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

NCT03827642 | Completed Phase 1 FDA Drug

• 1 other identifier: INS012-18-119
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (2)

• 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)

  Day 1 to Day 14

Study Arms (4)

Cohort 1: Treatment Sequence A-D-C-B

EXPERIMENTAL

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; Drug: Treatment B: Naloxone Nasal Spray; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection

Cohort 2: Treatment Sequence B-C-D-A

EXPERIMENTAL

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; Drug: Treatment B: Naloxone Nasal Spray; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection

Cohort 3: Treatment Sequence C-A-B-D

EXPERIMENTAL

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; Drug: Treatment B: Naloxone Nasal Spray; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection

Cohort 4: Treatment Sequence D-B-A-C

EXPERIMENTAL

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; Drug: Treatment B: Naloxone Nasal Spray; Drug: Treatment C: Naloxone HCl Intravenous (IV) Injection; Drug: Treatment D: Naloxone HCl Intramuscular (IM) Injection

Interventions

Treatment A: Naloxone Nasal Spray DRUG

Participants received naloxone nasal spray following a 10 hour fast.

Cohort 1: Treatment Sequence A-D-C-B; Cohort 2: Treatment Sequence B-C-D-A; Cohort 3: Treatment Sequence C-A-B-D; Cohort 4: Treatment Sequence D-B-A-C

Treatment B: Naloxone Nasal Spray DRUG

Participants received naloxone nasal spray following a 10 hour fast.

Cohort 1: Treatment Sequence A-D-C-B; Cohort 2: Treatment Sequence B-C-D-A; Cohort 3: Treatment Sequence C-A-B-D; Cohort 4: Treatment Sequence D-B-A-C

Treatment C: Naloxone HCl Intravenous (IV) Injection DRUG

Participants received naloxone HCl IV injection following a 10 hour fast.

Cohort 1: Treatment Sequence A-D-C-B; Cohort 2: Treatment Sequence B-C-D-A; Cohort 3: Treatment Sequence C-A-B-D; Cohort 4: Treatment Sequence D-B-A-C

Treatment D: Naloxone HCl Intramuscular (IM) Injection DRUG

Participants received naloxone HCl IM injection following a 10 hour fast.

Cohort 1: Treatment Sequence A-D-C-B; Cohort 2: Treatment Sequence B-C-D-A; Cohort 3: Treatment Sequence C-A-B-D; Cohort 4: Treatment Sequence D-B-A-C

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• INSYS Therapeutics Inc: lead

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Giovanni DeCastro

  INSYS Therapeutics Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 1, 2019
• Study Start: April 23, 2018
• Primary Completion: May 6, 2018
• Study Completion: May 6, 2018
• Last Updated: February 1, 2019

Record last verified: 2019-01

Locations

US (1)