Pharmacokinetics (PK) and Safety of Multiple Doses of Intranasal Naloxone in Healthy Adults

Phase 1

Completed

• Conditions: Opioid Overdose
• Interventions: Combination Product: 16 mg naloxone AP003; Combination Product: 8 mg naloxone NARCAN Nasal Spray

• Registration Number: NCT05377255
• Lead Sponsor: Emergent BioSolutions

Brief Summary

This study will be a Phase 1, single-center, open-label, randomized cross-over study to evaluate the PK of a new AP003 device which delivers two sprays of 4 mg naloxone hydrochloride intranasally.

Detailed Description

Based on the intended AP003 product presentation there will be two devices in each carton allowing for administration of a total of 16 mg. This study is designed for subjects to receive naloxone therapy either through the AP003 device or through the currently approved NARCAN® nasal spray (4 mg) device (per label), reference therapy. After administration of the therapy patients will be followed by a 48-hour washout period before treatment crossover. Key study parameters include safety and PK. Safety evaluations will include but not limited to complete and system directed physical examinations (including signs of nasal irritation such as erythema, edema, and erosion), administration of a Brief Smell Identification Test (B-SIT), assessments of vital signs, 12 lead electrocardiogram (ECG), continuous cardiac telemetry monitoring (CCT) , clinical laboratory tests (e.g., hematology, chemistry, urinalysis, pregnancy test), and evaluation of adverse events.

Study Timeline

• Study First Submitted: 2022-03-11
• Study Start: 2022-03-28
• Primary Completion: 2022-05-10
• Study Completion: 2022-05-10
• Study First Submitted QC: 2022-05-12
• Study First Posted: 2022-05-17
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-15
• Last Update Posted: 2024-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Are able to consent and freely provide informed consent.

• Females and males 18-55 years of age, inclusive.

• Have a body mass index (BMI) less than or equal to 34.0 kg/m2.

• Generally healthy, in the opinion of the Investigator, based on medical history, physical examination, vital signs, screening laboratory assessments and 12-lead ECG evaluation.

• If female:

  1. Have a negative pregnancy test at Screening (serum pregnancy test) and before dosing at Day -1 (urine pregnancy test)

  2. Female subjects of non-childbearing potential must be:

     • Post-menopausal (spontaneous amenorrhea for at least 12 months prior to dosing) with confirmation by documented FSH levels ≥40 mIU/mL; or
     • Surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy, or tubal ligation) at least 3 months prior to dosing.

  3. Women of childbearing potential who are not planning to be pregnant during the study period and who are using one of the following effective methods of contraception during the study period and for at least 30 days after last study visit:

     • Simultaneous use of hormonal contraceptive (e.g. oral, patch, depot injection, implant, vaginal ring, intrauterine device) or non-hormonal intrauterine device for at least 4 weeks prior to dosing (must agree to use the same contraceptive throughout the study) and condom for the male partner.
     • Simultaneous use of diaphragm or cervical cap with spermicide and condom for the male partner, started at least 21 days prior to dosing.

Exclusion Criteria

• Subjects planning to become pregnant during the study or currently breastfeeding.
• Any acute condition, in the opinion of the Investigator, that is not fully resolved at least 4 weeks prior to baseline.
• Subject has a deviated septum, previous rhinoplasty, abnormal nasal anatomy, other nasal symptoms (i.e., blocked and/or runny nose), or other nasal surgeries (i.e., polyp removal) within 1 year, or needs to use another nasal spray product during study.
• Subject with current upper respiratory infection (URI) or has had URI within 7 days prior to screening.
• Subject has had an episode of epistaxis within 30 days prior screening or has experienced recurrent episodes of epistaxis within 1 year prior to screening.
• Subject has used any prescription or nonprescription drugs/supplements with increased risk of bleeding within 28 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before the first dose of study drug with exception of oral contraceptives. All other prescription medications, over-the-counter, and natural health products within 14 days or 5 half-lives prior to the first dosing.
• Subject is currently participating in another clinical study of an investigational drug or has been dosed with any investigational drug within 30 days or 5 half-lives (whichever is longer) of the compound.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm 1 Interventional Therapy	16 mg naloxone AP003	Subjects will first receive 4 doses of 4 mg each (total: 16 mg) of naloxone through the AP003 device (Arm 1) before the washout period.
Arm 2 Reference Therapy	16 mg naloxone AP003	Subjects will first receive 2 doses of 4 mg each (total: 8 mg) of the naloxone through the NARCAN Nasal Spray device (reference therapy, Arm 2) before the washout period.
Arm 2 Reference Therapy	8 mg naloxone NARCAN Nasal Spray	Subjects will first receive 2 doses of 4 mg each (total: 8 mg) of the naloxone through the NARCAN Nasal Spray device (reference therapy, Arm 2) before the washout period.
Arm 1 Interventional Therapy	8 mg naloxone NARCAN Nasal Spray	Subjects will first receive 4 doses of 4 mg each (total: 16 mg) of naloxone through the AP003 device (Arm 1) before the washout period.

Primary Outcome Measures

Name	Time	Method
Mean naloxone plasma concentration Narcan dosing periods	PK samples taken at various timepoints over the course of Pre-dose and post-dose for 12 hours.	The mean naloxone plasma concentration during the two Narcan dosing periods.
Mean naloxone plasma concentration AP003 dosing periods.	PK samples taken at various timepoints over the course of Pre-dose and post-dose for 12 hours.	The mean naloxone plasma concentration during the two AP003 dosing periods.
Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAE)	Through end of study visit (within 7 days after second dose)	Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAE) by treatment thru End of Study Visit (within 7 days after 2nd dose).
Incidence of abnormal vital signs	Through end of study visit (within 7 days after second dose)	Incidence of abnormal vital signs (heart rate, blood pressure, and respiration rate) by treatment thru End of Study Visit (within 7 days after 2nd dose).
Incidence of clinically significant ECG	Through end of study visit (within 7 days after second dose)	Incidence of clinically significant ECG by treatment thru End of Study Visit (within 7 days after 2nd dose).
Incidence of changes in B-SIT assessment	Through end of study visit (within 7 days after second dose)	Incidence of changes in B-SIT assessment within an AP003 period thru End of Study Visit (within 7 days after 2nd dose).
Incidence of clinical laboratory changes	Through end of study visit (within 7 days after second dose)	Incidence of clinical laboratory changes by treatment thru End of Study Visit (within 7 days after 2nd dose).
Incidence of adverse events of special interest (AESI) indicating of nasal irritation	Through end of study visit (within 7 days after second dose)	Incidence of adverse events of special interest (AESI) indicating of nasal irritation (erythema, edema, and erosion) by treatment thru End of Study Visit (within 7 days after 2nd dose).

Trial Locations

Locations (1)

Syneos Health Clinical Research Services; 🇺🇸 Miami, Florida, United States