Nebulized Fentanyl in Healthy Volunteers (AEROfen)

May 6, 2026 updated by: University Hospital, Rouen

Nebulized Fentanyl in Healthy Volunteers : Comparison of Facial Versus Intranasal Aerosol Administration by Pharmacometric Modeling

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The prompt identification, assessment, and management of pain are imperative in the context of emergency medicine, necessitating rapid and effective interventions. In the realm of pain management, the investigators deemed it crucial to concentrate on non-invasive approaches, such as opioid nebulization, while ensuring the safe and controlled delivery of the pharmaceutical agent. Intranasal analgesia emerges as a particularly suitable option due to its non-invasiveness, painlessness, ease of administration, cost-effectiveness, and lack of stringent aseptic requirements, making it especially convenient for patients in pain. However, the administration of medications in nasal drop form lacks precise control over the quantity of the active drug, potentially resulting in a hepatic first-pass effect and inactivation before systemic absorption, particularly with large quantities and subsequent swallowing.

Facial nebulization of opiates presents an alternative method for analgesic administration. Traditional pneumatic nebulizers, readily available in emergency settings, are economical aerosol generators. However, they pose challenges related to the reproducibility of administration and the potential for infectious contamination due to the dispersion of nebulized particles in the air between inhalations. Palladium vibrating screen aerosols, designed to produce optimal particle sizes for drug delivery to the lungs, show promise due to their more occlusive system, offering enhanced performance. Yet, these devices lack evaluation in the realm of opioids, particularly in terms of objective nociception measurement.

Pupillometry, specifically PUAL (pupillary unrest in ambient light), stands out as an objective technique capable of quantifying nociception or opioid impregnation. PUAL monitors variations in pupil diameter over time, and previous studies have indicated an inverse correlation between the analgesic response to opioid treatment and PUAL amplitude, suggesting it could serve as a marker of central opioid impregnation. However, scientific evidence in alert emergency medicine patients remains lacking. Additionally, standard clinical pharmacodynamic evaluation criteria for opioids are not well-suited to the variability of therapeutic responses in emergency situations.

Pharmacometric models offer a quantitative approach to understanding relationships between administered drugs, clinico-biological covariates, exposure, and responses (biomarkers, efficacy, safety) as they evolve over time in individual patients and populations. This pilot study aims to evaluate the feasibility, safety, effects, and robustness of nebulized fentanyl administration via facial aerosol or intranasal routes in a population of adult healthy volunteers, employing equivalent analgesic doses. PUAL will serve as an objective pharmacodynamic marker of central opioid impregnation, coupled with pharmacokinetic modeling of nebulized fentanyl administered via facial aerosol or intranasally. The development of a pharmacometric model using a population-based approach aims to establish fentanyl titration strategies based on the objective of reducing PUAL while ensuring central opioid impregnation.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
    • France
      • Rouen, France, France, 76031
        • Recruiting
        • University Hospital, Rouen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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 capable of procreating (a woman is considered capable of procreating, i.e. fertile, after menarche and until she becomes menopausal, unless she is definitely sterile ) having very effective contraception (combined hormonal contraception (containing estrogens and progestins) associated with inhibition of ovulation, progestin-only hormonal contraception associated with inhibition of ovulation, intrauterine device, hormone-releasing intrauterine system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence) for 1 year and a negative urine pregnancy test at inclusion and during the duration of the study.
  • 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.

Exclusion Criteria:

  • 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
  • Peripheral oxygen saturation less than 93%
  • Alteration of cognitive state: comprehension disorder, language disorder, memory disorder, confusion
  • Deaf or mute patient
  • Usual heart rate such as HR< 40 bpm and/or hypotension with systolic blood pressure SBP< 100 mm Hg
  • Atrioventricular block on ECG
  • History of cataract surgery
  • Confirmed or suspected covid 19 / active flu infection less than 15 days old
  • Allergy to plastic
  • Pregnant or parturient or breastfeeding woman or proven absence of contraception
  • Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection/under guardianship or curatorship
  • Person participating in research participating in another trial / having participated in another trial within 2 weeks
  • History of illness or psychological or sensory abnormality likely to prevent the subject from fully understanding the conditions required for participation in the protocol or preventing them from giving informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Facial Nebulization
Fentanyl's facial nebulization in healthy volunteers.
Drug: Fentanyl - Inhalation by facial nebulization
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).
Other Names:
  • AEROGEN Nebulizer
Experimental: Intranasal
Fentanyl's intranasal inhalation in healthy volunteers.
Drug: Fentanyl - Nebulisation
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
Other Names:
  • Teleflex intranasal device

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of [F] bioavailability via facial nebulization and intranasal inhalation.
Time Frame: 6 hours
Bioavailability [F] will be expressed as percent mean +/- standard deviation for each group.
6 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time required to achieve >30% decrease in PUAL compared to baseline.
Time Frame: 6 hours
Time required for >30% decrease in PUAL will be expressed in minutes +/- standard deviation for each group.
6 hours
Measurement of administration comfort score using a visual analog scale ranging from 0 (maximum discomfort) to 10 (optimal comfort) (unitless).
Time Frame: 6 hours
Administration comfort score will be expressed as mean +/- standard deviation for both groups.
6 hours
Measurement of maximum decrease in PUAL (pupillary under ambient light) between facial nebulization and intranasal inhalation.
Time Frame: 6 hours
Maximum decrease in PUAL will be expressed as percent of baseline value +/- standard deviation for each group.
6 hours
Measurement of the difference between observed and predicted PUAL values by a PK/PD model.
Time Frame: 6 hours
The difference between observed and predicted values will be expressed as RMSE in percent.
6 hours
To assess respiratory tolerance
Time Frame: 8 hours
Using the respiratory rate and pulse oxygen saturation for respiratory tolerance
8 hours
To assess neurological tolerance
Time Frame: 8 hours
Using the Ramsay score for neurological tolerance
8 hours
To assess hemodynamic tolerance
Time Frame: 8 hours
Using the heart rate and blood pressure for hemodynamic tolerance
8 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Rouen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2024

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

February 5, 2024

First Submitted That Met QC Criteria

February 20, 2024

First Posted (Actual)

February 28, 2024

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022/0271/HP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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