study of single and multiple doses of inhaled aerolef (liposome-encapsulated fentanyl)in healthy subjects

Conditions: Healthy

Summary: this study was designed to assess single-dose and multiple-dose pk and safety parameters utilizing a dosage of 3 ml (500 µg/ml)aerolef delivered via nebulization with the aeroeclipse ban device. the study was conducted in opioid naïve subjects who were not blocked with naloxone or other opioid receptor antagonists.

period i: subjects received an i.v.dose of fentanyl (200 µg) (treatment a). period ii: subjects were randomly assigned to receive either a single-dose (treatment b) or multi-dose (treatment c) of aerolef. in the multi-dose treatment c group, subjects received a dose of 3 ml aerolef every 12 hours for a total of five doses over a 3 days with a 4 week washout period before crossing over to period iii. period iii: subjects from period ii participated in the crossover study and receive either a multi-dose (treatment c, 5 doses at 12 hour intervals) or a single dose (treatment b). subjects in treatment b or treatment c were instructed to continue inhalation of aerolef for approximately one (1) minute beyond the point of nebulizer sputter to ensure that all aerosolized medication was delivered.

Eligibility criteria:
inclusion criteria: * non-smoking male or female with a minimum age of at least 18 years * body weight with abmi range of 18.5 - 27, with a minimum weight of at least 60 kg. * availability of subject for the entire study period and willingness to adhere to protocol requirements, as evidenced by a signed, written, informed consent form. * normal findings in the physical examination, vital signs (blood pressure between 100-140 - 60-90 mmhg, heart rate between 55-99 beats/min, respiration rate between 12-20 minute) and a 12 lead ecg. * negative for drug abuse, nicotine, alcohol, hepatitis b-surface antigen, hepatitis c and hiv. * if a female of child-bearing potential, the patient must have a negative urine pregnancy test at screening and baseline. * no clinical laboratory values outside of the principal investigator's acceptable range, unless the principal investigator decided that the subject's values are not clinically significant. * female subjects: (a) if pre-menopausal, have regular menstrual cycles (28-32 days), and (b) are not pregnant prior to study start and avoids pregnancy during the study and 1 month post drug administration, or (c) were surgically sterile for at least 6 months prior to enrollment, or (d) are post-menopausal for at least 1 year prior to enrollment. exclusion criteria: * known history of hypersensitivity to fentanyl. * presence or history of cardiac, pulmonary, gastrointestinal, endocrine, neuromuscular, neurologic, hematological, liver or kidney disease, or any condition known to interfere with absorption, distribution , metabolism, or excretion of drugs. * history of drug abuse or narcotic dependency. * use of prescription medication within 30 days preceding entry int the study, including any enzyme inducing/inhibitory drugs (excluding contraceptives). * participating in a clinical trial with an investigational drug within 30 days preceding this trial. * blood donation within 45 days preceding this trial.

Keywords: aerolef fentanyl pharmacokinetics liposome encapsulated