Pharmacokinetic Evaluation of a New Naloxone Nasal Swab, Naloxone Nasal Spray, and Intramuscular Naloxone Injection in Healthy Volunteers

NCT05363501 | Completed Phase 1 FDA Drug

• 1 other identifier: PNC-20-001
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Opioid Overdose

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  13 days

Secondary Outcomes (4)

• Absorption Levels-Phase 1 and 2

  17 days

• Safety of Naloxone Swab- (Treatment emergent adverse events (TEAEs))-Phase 1 and 2

  17 days

• Absorption Levels-Phase 2

  13 days

• Dose Proportionality-Phase 2

  13 days

Study Arms (10)

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).

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).

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.

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.

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.

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.

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)

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)

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

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).

Drug: Naloxone Nasal Swab

Interventions

IM Naloxone Injection DRUG

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 IM Injection

Naloxone Nasal Spray DRUG

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).

Intranasal Naloxone Spray

Naloxone Nasal Swab DRUG

4 mg naloxone nasal swab administered in nostril

Single 4 mg naloxone nasal swab-Swirl method

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: For Phase 2, at least 20% of each gender are included in the trial.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Pocket Naloxone Corp: lead

Study Sites (1)

Altasciences

Québec, Quebec, Canada

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

• Sonnie Kim

  Pocket Naloxone Corp

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: May 6, 2022
• Study Start: January 21, 2021
• Primary Completion: April 3, 2022
• Study Completion: April 11, 2022
• Last Updated: May 6, 2022

Record last verified: 2021-12

Locations

CA (1)