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

NCT05377255 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: EBS-NAR-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Overdose

Keywords

NARCAN; Opioid Overdose; Naloxone; Intranasal

Outcome Measures

Primary Outcomes (8)

• Mean naloxone plasma concentration AP003 dosing periods.

  The mean naloxone plasma concentration during the two AP003 dosing periods.

  PK samples taken at various timepoints over the course of Pre-dose and post-dose for 12 hours.

• Mean naloxone plasma concentration Narcan dosing periods

  The mean naloxone plasma concentration during the two Narcan dosing periods.

  PK samples taken at various timepoints over the course of Pre-dose and post-dose for 12 hours.

• Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAE)

  Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAE) by treatment thru End of Study Visit (within 7 days after 2nd dose).

  Through end of study visit (within 7 days after second dose)

• Incidence of abnormal vital signs

  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).

  Through end of study visit (within 7 days after second dose)

• Incidence of clinically significant ECG

  Incidence of clinically significant ECG by treatment thru End of Study Visit (within 7 days after 2nd dose).

  Through end of study visit (within 7 days after second dose)

• Incidence of clinical laboratory changes

  Incidence of clinical laboratory changes by treatment thru End of Study Visit (within 7 days after 2nd dose).

  Through end of study visit (within 7 days after second dose)

• Incidence of adverse events of special interest (AESI) indicating of nasal irritation

  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).

  Through end of study visit (within 7 days after second dose)

• Incidence of changes in B-SIT assessment

  Incidence of changes in B-SIT assessment within an AP003 period thru End of Study Visit (within 7 days after 2nd dose).

  Through end of study visit (within 7 days after second dose)

Study Arms (2)

Arm 1 Interventional Therapy

OTHER

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.

Combination Product: 16 mg naloxone AP003; Combination Product: 8 mg naloxone NARCAN Nasal Spray

Arm 2 Reference Therapy

OTHER

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.

Combination Product: 16 mg naloxone AP003; Combination Product: 8 mg naloxone NARCAN Nasal Spray

Interventions

8 mg naloxone NARCAN Nasal Spray COMBINATION_PRODUCT

2 doses of 4 mg each (total: 8 mg) of the naloxone through the NARCAN Nasal Spray device

Arm 1 Interventional Therapy; Arm 2 Reference Therapy

16 mg naloxone AP003 COMBINATION_PRODUCT

4 doses of 4 mg each (total: 16 mg) of naloxone through the AP003 device

Arm 1 Interventional Therapy; Arm 2 Reference Therapy

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Participants 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.
• Participant 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.
• Participant 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.
• Participant 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.
• Participant 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.
• Had a history of abuse or current misuse of illicit drugs, alcohol, or tobacco:
• alcohol abuse (regularly drinks more than 14 units of alcohol per week; 1 unit = 360 mL of beer, 150 mL of wine, or 45 mL of spirit \[40% a/v\]) or history of alcohol abuse within 6 months prior to Screening
• positive for recent alcohol use (by breathalyzer) at Screening or Baseline (Day -1)
• a history or evidence of abuse of licit or illicit drug substances or a positive urine drug screen (a urine sample was obtained for testing to determine the presence or absence of Schedule 1 or Schedule 2 typical drugs of abuse or their metabolites, including opioids, amphetamine derivatives, cocaine, and other analytes as needed) or drugs of abuse prior to Screening. History of cannabinoid use within 1 year prior to Screening or any current evidence of abuse.
• use of tobacco-containing products or had a history of tobacco use within 1 year prior to the screening visit
• use of e-cigarettes and/or nicotine replacement products or had used these products within 1 year prior to the screening visit.
• Participant who had consumed xanthine containing products (e.g., tea, coffee, cola), caffeine, within 24 hours of check-in. Participants had to refrain from ingesting these throughout the study
• History of severe allergic reaction or anaphylaxis to any component of the investigational product

Sponsors & Collaborators

• Emergent BioSolutions: lead

Study Sites (1)

Syneos Health Clinical Research Services

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Opiate Overdose

Condition Hierarchy (Ancestors)

Drug Overdose; Prescription Drug Misuse; Drug Misuse; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Narcotic-Related Disorders; Mental Disorders

Study Officials

• Nino Joy, MD

  Emergent BioSolutions

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: May 17, 2022
• Study Start: March 28, 2022
• Primary Completion: May 10, 2022
• Study Completion: May 10, 2022
• Last Updated: April 15, 2026

Record last verified: 2024-03

Locations

US (1)