Pharmacokinetic Evaluation of Intranasal Nalmefene Using Three Dosing Regimens

Inclusion Criteria

• Male or female aged 18 to 55 years inclusive
• BMI ranging from 18 to 30 kg/m2, inclusive
• Adequate venous access
• Subjects must be non-smokers
• On screening and admission, the following standards had to be met before dosing and were permitted to be repeated once:
• Systolic blood pressure: 140 mmHg or less and equal to or greater than 90 mmHg
• Diastolic blood pressure: 90 mmHg or less and equal to or greater than 55 mmHg
• Heart rate: 100 beats per minute (bpm) or less and equal to or greater than 40 bpm
• Respiratory rate: 20 respirations per minute (rpm) or less and equal to or greater than 8 rpm

Exclusion Criteria

• History of clinically significant disease
• Significant trauma injury, major surgery, open biopsy within 30 days prior to screening
• Following an abnormal diet 4 weeks prior to screening
• Use of prescribed or over the counter medications, dietary supplements, herbal products, vitamins or opioid analgesics 14 days before intervention and throughout the study
• Use of enzyme altering drugs 30 days before intervention or during the study
• Use of nasal products 28 days before intervention and throughout the study
• Experimental agents used at least 8 weeks prior to initial dosing for a period equivalent to 5 half-lives of the agent (whichever was longer).
• Positive urine drug test for alcohol, opioids, cocaine, methamphetamine, benzodiazepines, tetrahydrocannabinol (THC), barbiturates, or methadone at screening or admission.
• Previous or current opioid, alcohol, or other drug dependence (excluding nicotine and caffeine)
• Positive urine screen for cotinine (smoking and the use of tobacco products were not permitted for 4 weeks prior to the first dose of study drug and throughout the duration of the study).
• An ECG QTcF interval >450 msec for males and > or equal to 470 msec for females.
• Clinically significant concurrent medical conditions
• Donated or received blood 30 days before intervention
• Women who are pregnant or breastfeeding at screening and prior to each administration of study drug
• Women of childbearing potential unless surgically sterile or use effective contraception
• Male subjects of childbearing potential that do not agree to use effective contraception
• Male subjects who plan to donate sperm or have female partner(s) who are pregnant, lactating or planning to attempt to become pregnant during the study or within 4 weeks after completion of the study
• Positive test for HBsAg, HCVAb, or HIVAb at screening
• Current or recent upper respiratory tract infection
• Current or recent use of any decongestants
• Allergic to nalmefene
• Those who would not abstain from engaging in strenuous exercise during the inpatient stay of the study.
• Those who would not abstain from consuming poppy seed or similar opium derived food stuff during the study.
• Those who would not abstain from ingesting alcohol, drinks containing xanthine >500 mg/day (e.g., Coca Cola®, coffee, tea, etc.), or grapefruit/grapefruit juice 72 hours before initial dosing and throughout the duration of the study.
• Those deemed unlikely to be able to comply with the requirements of the protocol.
• Those with any laboratory tests from samples taken at screening considered clinically significant.
• Those with a known intolerance to continuous ECG lead adhesive exposure.
• Brief Smell Identification Test (BSIT) score < 5 at screening.
• Those with a known hypersensitivity reaction to plastic.