Opioid OverdosePhase 1NCT05377255
Pharmacokinetics (PK) and Safety of Multiple Doses of Intranasal Naloxone in Healthy Adults
A Phase 1 study testing 16 mg naloxone AP003 and 8 mg naloxone NARCAN Nasal Spray in people with Opioid Overdose, run by Emergent BioSolutions at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid Overdose
- What is being tested?
- 16 mg naloxone AP003 and 8 mg naloxone NARCAN Nasal Spray
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2022to 10 May 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
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- 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
- Participant had a positive test result at Screening for human immunodeficiency virus (HIV) 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen
- Participant was unable or unwilling to undergo venipuncture for blood sample collection because of poor tolerability or unlikely to complete the trial due to poor venous access
- Participant who had donated plasma or whole blood within 30 days and 60 days, respectively, prior to dosing
- On standard 12-lead ECG, a corrected QT interval using the Fredericia formula (QTcF) interval >450 msec for males and females. If a single ECG QTcF is >450, two more ECGs were obtained over a 5-10 min period and the average of the QTcF interval from the 3 ECGs readings were to be used to determine eligibility
- Planned medical or surgical procedure that could have adversely impact the participant's participation or the conduct of the study
- Any disease, including serious medical or psychiatric condition and/or clinically significant abnormality of laboratory parameters and/or any other reason, which in the opinion of the Investigator and/or medical monitor (MM) compromised the safety of the participant or integrity of the study, interfered with the participant participation in the trial, or compromised the trial objectives
- Participant had a B-SIT score outside of the normative range (10-12) at screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
Syneos Health Clinical Research Services
Miami, Florida, 33136
About this study
Official title: A Phase 1, Open Label, Randomized Study to Investigate the Pharmacokinetics and Safety of Multiple Doses of Intranasal Naloxone in Healthy Adult Participants
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.
Read the 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.
- Conditions
- Opioid Overdose
- Being tested
- 16 mg naloxone AP003, 8 mg naloxone NARCAN Nasal Spray
- Keywords
- NARCAN, Opioid Overdose, Naloxone, Intranasal
- Medical subject headings
- Opiate Overdose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
16 mg naloxone AP003Combination product
4 doses of 4 mg each (total: 16 mg) of naloxone through the AP003 device
8 mg naloxone NARCAN Nasal SprayCombination product
2 doses of 4 mg each (total: 8 mg) of the naloxone through the NARCAN Nasal Spray device
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Combination Product: 16 mg naloxone AP003; Combination Product: 8 mg naloxone NARCAN Nasal Spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean naloxone plasma concentration AP003 dosing periods.
The mean naloxone plasma concentration during the two AP003 dosing periods.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: Through end of study visit (within 7 days after second dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start28 Mar 2022
- Primary completion10 May 2022
- Study completion10 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid OverdoseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emergent BioSolutions
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nino Joy, MD, Study director, Emergent BioSolutions
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05377255
- Sponsor's protocol ID
- EBS-NAR-001
- Status last verified
- Aug 2026
- First submitted
- 11 Mar 2022
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cassie D, Warnock B, Akhtar F, McCloskey D, Wyatt D. A Phase 1, Open-Label, Randomized Study to Investigate the Pharmacokinetics and Safety of Multiple Doses of Intranasal Naloxone in Healthy Participants. Clin Transl Sci. 2026 Jul;19(7):e70640. doi: 10.1111/cts.70640.
PubMed 42332351
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open Label, Randomized Study to Investigate the Pharmacokinetics and Safety of Multiple Doses of Intranasal Naloxone in Healthy Adult Participants
- ClinicalTrials.gov ID
- NCT05377255
- Acronym / sponsor ID
- EBS-NAR-001
- Conditions
- Opioid Overdose
- Keywords
- NARCAN, Opioid Overdose, Naloxone, Intranasal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Emergent BioSolutionsIndustry (pharma, biotech, devices)
- Study start
- 28 Mar 2022 (actual)
- Primary completion
- 10 May 2022 (actual)
- Study completion
- 10 May 2022 (actual)
- First posted
- 17 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Interventional Therapy | Other | Combination Product: 16 mg naloxone AP003, Combination Product: 8 mg naloxone NARCAN Nasal SpraySubjects 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 | Other | Combination Product: 16 mg naloxone AP003, Combination Product: 8 mg naloxone NARCAN Nasal SpraySubjects 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 16 mg naloxone AP0034 doses of 4 mg each (total: 16 mg) of naloxone through the AP003 device | Combination product | Arm 1 Interventional Therapy, Arm 2 Reference Therapy |
| 8 mg naloxone NARCAN Nasal Spray2 doses of 4 mg each (total: 8 mg) of the naloxone through the NARCAN Nasal Spray device | Combination product | Arm 1 Interventional Therapy, Arm 2 Reference Therapy |
Primary outcome
Mean naloxone plasma concentration AP003 dosing periods.
Time frame: 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.
Mean naloxone plasma concentration Narcan dosing periods
Time frame: 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.
Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAE)
Time frame: 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
Time frame: 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
Time frame: 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 clinical laboratory changes
Time frame: 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
Time frame: 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).
Incidence of changes in B-SIT assessment
Time frame: 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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Results publication: PubMed 42332351Cassie D, Warnock B, Akhtar F, McCloskey D, Wyatt D. A Phase 1, Open-Label, Randomized Study to Investigate the Pharmacokinetics and Safety of Multiple Doses of Intranasal Naloxone in Healthy Participants. Clin Transl Sci. 2026 Jul;19(7):e70640. doi: 10.1111/cts.70640.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nino Joy, MD study director
Emergent BioSolutions
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 16 mg naloxone AP003 and 8 mg naloxone NARCAN Nasal Spray in people with Opioid Overdose, run by Emergent BioSolutions at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean naloxone plasma concentration AP003 dosing periods. (time frame: PK samples taken at various timepoints over the course of Pre-dose and post-dose for 12 hours.). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05377255, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.