Pharmacokinetic Evaluation of a New Naloxone Nasal Swab, Naloxone Nasal Spray, and Intramuscular Naloxone Injection in Healthy Volunteers
Condition: Opioid Overdose
MeSH terms: Opiate Overdose
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): IM Naloxone Injection; Naloxone Nasal Spray; Naloxone Nasal Swab; Naloxone Nasal Swab; Naloxone Nasal Swab; Naloxone Nasal Swab
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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).; 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).; 4 mg naloxone nasal swab administered in nostril; 8 mg naloxone nasal swab administered in nostril; 12 mg naloxone nasal swab administered in nostril; 12.5 mg naloxone nasal swab administered in nostril
Intervention MeSH terms: Naloxone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment