A Study to Compare Bioavailability of Naloxone Nasal Spray, Naloxone Hydrochloride (HCl) Intravenous (IV) and Intramuscular Injection (IM) in Healthy Volunteers

A Phase 1, Open-Label, Randomized, Crossover, Comparative Bioavailability Study of Naloxone Nasal Spray and Naloxone Hydrochloride Intravenous and Intramuscular Injection in Healthy Volunteers

The main objective of this study was to compare the bioavailability of two test formulations of Naloxone Nasal Spray with the reference formulations of Naloxone HCl IV and IM injection under fasted conditions.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Treatment A: Naloxone Nasal Spray; Drug: Treatment B: Naloxone Nasal Spray; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A minimum body weight of 50 kg. Body mass index (BMI) between 18.0 and 32.0 kg/m2
• A seated blood pressure between 90 and 140 mmHg systolic/50 and 90 mmHg diastolic
• Female subjects had a negative serum β human chorionic gonadotropin (β-hCG) pregnancy test at screening

Exclusion Criteria:

• A known allergy or history of significant adverse reaction to naloxone, other opioids or related compounds, or to any of the excipients
• Any documented clinically significant infection, injury, or illness within 1 month prior to screening
• An active malignancy of any type, or had been diagnosed with cancer within 5 years prior to screening
• A documented history of alcohol or drug abuse/dependence/misuse or narcotic analgesic abuse/dependence/misuse within 2 years prior to screening
• A positive urine test result for alcohol, drugs, or cotinine at screening or check-in
• A condition that the investigator believed would have interfered with the ability to provide informed consent or comply with study instructions, or that could confound the interpretation of the study results or put the subject at undue risk
• Used any opioids for 30 days prior to Day 1
• Required treatment with monoamine oxidase inhibitors (MAOIs) within 30 days prior to Day 1 and during the study.
• Presence of an ongoing upper respiratory infection, rhinitis, rhinorrhea, or nasal congestions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1: Treatment Sequence A-D-C-B; Participants received Treatment A on Day 1 of Period 1, Treatment D on Day 1 of Period 2, Treatment C on Day 1 of Period 3 and Treatment B on Day 1 of Period 4.	Drug: Treatment A: Naloxone Nasal Spray; Participants received naloxone nasal spray following a 10 hour fast.; Drug: Treatment B: Naloxone Nasal Spray; Participants received naloxone nasal spray following a 10 hour fast.; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Participants received naloxone HCl IV injection following a 10 hour fast.; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection; Participants received naloxone HCl IM injection following a 10 hour fast.
EXPERIMENTAL: Cohort 2: Treatment Sequence B-C-D-A; Participants received Treatment B on Day 1 of Period 1, Treatment C on Day 1 of Period 2, Treatment D on Day 1 of Period 3 and Treatment A on Day 1 of Period 4.	Drug: Treatment A: Naloxone Nasal Spray; Participants received naloxone nasal spray following a 10 hour fast.; Drug: Treatment B: Naloxone Nasal Spray; Participants received naloxone nasal spray following a 10 hour fast.; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Participants received naloxone HCl IV injection following a 10 hour fast.; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection; Participants received naloxone HCl IM injection following a 10 hour fast.
EXPERIMENTAL: Cohort 3: Treatment Sequence C-A-B-D; Participants received Treatment C on Day 1 of Period 1, Treatment A on Day 1 of Period 2, Treatment B on Day 1 of Period 3 and Treatment D on Day 1 of Period 4.	Drug: Treatment A: Naloxone Nasal Spray; Participants received naloxone nasal spray following a 10 hour fast.; Drug: Treatment B: Naloxone Nasal Spray; Participants received naloxone nasal spray following a 10 hour fast.; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Participants received naloxone HCl IV injection following a 10 hour fast.; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection; Participants received naloxone HCl IM injection following a 10 hour fast.
EXPERIMENTAL: Cohort 4: Treatment Sequence D-B-A-C; Participants received Treatment D on Day 1 of Period 1, Treatment B on Day 1 of Period 2, Treatment A on Day 1 of Period 3 and Treatment C on Day 1 of Period 4.	Drug: Treatment A: Naloxone Nasal Spray; Participants received naloxone nasal spray following a 10 hour fast.; Drug: Treatment B: Naloxone Nasal Spray; Participants received naloxone nasal spray following a 10 hour fast.; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Participants received naloxone HCl IV injection following a 10 hour fast.; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection; Participants received naloxone HCl IM injection following a 10 hour fast.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve From Time 0 to the Last Measured Concentration (AUC0-t) for Unconjugated Naloxone	Pre-dose and at multiple time points up to 24 hours post-dose
AUC Extrapolated to Infinity (AUC0-inf) for Unconjugated Naloxone	Pre-dose and at multiple time points up to 24 hours post-dose
Maximum Plasma Concentration (Cmax) for Unconjugated Naloxone	Pre-dose and at multiple time points up to 24 hours post-dose
Time to Reach Maximum Plasma Concentration (Tmax) for Unconjugated Naloxone	Pre-dose and at multiple time points up to 24 hours post-dose
Time Prior to the First Measurable (Non-Zero) Concentration (Tlag) for Unconjugated Naloxone	Pre-dose and at multiple time points up to 24 hours post-dose
Elimination Rate Constant (λz) for Unconjugated Naloxone	Pre-dose and at multiple time points up to 24 hours post-dose
Elimination Half-Life (t1/2) of Unconjugated Naloxone	Pre-dose and at multiple time points up to 24 hours post-dose
Partial Area Under the Concentration Curve (AUC) of Unconjugated Naloxone	Pre-dose and at multiple time points up to 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Unconjugated Naloxone		Pre-dose and at multiple time points up to 2 hours post-dose
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A serious AE (SAE) is any AE that results in death, is life threatening, requires hospitalization or prolongs existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention.	Day 1 to Day 14

Collaborators and Investigators

• Sponsor: INSYS Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 23, 2018
• Primary Completion (ACTUAL): May 6, 2018
• Study Completion (ACTUAL): May 6, 2018

Study Registration Dates

• First Submitted: January 31, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (ACTUAL): February 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2019
• Last Update Submitted That Met QC Criteria: January 31, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: INS012-18-119

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No