Clinical trial NCT03827629: A Study to Compare Bioavailability of Naloxone Nasal Spray and Naloxone Hydrochloride (HCl) Intramuscular Injection (IM) in Healthy Volunteers
Official title: A Phase 1, Open-Label, Randomized, Crossover, Comparative Bioavailability Study of Naloxone Nasal Spray and Naloxone Hydrochloride Intramuscular Injection in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: INSYS Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2019-02-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main objective of this study is to compare early exposures of two test formulations of Naloxone Nasal Spray with the reference formulation of Naloxone HCl IM Injection under fasted conditions.


Eligibility criteria: Inclusion Criteria:

* A minimum body weight of 50 kg and a body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m2)
* A seated blood pressure between 90 and 140 millimeters of mercury (mmHg) systolic/50 and 90 mmHg diastolic (inclusive)
* 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. Alcohol abuse was defined as greater than 14 drinks per week.
* Positive serology test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at 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 congestion.

Primary outcomes:
measure: Plasma Concentration of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 1 hour post-dose
measure: Partial Area Under the Concentration Curve (AUC) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 1 hour post-dose
Secondary outcomes:
measure: Area Under the Curve from Time 0 to the Last Measured Concentration (AUC0-t) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Area Under the Curve from Time 0 to Infinity (AUC0-inf) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Percentage of AUC0-inf Obtained by Extrapolation (AUCextrap) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Last Quantifiable Concentration (Clast) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Time of the Last Quantifiable Concentration (Tlast) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Time Prior to the First Measurable (Non-Zero) Concentration (Tlag) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Elimination Rate Constant (λz) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Elimination Half-Life (t1/2) of Unconjugated Naloxone
timeFrame: Pre-dose and at multiple time points up to 24 hours post-dose
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 10
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
affiliation: INSYS Therapeutics Inc
name: Giovanni DeCastro
role: STUDY_DIRECTOR
References: