inhalation in healthy volunteers.

Drug: Fentanyl - Nebulisation

Interventions

Fentanyl - Inhalation by facial nebulization DRUG

3 administrations based on a weight-dependent threshold (40 µg per administration for a weight \< 70kg and 50 µg per administration for a weight ≥ 70kg).

Also known as: AEROGEN Nebulizer

Facial Nebulization

Fentanyl - Nebulisation DRUG

3 administrations based on a weight-dependent threshold (20 µg/administration and for a weight \< 70kg and 30 µg/administration for a weight ≥ 70kg). The dose of each bolus will be distributed at equivalent volume in both nasal pits

Also known as: Teleflex intranasal device

Intranasal

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and \< 68 years
• BMI between 19 and 29 kg/m²
• Affiliation to a social security scheme
• Adult who has read and understood the information letter and signed the consent form
• Woman definitely surgically sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy). Postmenopausal woman: The postmenopausal state is defined by the absence of periods for 12 months without any other medical cause.

You may not qualify if:

• Weight \< 50 kg
• Taking long-term painkillers or narcotics
• Sharp pain
• Stable chronic pain (\>3 months, with or without long-term treatment)
• Known chronic pathology stabilized or decompensated (hypertension, renal, cardiac, hepatic insufficiency, etc.)
• Stable or decompensated chronic respiratory pathology
• Chronic neuropsychiatric pathology likely to modify the pain threshold
• Long-term treatment with an action on the nervous system such as respiratory depression: benzodiazepines, neuroleptics, agonist/antagonist of the opioid system
• Treatment or toxicant whose association is not recommended with fentanyl (alcohol, cannabis, etc.)
• Central nervous system modulator treatment
• Pathologies blocking the pupillary response: Claude-Bernard-Horner syndrome, Adie syndrome, Argyll-Robertson pupil, senile miosis, dysautonomic neuropathy (advanced diabetes, systemic amyloidosis), cataract
• Treatment responsible for fluctuation in PUAL measurements: parasympathetic modulators (clonidine, dexmedetomidine, droperidol, metoclopramide)
• No-indication to FENTANYL PIRAMAL 100µg/2mL, solution for injection in ampoule
• No-indication to PROAMP SODIUM CHLORIDE 0.9%, solution for injection
• Ongoing treatment with nasal vasoconstrictors

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

University Hospital, Rouen

Rouen, France, 76031, France

RECRUITING

Related Publications (8)

• Barksdale AN, Hackman JL, Williams K, Gratton MC. ED triage pain protocol reduces time to receiving analgesics in patients with painful conditions. Am J Emerg Med. 2016 Dec;34(12):2362-2366. doi: 10.1016/j.ajem.2016.08.051. Epub 2016 Aug 27.

  PMID: 27663766 BACKGROUND

• Gueant S, Taleb A, Borel-Kuhner J, Cauterman M, Raphael M, Nathan G, Ricard-Hibon A. Quality of pain management in the emergency department: results of a multicentre prospective study. Eur J Anaesthesiol. 2011 Feb;28(2):97-105. doi: 10.1097/EJA.0b013e3283418fb0.

  PMID: 21119516 BACKGROUND

• Lvovschi V, Aubrun F, Bonnet P, Bouchara A, Bendahou M, Humbert B, Hausfater P, Riou B. Intravenous morphine titration to treat severe pain in the ED. Am J Emerg Med. 2008 Jul;26(6):676-82. doi: 10.1016/j.ajem.2007.10.025.

  PMID: 18606320 BACKGROUND

• Galinski M, Robledo JB, Tellier E, Catoire P, De La Riviere C, Lvovschi V, Gil-Jardine C. Are Patients with Chronic Pain Less Satisfied with Their ED Management Than Non-Chronic Pain Patients? Am J Emerg Med. 2022 Jun;56:7-9. doi: 10.1016/j.ajem.2022.03.032. Epub 2022 Mar 19. No abstract available.

  PMID: 35338897 BACKGROUND

• Mudd S. Intranasal fentanyl for pain management in children: a systematic review of the literature. J Pediatr Health Care. 2011 Sep-Oct;25(5):316-22. doi: 10.1016/j.pedhc.2010.04.011. Epub 2010 Jun 17.

  PMID: 21867860 BACKGROUND

• Adelgais KM, Brent A, Wathen J, Tong S, Massanari D, Deakyne S, Sills MR. Intranasal Fentanyl and Quality of Pediatric Acute Care. J Emerg Med. 2017 Nov;53(5):607-615.e2. doi: 10.1016/j.jemermed.2017.05.027. Epub 2017 Sep 28.

  PMID: 28967529 BACKGROUND

• Hudson RJ, Thomson IR, Henderson BT, Singh K, Harding G, Peterson DJ. Validation of fentanyl pharmacokinetics in patients undergoing coronary artery bypass grafting. Can J Anaesth. 2002 Apr;49(4):388-92. doi: 10.1007/BF03017328.

  PMID: 11927479 BACKGROUND

• Follet C, Dumont A, Roussel M, Gillibert A, Boedard C, Quillard M, Ruault S, Vallin F, Donnadieu N, Nunes Ferreira D, Pereira T, Joly LM, Lvovschi V, Duflot T. AEROfen: protocol for a phase I, open-label, randomised crossover study evaluating the efficiency of nebulised fentanyl in healthy volunteers - comparing facial versus intranasal administration via pharmacometric modelling. BMJ Open. 2025 Jul 3;15(7):e091125. doi: 10.1136/bmjopen-2024-091125.

  PMID: 40615143 DERIVED

MeSH Terms

Conditions

Agnosia; Emergencies; Acute Pain

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes; Pain

Central Study Contacts

Cassandre Follet

CONTACT

+33232888990; cassandre.follet@chu-rouen.fr

Florian Vallin

CONTACT

+3323288; florian.vallin@chu-rouen.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 28, 2024
• Study Start: April 26, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 11, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)