NCT06281951

Nebulized Fentanyl in Healthy Volunteers

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: University Hospital, Rouen · Academic / Other
• Sex: All
• Age: 18 Years – 68 Years
• Healthy volunteers: Accepted

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

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.

Conditions

• Analgesia
• Emergencies

Interventions

Type	Name	Description
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).
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

Timeline

• Start date: 2024-04-26
• Primary completion: 2026-03-01
• Completion: 2026-09-01
• First posted: 2024-02-28
• Last updated: 2025-04-15

Locations

1 site across 1 country: France