Opioid overdose Injury, Occupational Diseases, Poisoning
Conditions
Interventions
This study will employ an open-label, within-subject design with repeated sessions to evaluate the IMPs in a five-way crossover design, where each participant will receive all the considered treatment
intramuscular naloxone via naloxone ampoule which contains 0.4mg/1ml naloxone hydrochloride, and an intranasal spray formulation (Nyxoid), containing 1.8mg/0.1ml naloxone hydrochloride dihydrate, equi
Sponsors
Kings Health Partners
King's College London
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Healthy volunteers. Defined as healthy based on medical examination, which includes: clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. 2. Aged 18-60 3. Able and willing to provide written informed consent 4. Adequate venous access and willingness for intravenous cannulation during each visit.
Exclusion criteria
Exclusion criteria: 1. Clinically relevant medical history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the participant. 2. Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer’s participation in the trial or make it unnecessarily hazardous. 3. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any neurological or mental illness. 4. Surgery or medical condition that might affect the absorption of medicines. 5. Blood pressure and heart rate in the supine position at the screening examination outside the ranges: blood pressure 90–140 mm Hg systolic, 40–90 mm Hg diastolic; heart rate 40–100 beats/min. Repeat measurements are permitted if values are borderline (i.e. values that are within 5 mm Hg for blood pressure or 5 beats/min for heart rate) or if requested by the investigator. Subjects can be included if the repeat value is within range or still borderline but deemed not clinically significant by the investigator. 6. Loss of more than 400 mL of blood during the 3 months before the trial, e.g. as a blood donor. 7. Any prescribed medication (apart from contraceptives). 8. Use of any over-the-counter medications containing codeine or other opioids, prescribed opioid medication, or illicitly obtained opioids within the past 2 weeks (if the participant is taking a long-acting opioid, the period might, after consideration by the examining doctor, be extended to 4 weeks or longer according to the washout period). 9. BMI 30.0kg/m2. 10. Intake of more than 14 units of alcohol weekly. 11. Pregnant or breastfeeding. 12. Women of childbearing potential (as defined in CTFG guidelines, see 6.7 Concomitant Medication) not willing to use a highly effective form of contraception (as defined in CTFG guidelines, see section 6.7 Concomitant Medication) during participation in the study or male patients not willing to ensure the use of a condom during participation in the study. 13. eGFR= 70 ml/min. 14. Any liver function or renal function test abnormality. A repeat is allowed on one occasion for the determination of eligibility. 15. Urine drug screen positive for any substances. 16. Positive alcohol breath test, above 0. 17. Participant in any other clinical trial or experimental drug study in the past 3 months 18. Known hypersensitivity to naloxone and/or formulation excipients (gelatin, mannitol). 19. Not willing to ingest fish-derived gelatin. 20. Insufficient understanding of the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to Maximum Plasma Concentration (Tmax) will be determined from blood samples collected at multiple timepoints over 4 hours following administration of each naloxone formulation. Blood samples will be collected pre-dose and at 2, 4, 6, 8, 10, 12.5, 15, 30, 45 minutes and 1, 1.5, 2, and 4 hours post-dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| The following secondary outcome measures will be evaluated from the same series of blood samples collected for the primary endpoint: pre-dose and at 2, 4, 6, 8, 10, 12.5, 15, 30, 45 minutes and 1, 1.5, 2, and 4 hours after administration, unless otherwise stated: 1. Time to 50% of maximum concentration (T50%) 2. Maximum Plasma Concentration (Cmax) 3. Area Under the Curve from time zero to infinity (AUCinf) 4. Area Under the Curve from time zero to 15 minutes (AUC0-15) 5. Elimination Half-life (t1/2) 6. Wafer disintegration time will be measured immediately after administration 7. Taste and tolerability will be measured using a Visual Analogue Scale (VAS) immediately following administration of each formulation | — |
Countries
England, United Kingdom
Contacts
Public ContactCraig Macpherson
Outcome results
None listed