Pharmacodynamic Evaluation of Intranasal Nalmefene

Open-label, 2-part study. Part 1 is a pilot study to determine the relationship between opioid agonism and suppression of carbon dioxide induced increases in minute ventilation prior to opioid exposure. Part 2 will be a randomized, 2 period, 2 treatment, crossover study to evaluate the pharmacodynamic effects of intranasal (IN) nalmefene compared to IN naloxone to reverse opioid-induced suppression of carbon dioxide induced increases in minute ventilation, in healthy volunteers with prior opioid exposure.

Both Part 1 and Part 2 of the study will consist of an outpatient Screening Visit taking place 28 days prior to admission, an in-clinic Treatment Phase consisting of a 6 or 7 day inpatient stay, and a Follow-Up Phone Call conducted 3 to 7 days after discharge.

Inclusion criteria

• Male or female aged 18 to 55 years inclusive
• BMI ranging from 18 to 32 kg/m2, inclusive
• Adequate venous access
• Healthy subjects and non-dependent who are non dependent opioid experienced users, opioid experience defined as exposure to an opioid on at least 1 occasion prior to screening

Exclusion criteria

• History of clinically significant disease
• Significant trauma injury, major surgery, open biopsy within 30 days prior to screening
• Subject who has a difficult airway for intubation.
• Following an abnormal diet 4 weeks prior to screening
• Use of over-the-counter medications, dietary supplements, herbal products, vitamins or opioid analgesics 14 days before intervention
• Use of enzyme altering drugs 30 days before intervention
• Use of nasal products 28 days before intervention and throughout the study
• Previous or current opioid, alcohol, or other drug dependence
• Donated or received blood 30 days before intervention
• Women who are pregnant or breastfeeding at screening
• Women of childbearing potential unless surgically sterile or use effective contraception
• Current or recent upper respiratory tract infection
• Allergic to nalmefene or naloxone or known hypersensitivity reaction to plastics.