To compare the plasma concentration (bioavailability) and safety of a single naloxone 5 mg autoinjector intramuscular (IM) injection to a single 2 mg IM injection (an approved safe dose) and to a single 2 mg bolus intravenous (IV) injection (an approved safe dose)
A randomized, open-label, 3-treatment, 6-sequences, 3-period Williams Square crossover single-dose, relative bioavailability study in healthy adult participants. The study includes Screening period, a Treatment period and a Follow-up contact (SoA). At least twelve (12) participants will be enrolled. If the number of evaluable participants falls below 12, participants may be replaced.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
13
5 mg (5 mg/0.5 mL) IM autoinjector injection into lateral thigh
2 mg IM (2mg/2 mL) injection into gluteal muscle
2 mg bolus IV (2mg/2 mL)
New Haven Clinical Research Unit
New Haven, Connecticut, United States
Maximum observed plasma naloxone concentration (Cmax) of a single 5 mg IM autoinjector injection compared to a 2 mg IM injection
Comparison of bioavailability
Time frame: predose, 2.5, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1440 minutes after dose
Area under the naloxone concentration versus time curve (AUC) from time zero to the last collection time (AUClast) of a single 5 mg IM autoinjector injection compared to a 2 mg IM injection
Comparison of bioavailability
Time frame: predose, 2.5, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1440 minutes after dose
AUC from time zero to 2.5 minutes (AUC0-2.5)
Pharmacokinetics all treatment arms
Time frame: predose and 2.5 minutes after dose
AUC from time zero to 5 minutes (AUC0-5)
Pharmacokinetics all treatment arms
Time frame: predose, 2.5 and 5 minutes after dose
AUC from time zero to 15 minutes (AUC0-15)
Pharmacokinetics all treatment arms
Time frame: predose, 2.5, 5, 10 and 15 minutes after dose
AUC from time zero to 30 minutes (AUC0-30)
Pharmacokinetics all treatment arms
Time frame: predose, 2.5, 5, 10, 15, and 30 minutes after dose
AUC from time zero extrapolated to infinity (AUCinf) [if data permit]
Pharmacokinetics all treatment arms
Time frame: predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
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Time to maximum observed naloxone plasma concentration (Tmax) [if data permit],
Pharmacokinetics all treatment arms
Time frame: predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Time for naloxone plasma concentration to decrease by one half (t1/2) [if data permit].
Pharmacokinetics all treatment arms
Time frame: predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Number of participants with a clinically significant change from baseline physical examination
Safety and tolerability all treatments
Time frame: baseline to 28 days after last dose
Number of participants with a clinically significant change from baseline vital signs
Safety and tolerability all treatments
Time frame: baseline to 28 days after last dose
Number of participants with a clinically significant change from baseline clinical safety laboratory measurements
Safety and tolerability all treatment arms
Time frame: baseline to 28 days after last dose
Number of participants with clinically significant AEs from baseline
Safety and tolerability all treatment arms
Time frame: baseline to 28 days after last dose