Opioid OverdosePhase 1NCT05363501
Pharmacokinetic Evaluation of a New Naloxone Nasal Swab, Naloxone Nasal Spray, and Intramuscular Naloxone Injection in Healthy Volunteers
A Phase 1 study testing IM Naloxone Injection, Naloxone Nasal Spray and Naloxone Nasal Swab in people with Opioid Overdose, run by Pocket Naloxone Corp at 1 site in Canada.
Trial summary
The study consists of two Phases with the first phase (Pilot Phase) divided into two sub phases. In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to the first drug administration on Day -1 until approximately 12 hours following the last study drug administration. 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?
- IM Naloxone Injection, Naloxone Nasal Spray and Naloxone Nasal Swab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteCanada
- Study dates
- 21 Jan 2021to 11 Apr 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
- Provision of signed and dated informed consent form (ICF)
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Healthy adult male or female
- If female, meets 1 of the following criteria:
- Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include:
- Abstinence from heterosexual intercourse from the first study drug administration through to at least 30 days after the last dose of the study drug
Show all 15Show fewer
- 1 of the following highly-effective contraceptive methods, used from at least 28 days prior to the first study drug administration through to at least 30 days after the last dose of the study drug: Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch) Intrauterine device (with or without hormones) Male partner vasectomized at least 6 months prior to the first study drug administration
- The following effective contraceptive method, used from the first study drug administration through to at least 30 days after the last dose of the study drug:
- Male condom with diaphragm/cervical cap plus spermicide Or
- Male partner has had a vasectomy less than 6 months prior to dosing, and the female subject agrees to use an additional acceptable contraceptive method from the first study drug administration through to at least 30 days after the last dose of the study drug Or
- Is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a postmenopausal state (i.e. at least 1 year without menses without an alternative medical condition prior to the first study drug administration)
- Aged at least 18 years but not older than 55 years
- Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
- Non- or ex-smoker (An ex smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration)
- Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs), ECG, and/or nasal cavity examination, as determined by an investigator
Who cannot join
- Female who is lactating at screening
- Female who is pregnant according to the pregnancy test at screening or prior to the first study drug administration
- Seated blood pressure higher than 140/90 mmHg at screening or prior to the first study drug administration
- History of significant hypersensitivity to naloxone or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
- Presence or history of significant gastrointestinal, liver or kidney disease, or any other condition that is known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects
- History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
Show all 21Show fewer
- Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment
- Any intranasal conditions including nostril piercing, abnormal nasal anatomy, nasal symptoms (i.e., blocked and/or runny nose, nasal polyps, etc.), or having a product sprayed into the nasal cavity prior to drug administration
- Current or recent upper respiratory tract infection (within 28 days before the first study drug administration)
- Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
- Any clinically significant illness in the 28 days prior to the first study drug administration
- Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of an investigator would put into question the status of the participant as healthy
- Any history of tuberculosis
- Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration
- Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus antibody tests
- Any other clinically significant abnormalities at screening that would, in the opinion of an investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
- Inclusion in a previous group for this clinical study (for Phase 2 only)
- Intake of naloxone in the 28 days prior to the first study drug administration
- Intake of an Investigational Product (IP) in the 28 days prior to the first study drug administration
- Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration
- Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single Dose, Crossover, Pharmacokinetic Evaluation of a New Naloxone Nasal Swab, Naloxone Nasal Spray, and Intramuscular Naloxone Injection in Healthy Volunteers
The study consists of two Phases with the first phase (Pilot Phase) divided into two sub phases.
In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to the first drug administration on Day -1 until approximately 12 hours following the last study drug administration. Screening of alcohol and drugs of abuse will be performed before the first study drug administration. For female subjects, a pregnancy test will be performed before the first drug administration. Clinical nasal irritation rating and the Brief Smell Identification Test will be performed at screening.
Read the detailed description
The study consists of two Phases with the first phase (Pilot Phase) divided into two sub phases.
In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to the first drug administration on Day -1 until approximately 12 hours following the last study drug administration. Screening of alcohol and drugs of abuse will be performed before the first study drug administration. For female subjects, a pregnancy test will be performed before the first drug administration. Clinical nasal irritation rating and the Brief Smell Identification Test will be performed at screening.
Phases 1A and , 1B, and 1C (Pilot Phase) The first sub-phase, Phase 1A, will be an inpatient, 5-period, 5-treatment, crossover study involving 10 healthy subjects.
In Phase 1A of the study, qualified subjects will receive one of the following treatment in the morning, after a 10 hour overnight fast:
- Treatment-1: Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle).
- Treatment-2: Single 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use).
- Treatment-3: Single 8 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
- Treatment-4: Single 4 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
- Treatment-5: Single 12 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
Based on preliminary results from Phase 1A, additional administration technique and higher dose will be tested. The second sub-phase, Phase 1B, will be a separate inpatient crossover study involving 10 healthy subjects which will start after completion of Phase 1A. Every attempt will be made to include the same subjects from Phase 1A in Phase 1B.
In Phase 1B of the study, qualified subjects will receive one of the following treatments in the morning, after a 10 hour overnight fast:
- Treatment-1: Single 12 mg naloxone nasal swab administered into the nasal cavity - administered in one nostril and using two fingers to squeeze outside of both nostrils.
- Treatment-2: Two 12 mg naloxone nasal swabs in both nostrils- administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially)
- Treatment-3: Two 8 mg naloxone nasal swab in both nostrils - administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially) For all intranasal treatments (nasal spray and nasal swab), participants will be instructed to not breathe through the nose during treatment administration. The same nostril will be used throughout the study for all nasal treatments requiring one nostril only administration. If a Coronavirus Disease 2019 (COVID-19) test is performed prior to administration, the opposite nostril will be used for administration for treatments requiring one nostril administration.
The order in which subjects receive their treatment will not be randomized. During Phase 1A, subjects will receive Treatment-1 in period 1, Treatment-2 in period 2, Treatment-3 in period 3, Treatment-4 in period 4, and Treatment-5 in period 5. In Phase 1B, subjects will receive Treatment-1 in period 1, Treatment-2 in period 2, and Treatment-3 in period 3. There will be a 4 day wash out window between treatment periods. At the end of Phase 1A and Phase 1B, a dose will be selected as the proposed target dose for the Phase 2 to confirm the PK profiles.
Phase 2 (Confirmatory Phase)
Phase 2 of the study will be an inpatient, randomized, laboratory-blinded, balanced, 4-way (4 treatments) crossover study with 4 sequences (Williams design). Below are the 4 treatments to be utilized:
- Treatment-1: Single target naloxone nasal swab dose identified in Phase 1 (12.5 mg) administered as one swab in one nostril, using the insert into nostril and squeeze method of administration.
- Treatment-2: Single target naloxone nasal swab dose identified in Phase 1 (12.5 mg) using the insert into each nostril and squeeze method of administration (two doses given in total).
- Treatment-3: Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle).
- Treatment-4: Single 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use) For all intranasal treatments (nasal spray and nasal swab), participants will be instructed to not breathe through the nose during treatment administration. The same nostril will be used throughout the study for all nasal treatments except Treatment-2 where the swab administered in both nostrils. If a COVID-19 test is performed prior to administration, the opposite nostril will be used for administration of all single swab or spray doses.
- Conditions
- Opioid Overdose
- Being tested
- IM Naloxone Injection, Naloxone Nasal Spray, Naloxone Nasal Swab
- Medical subject headings
- Opiate Overdose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IM Naloxone InjectionDrug
Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle).
Naloxone Nasal SprayDrug
Single 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use).
Naloxone Nasal SwabDrug
4 mg naloxone nasal swab administered in nostril
Naloxone Nasal SwabDrug
8 mg naloxone nasal swab administered in nostril
Naloxone Nasal SwabDrug
12 mg naloxone nasal swab administered in nostril
Naloxone Nasal SwabDrug
12.5 mg naloxone nasal swab administered in nostril
| Study group | Role | What they receive |
|---|---|---|
| Naloxone IM Injection | Active comparator | Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle). Receives: Drug: IM Naloxone Injection |
| Intranasal Naloxone Spray | Active comparator | Single 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use). Receives: Drug: Naloxone Nasal Spray |
| Single 8 mg naloxone nasal swab-Swirl method | Experimental | Single 8 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa. Receives: Drug: Naloxone Nasal Swab |
| Single 4 mg naloxone nasal swab-Swirl method | Experimental | Single 4 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa. Receives: Drug: Naloxone Nasal Swab |
| Single 12 mg naloxone nasal swab-Swirl method | Experimental | Single 12 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa. Receives: Drug: Naloxone Nasal Swab |
| Single 12 mg naloxone nasal swab-Squeeze method | Experimental | Single 12 mg naloxone nasal swab administered into the nasal cavity - administered in one nostril and using two fingers to squeeze outside of both nostrils. Receives: Drug: Naloxone Nasal Swab |
| Single 12 mg naloxone nasal swab in each nostril-Squeeze method | Experimental | Two 12 mg naloxone nasal swabs in both nostrils- administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially) Receives: Drug: Naloxone Nasal Swab |
| Single 8 mg naloxone nasal swab in each nostril-Squeeze method | Experimental | Two 8 mg naloxone nasal swab in both nostrils - administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially) Receives: Drug: Naloxone Nasal Swab |
| Single 12.5 mg naloxone nasal swab-Squeeze method | Experimental | Single target naloxone nasal swab dose identified in Phase 1(12.5 mg) administered as one swab in one nostril, using the insert into nostril and squeeze method of administration Receives: Drug: Naloxone Nasal Swab |
| Single 12.5 mg naloxone nasal swab in each nostril-Squeeze method | Experimental | Single target naloxone nasal swab dose identified in Phase 1 (12.5 mg) using the insert into each nostril and squeeze method of administration (two doses given in total). Receives: Drug: Naloxone Nasal Swab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of Various Naloxone Administrations (Maximum plasma concentration (Cmax))-Phase 1
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Maximum plasma concentration (Cmax) will be measured.
Measured: 17 days
Pharmacokinetics of Various Naloxone Administrations (Area Under the Curve (AUC))-Phase 1
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Area Under the Curve (AUC)will be measured.
Measured: 17 days
Pharmacokinetics of Various Naloxone Administrations (Partial Area Under the Curve (AUC))-Phase 1
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Partial Area Under the Curve (AUC) will be measured.
Measured: 17 days
Dose Selection (Maximum plasma concentration (Cmax))-Phase 1
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects.
Maximum plasma concentration (Cmax) will be measured.
Measured: 17 days
Dose Selection (Area Under the Curve (AUC))-Phase 1
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects. Area Under the Curve (AUC) will be measured.
Measured: 17 days
Dose Selection (Partial Area Under the Curve (AUC))-Phase 1
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects. Partial Area Under the Curve (AUC) will be measured.
Measured: 17 days
Bioavailability (Maximum plasma concentration (Cmax))-Phase 2
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Maximum plasma concentration (Cmax) will be measured.
Measured: 13 days
Bioavailability (Area Under the Curve (AUC))-Phase 2
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Area Under the Curve (AUC) will be measured.
Measured: 13 days
Bioavailability (Partial Area Under the Curve (AUC))-Phase 2
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Partial Area Under the Curve (AUC) will be measured.
Measured: 13 days
Secondary outcomes (4)
Absorption Levels-Phase 1 and 2
To compare the absorption levels of intranasal naloxone swab at early time points post -delivery (within the first 15 minutes) with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects.
Measured: 17 days
Safety of Naloxone Swab- (Treatment emergent adverse events (TEAEs))-Phase 1 and 2
To determine the safety and tolerability of intranasal naloxone swab doses (4, 8, 12 and 12.5 mg), particularly with respect to nasal irritation (erythema, edema, and erosion) and olfactory nerve abnormalities in healthy subjects. will be included in the adverse event summaries.
Measured: 17 days
Absorption Levels-Phase 2
To compare the absorption levels of the nasal swab at early time points post-delivery (within the first 15 minutes) with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects.
Measured: 13 days
Dose Proportionality-Phase 2
To evaluate the dose proportionality of naloxone nasal swab target dose (12.5 mg).
Measured: 13 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2022
- Study start21 Jan 2021
- Primary completion3 Apr 2022
- Study completion11 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pocket Naloxone Corp
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sonnie Kim, Study director, Pocket Naloxone Corp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05363501
- Sponsor's protocol ID
- PNC-20-001
- Status last verified
- Dec 2021
- First submitted
- 4 Apr 2022
- Last updated
- 6 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Dose, Crossover, Pharmacokinetic Evaluation of a New Naloxone Nasal Swab, Naloxone Nasal Spray, and Intramuscular Naloxone Injection in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT05363501
- Acronym / sponsor ID
- PNC-20-001
- Conditions
- Opioid Overdose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Pocket Naloxone CorpIndustry (pharma, biotech, devices)
- Study start
- 21 Jan 2021 (actual)
- Primary completion
- 3 Apr 2022 (actual)
- Study completion
- 11 Apr 2022 (actual)
- First posted
- 6 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.
The study consists of two Phases with the first phase (Pilot Phase) divided into two sub phases.
In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to the first drug administration on Day -1 until approximately 12 hours following the last study drug administration. Screening of alcohol and drugs of abuse will be performed before the first study drug administration. For female subjects, a pregnancy test will be performed before the first drug administration. Clinical nasal irritation rating and the Brief Smell Identification Test will be performed at screening.
Detailed description
The study consists of two Phases with the first phase (Pilot Phase) divided into two sub phases.
In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to the first drug administration on Day -1 until approximately 12 hours following the last study drug administration. Screening of alcohol and drugs of abuse will be performed before the first study drug administration. For female subjects, a pregnancy test will be performed before the first drug administration. Clinical nasal irritation rating and the Brief Smell Identification Test will be performed at screening.
Phases 1A and , 1B, and 1C (Pilot Phase) The first sub-phase, Phase 1A, will be an inpatient, 5-period, 5-treatment, crossover study involving 10 healthy subjects.
In Phase 1A of the study, qualified subjects will receive one of the following treatment in the morning, after a 10 hour overnight fast:
- Treatment-1: Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle).
- Treatment-2: Single 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use).
- Treatment-3: Single 8 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
- Treatment-4: Single 4 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
- Treatment-5: Single 12 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
Based on preliminary results from Phase 1A, additional administration technique and higher dose will be tested. The second sub-phase, Phase 1B, will be a separate inpatient crossover study involving 10 healthy subjects which will start after completion of Phase 1A. Every attempt will be made to include the same subjects from Phase 1A in Phase 1B.
In Phase 1B of the study, qualified subjects will receive one of the following treatments in the morning, after a 10 hour overnight fast:
- Treatment-1: Single 12 mg naloxone nasal swab administered into the nasal cavity - administered in one nostril and using two fingers to squeeze outside of both nostrils.
- Treatment-2: Two 12 mg naloxone nasal swabs in both nostrils- administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially)
- Treatment-3: Two 8 mg naloxone nasal swab in both nostrils - administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially) For all intranasal treatments (nasal spray and nasal swab), participants will be instructed to not breathe through the nose during treatment administration. The same nostril will be used throughout the study for all nasal treatments requiring one nostril only administration. If a Coronavirus Disease 2019 (COVID-19) test is performed prior to administration, the opposite nostril will be used for administration for treatments requiring one nostril administration.
The order in which subjects receive their treatment will not be randomized. During Phase 1A, subjects will receive Treatment-1 in period 1, Treatment-2 in period 2, Treatment-3 in period 3, Treatment-4 in period 4, and Treatment-5 in period 5. In Phase 1B, subjects will receive Treatment-1 in period 1, Treatment-2 in period 2, and Treatment-3 in period 3. There will be a 4 day wash out window between treatment periods. At the end of Phase 1A and Phase 1B, a dose will be selected as the proposed target dose for the Phase 2 to confirm the PK profiles.
Phase 2 (Confirmatory Phase)
Phase 2 of the study will be an inpatient, randomized, laboratory-blinded, balanced, 4-way (4 treatments) crossover study with 4 sequences (Williams design). Below are the 4 treatments to be utilized:
- Treatment-1: Single target naloxone nasal swab dose identified in Phase 1 (12.5 mg) administered as one swab in one nostril, using the insert into nostril and squeeze method of administration.
- Treatment-2: Single target naloxone nasal swab dose identified in Phase 1 (12.5 mg) using the insert into each nostril and squeeze method of administration (two doses given in total).
- Treatment-3: Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle).
- Treatment-4: Single 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use) For all intranasal treatments (nasal spray and nasal swab), participants will be instructed to not breathe through the nose during treatment administration. The same nostril will be used throughout the study for all nasal treatments except Treatment-2 where the swab administered in both nostrils. If a COVID-19 test is performed prior to administration, the opposite nostril will be used for administration of all single swab or spray doses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Naloxone IM Injection | Active comparator | Drug: IM Naloxone InjectionSingle 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle). |
| Intranasal Naloxone Spray | Active comparator | Drug: Naloxone Nasal SpraySingle 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use). |
| Single 8 mg naloxone nasal swab-Swirl method | Experimental | Drug: Naloxone Nasal SwabSingle 8 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa. |
| Single 4 mg naloxone nasal swab-Swirl method | Experimental | Drug: Naloxone Nasal SwabSingle 4 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa. |
| Single 12 mg naloxone nasal swab-Swirl method | Experimental | Drug: Naloxone Nasal SwabSingle 12 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa. |
| Single 12 mg naloxone nasal swab-Squeeze method | Experimental | Drug: Naloxone Nasal SwabSingle 12 mg naloxone nasal swab administered into the nasal cavity - administered in one nostril and using two fingers to squeeze outside of both nostrils. |
| Single 12 mg naloxone nasal swab in each nostril-Squeeze method | Experimental | Drug: Naloxone Nasal SwabTwo 12 mg naloxone nasal swabs in both nostrils- administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially) |
| Single 8 mg naloxone nasal swab in each nostril-Squeeze method | Experimental | Drug: Naloxone Nasal SwabTwo 8 mg naloxone nasal swab in both nostrils - administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially) |
| Single 12.5 mg naloxone nasal swab-Squeeze method | Experimental | Drug: Naloxone Nasal SwabSingle target naloxone nasal swab dose identified in Phase 1(12.5 mg) administered as one swab in one nostril, using the insert into nostril and squeeze method of administration |
| Single 12.5 mg naloxone nasal swab in each nostril-Squeeze method | Experimental | Drug: Naloxone Nasal SwabSingle target naloxone nasal swab dose identified in Phase 1 (12.5 mg) using the insert into each nostril and squeeze method of administration (two doses given in total). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Provision of signed and dated informed consent form (ICF)
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Healthy adult male or female
- If female, meets 1 of the following criteria:
- Male condom with diaphragm/cervical cap plus spermicide Or
Key exclusion criteria (21 listed)
- Female who is lactating at screening
- Female who is pregnant according to the pregnancy test at screening or prior to the first study drug administration
- Seated blood pressure higher than 140/90 mmHg at screening or prior to the first study drug administration
- History of significant hypersensitivity to naloxone or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
- Presence or history of significant gastrointestinal, liver or kidney disease, or any other condition that is known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects
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 |
|---|---|---|
| IM Naloxone InjectionSingle 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle). | Drug | Naloxone IM Injection |
| Naloxone Nasal SpraySingle 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use). | Drug | Intranasal Naloxone Spray |
| Naloxone Nasal Swab4 mg naloxone nasal swab administered in nostril | Drug | Single 4 mg naloxone nasal swab-Swirl method |
| Naloxone Nasal Swab8 mg naloxone nasal swab administered in nostril | Drug | Single 8 mg naloxone nasal swab in each nostril-Squeeze method, Single 8 mg naloxone nasal swab-Swirl method |
| Naloxone Nasal Swab12 mg naloxone nasal swab administered in nostril | Drug | Single 12 mg naloxone nasal swab in each nostril-Squeeze method, Single 12 mg naloxone nasal swab-Squeeze method, Single 12 mg naloxone nasal swab-Swirl method |
| Naloxone Nasal Swab12.5 mg naloxone nasal swab administered in nostril | Drug | Single 12.5 mg naloxone nasal swab in each nostril-Squeeze method, Single 12.5 mg naloxone nasal swab-Squeeze method |
Primary outcome
Pharmacokinetics of Various Naloxone Administrations (Maximum plasma concentration (Cmax))-Phase 1
Time frame: 17 days
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Maximum plasma concentration (Cmax) will be measured.
Pharmacokinetics of Various Naloxone Administrations (Area Under the Curve (AUC))-Phase 1
Time frame: 17 days
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Area Under the Curve (AUC)will be measured.
Pharmacokinetics of Various Naloxone Administrations (Partial Area Under the Curve (AUC))-Phase 1
Time frame: 17 days
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Partial Area Under the Curve (AUC) will be measured.
Dose Selection (Maximum plasma concentration (Cmax))-Phase 1
Time frame: 17 days
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects. Maximum plasma concentration (Cmax) will be measured.
Dose Selection (Area Under the Curve (AUC))-Phase 1
Time frame: 17 days
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects. Area Under the Curve (AUC) will be measured.
Dose Selection (Partial Area Under the Curve (AUC))-Phase 1
Time frame: 17 days
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects. Partial Area Under the Curve (AUC) will be measured.
Bioavailability (Maximum plasma concentration (Cmax))-Phase 2
Time frame: 13 days
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Maximum plasma concentration (Cmax) will be measured.
Bioavailability (Area Under the Curve (AUC))-Phase 2
Time frame: 13 days
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Area Under the Curve (AUC) will be measured.
Bioavailability (Partial Area Under the Curve (AUC))-Phase 2
Time frame: 13 days
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Partial Area Under the Curve (AUC) will be measured.
4 secondary outcomes
Absorption Levels-Phase 1 and 2
Time frame: 17 days
Safety of Naloxone Swab- (Treatment emergent adverse events (TEAEs))-Phase 1 and 2
Time frame: 17 days
Absorption Levels-Phase 2
Time frame: 13 days
Dose Proportionality-Phase 2
Time frame: 13 days
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 6 May 2022.
Related trials for Opioid Overdose
Not yet recruitingObservational study
Disease Intervention Specialist (DIS) for SUD
Substance Use Disorder (SUD), Opioid Use Disorder
Not yet recruiting
Prevention and Rapid Outreach for Treatment, Engagement, and Care Transition From the Emergency Department
Opioid Overdose Prevention, HIV Prevention and Care
Not yet recruiting
Remote Intervention to Prevent Overdose
Accidental Overdose of Opiate
Enrolling by invitation
PATH to Reducing Burnout Among Peers Who Deliver Overdose Prevention Services (R33 Phase Clinical Trial)
Burnout, Secondary Trauma
Active, not recruiting
Improving Access to Naloxone to Prevent Opioid Overdose Deaths (SAIA-Naloxone)
Overdose, Implementation as Usual
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.
Sonnie Kim study director
Pocket Naloxone Corp
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 IM Naloxone Injection, Naloxone Nasal Spray and Naloxone Nasal Swab in people with Opioid Overdose, run by Pocket Naloxone Corp at 1 site in Canada.
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 15 inclusion and 21 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 6 May 2022. 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 Canada. 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?
Pharmacokinetics of Various Naloxone Administrations (Maximum plasma concentration (Cmax))-Phase 1 (time frame: 17 days). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2022.