Ignite Creation Date:
2025-12-24 @ 11:44 PM
Ignite Modification Date:
2025-12-25 @ 9:36 PM
Study NCT ID:
NCT06281951
Status:
RECRUITING
Last Update Posted:
2025-04-15
First Post:
2024-02-05
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Nebulized Fentanyl in Healthy Volunteers
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000377', 'term': 'Agnosia'}, {'id': 'D004630', 'term': 'Emergencies'}, {'id': 'D059787', 'term': 'Acute Pain'}], 'ancestors': [{'id': 'D010468', 'term': 'Perceptual Disorders'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D010146', 'term': 'Pain'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 20}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-04-26', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'completionDateStruct': {'date': '2026-09-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-04-11', 'studyFirstSubmitDate': '2024-02-05', 'studyFirstSubmitQcDate': '2024-02-20', 'lastUpdatePostDateStruct': {'date': '2025-04-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-02-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-03-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Measurement of [F] bioavailability via facial nebulization and intranasal inhalation.', 'timeFrame': '6 hours', 'description': 'Bioavailability \\[F\\] will be expressed as percent mean +/- standard deviation for each group.'}], 'secondaryOutcomes': [{'measure': 'Measurement of maximum decrease in PUAL (pupillary under ambient light) between facial nebulization and intranasal inhalation.', 'timeFrame': '6 hours', 'description': 'Maximum decrease in PUAL will be expressed as percent of baseline value +/- standard deviation for each group.'}, {'measure': 'Measurement of the difference between observed and predicted PUAL values by a PK/PD model.', 'timeFrame': '6 hours', 'description': 'The difference between observed and predicted values will be expressed as RMSE in percent.'}, {'measure': 'Time required to achieve >30% decrease in PUAL compared to baseline.', 'timeFrame': '6 hours', 'description': 'Time required for \\>30% decrease in PUAL will be expressed in minutes +/- standard deviation for each group.'}, {'measure': 'To assess respiratory tolerance', 'timeFrame': '8 hours', 'description': 'Using the respiratory rate and pulse oxygen saturation for respiratory tolerance'}, {'measure': 'To assess neurological tolerance', 'timeFrame': '8 hours', 'description': 'Using the Ramsay score for neurological tolerance'}, {'measure': 'To assess hemodynamic tolerance', 'timeFrame': '8 hours', 'description': 'Using the heart rate and blood pressure for hemodynamic tolerance'}, {'measure': 'Measurement of administration comfort score using a visual analog scale ranging from 0 (maximum discomfort) to 10 (optimal comfort) (unitless).', 'timeFrame': '6 hours', 'description': 'Administration comfort score will be expressed as mean +/- standard deviation for both groups.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Severe acute pain', 'Pharmacometry', 'Fentanyl', 'Emergency medicine', 'Pupillometry (PUAL)', 'Non-invasive analgesia (Intranasal, Facial aerosol)'], 'conditions': ['Analgesia', 'Emergencies']}, 'referencesModule': {'references': [{'pmid': '27663766', 'type': 'BACKGROUND', 'citation': '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': '21119516', 'type': 'BACKGROUND', 'citation': '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': '18606320', 'type': 'BACKGROUND', 'citation': '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': '35338897', 'type': 'BACKGROUND', 'citation': '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': '21867860', 'type': 'BACKGROUND', 'citation': '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': '28967529', 'type': 'BACKGROUND', 'citation': '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': '11927479', 'type': 'BACKGROUND', 'citation': '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': '40615143', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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', 'detailedDescription': '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.\n\nFacial 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.\n\nPupillometry, 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.\n\nPharmacometric 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '68 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years and \\< 68 years\n* BMI between 19 and 29 kg/m²\n* Affiliation to a social security scheme\n* Adult who has read and understood the information letter and signed the consent form\n* 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.\n* 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.\n\nExclusion Criteria:\n\n* Weight \\< 50 kg\n* Taking long-term painkillers or narcotics\n* Sharp pain\n* Stable chronic pain (\\>3 months, with or without long-term treatment)\n* Known chronic pathology stabilized or decompensated (hypertension, renal, cardiac, hepatic insufficiency, etc.)\n* Stable or decompensated chronic respiratory pathology\n* Chronic neuropsychiatric pathology likely to modify the pain threshold\n* Long-term treatment with an action on the nervous system such as respiratory depression: benzodiazepines, neuroleptics, agonist/antagonist of the opioid system\n* Treatment or toxicant whose association is not recommended with fentanyl (alcohol, cannabis, etc.)\n* Central nervous system modulator treatment\n* Pathologies blocking the pupillary response: Claude-Bernard-Horner syndrome, Adie syndrome, Argyll-Robertson pupil, senile miosis, dysautonomic neuropathy (advanced diabetes, systemic amyloidosis), cataract\n* Treatment responsible for fluctuation in PUAL measurements: parasympathetic modulators (clonidine, dexmedetomidine, droperidol, metoclopramide)\n* No-indication to FENTANYL PIRAMAL 100µg/2mL, solution for injection in ampoule\n* No-indication to PROAMP SODIUM CHLORIDE 0.9%, solution for injection\n* Ongoing treatment with nasal vasoconstrictors\n* Peripheral oxygen saturation less than 93%\n* Alteration of cognitive state: comprehension disorder, language disorder, memory disorder, confusion\n* Deaf or mute patient\n* Usual heart rate such as HR\\< 40 bpm and/or hypotension with systolic blood pressure SBP\\< 100 mm Hg\n* Atrioventricular block on ECG\n* History of cataract surgery\n* Confirmed or suspected covid 19 / active flu infection less than 15 days old\n* Allergy to plastic\n* Pregnant or parturient or breastfeeding woman or proven absence of contraception\n* Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection/under guardianship or curatorship\n* Person participating in research participating in another trial / having participated in another trial within 2 weeks\n* 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'}, 'identificationModule': {'nctId': 'NCT06281951', 'acronym': 'AEROfen', 'briefTitle': 'Nebulized Fentanyl in Healthy Volunteers', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Rouen'}, 'officialTitle': 'Nebulized Fentanyl in Healthy Volunteers : Comparison of Facial Versus Intranasal Aerosol Administration by Pharmacometric Modeling', 'orgStudyIdInfo': {'id': '2022/0271/HP'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Facial Nebulization', 'description': "Fentanyl's facial nebulization in healthy volunteers.", 'interventionNames': ['Drug: Fentanyl - Inhalation by facial nebulization']}, {'type': 'EXPERIMENTAL', 'label': 'Intranasal', 'description': "Fentanyl's intranasal inhalation in healthy volunteers.", 'interventionNames': ['Drug: Fentanyl - Nebulisation']}], 'interventions': [{'name': 'Fentanyl - Inhalation by facial nebulization', 'type': 'DRUG', 'otherNames': ['AEROGEN Nebulizer'], 'description': '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).', 'armGroupLabels': ['Facial Nebulization']}, {'name': 'Fentanyl - Nebulisation', 'type': 'DRUG', 'otherNames': ['Teleflex intranasal device'], 'description': '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', 'armGroupLabels': ['Intranasal']}]}, 'contactsLocationsModule': {'locations': [{'zip': '76031', 'city': 'Rouen', 'state': 'France', 'status': 'RECRUITING', 'country': 'France', 'facility': 'University Hospital, Rouen', 'geoPoint': {'lat': 49.44313, 'lon': 1.09932}}], 'centralContacts': [{'name': 'Cassandre Follet', 'role': 'CONTACT', 'email': 'cassandre.follet@chu-rouen.fr', 'phone': '+33232888990', 'phoneExt': '60451'}, {'name': 'Florian Vallin', 'role': 'CONTACT', 'email': 'florian.vallin@chu-rouen.fr', 'phone': '+3323288', 'phoneExt': '6697'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Rouen', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}