Ultra-portable rapid-dispersal buccal lyophilised naloxone for constant carriage: testing in healthy volunteers
Opioid overdose
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 conditions in a random sequence. These five treatment arms are made up of three experimental IMPs. A novel rapid-dispersal ultra-portable formulation of naloxone at two test doses (2mg and 4mg) administered via buccal absorption in the cheek pouch, and a 2mg dose administered sublingually, and then two active comparator products; 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, equivalent to 2 mg of naloxone hydrochloride, per dose. The order in which a participant receives each IMP across five study visits is randomised via the King’s Clinical Trial Unit’s randomisation system, in which each treatment is assigned a code from 01-05, each participant will automatically be assigned a random order of code, representing the order of drug products for each visit, at the point of enrolment on the clinical study once eligible and confirmed. The time to reach maximum plasma concentration will be determined to characterise the rate of naloxone absorption. Tmax will be reported as the median and range for each treatment group, based on observations over the 4-hour post-dose period. This intensive sampling schedule, particularly in the first 15 minutes, is designed to accurately capture the early absorption phase and the precise determination of Tmax for each formulation and dose. Time to 50% of maximum concentration (T50%) A particularly important secondary endpoint will be the time taken to reach 50% of the observed Cmax, as the increase in plasma levels before reaching Cmax is unlikely to be linear, and the time taken to reach 50% with different formulations is likely to indicate the speed with which there may be a future benef
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.
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 <18 or >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