Pharmacokinetics of Intravenous and Intranasal Formulations of Naloxone in Healthy Volunteers.

NCT06306391 | Completed Phase 1 Results

• 1 other identifier: IMIMFCTL/NLX_1
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase I interventional clinical trial and the aim will be to characterize the PK and PD of two formulations of naloxone (intranasal and intravenous) in healthy subjects, which will be used to verify/validate nasal-CNS-PBPK (Physiologically Based Pharmacokinetic) model predictions following intranasal dosing.

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• Effects of Naloxone on Heart Rate (HR).

  To assess the effects of naloxone on HR; only results at 6 hours will be reported.

  Up to 6 hours.

• Effects of Naloxone on Systolic Blood Pressure (SBP).

  To assess the effects of naloxone on SBP; only results at 6 hours will be reported.

  Up to 6 hours.

• Effects of Naloxone on Diastolic Blood Pressure (DBP).

  To assess the effects of naloxone on DBP; only results at 6 hours will be reported.

  Up to 6 hours

• Cmax

  The mean maximum observed concentration (of intranasal and intravenous naloxone), calculated from individual plasma PK concentrations

  Blood samples were taken pre-dose and up to 24 hours after start of each Dose

• Tmax

  Time of maximum observed concentration (of intranasal and intravenous naloxone), calculated from individual plasma PK concentrations.

  Blood samples were taken pre-dose and up to 24 hours after start of each Dose

• AUC(0-24h)

  Area under the curve from 0 time to the last measurable concentration (of intravenous and intranasal naloxone), calculated from individual plasma PK concentrations.

  up to 24 hours

Secondary Outcomes (1)

• Adverse Effects (AE)

  Up to 24 hours.

Study Arms (2)

Intravenous naloxone

EXPERIMENTAL

Assignment of treatment is sequence randomized. One single intravenous dose on Period 1 Day 1 and one single intranasal dose administered in supine position on Period 2 Day 1 or vice versa. Intravenous naloxone as IV bolus using external infusion pump will be administered to subjects after at least 8 hours (10 hours +/- 2 hours) of fasting conditions.

Drug: Intravenous naloxone

Intranasal naloxone

EXPERIMENTAL

Assignment of treatment is sequence randomized. One single intravenous dose on Period 1 Day 1 and one single intranasal dose administered in supine position on Period 2 Day 1 or vice versa. One intranasal dose of naloxone nasal spray will be administered in one nostril following the instructions described in the protocol after at least 8 hours (10 hours +/- 2 hours) of fasting conditions.

Drug: Intranasal naloxone

Interventions

Intravenous naloxone DRUG

Nyoxid 1.8 mg nasal spray, solution in single-dose container. Study drugs (naloxone nasal spray and naloxone intravenously) will be administered in 8 subjects in two sequences in fasting conditions (10 hours pre-dose and 4 hours post dose): Intranasal -\> washout period -\>intravenous (n=4) and Intravenous -\>washout period -\> intranasal (n=4).

Also known as: Intravenous - washout - intranasal

Intravenous naloxone

Intranasal naloxone DRUG

Naloxone Kern Pharma 1 mg in total (from 0.4 mg/mL injectable solution). Study drugs (naloxone nasal spray and naloxone intravenously) will be administered in 8 subjects in two sequences in fasting conditions (10 hours pre-dose and 4 hours post dose): Intranasal -\> washout period -\>intravenous (n=4) and Intravenous -\>washout period -\> intranasal (n=4).

Also known as: Intranasal - washout - intravenous

Intranasal naloxone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female volunteers according to physical examination, vital signs (blood pressure, heart rate and body temperature), ECG and safety laboratory parameters and results should be within normal ranges or considered as non-clinically relevant by the investigator.
• Age ≥ 18 and ≤ 55 years.
• Body mass index (BMI) ≥ 18 and ≤ 30.
• Able/willing to be compliant with the study restrictions.
• Able to read Spanish and adhere to study requirements.
• Signed informed consent prior to any study-mandated procedure.

You may not qualify if:

• \- Life-time substance use disorders (SUD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
• \- Consumption of prescribed opiates (in the last 6 months).
• \- Smoking.
• \- History of or ongoing clinically relevant diseases or conditions.
• \- Being under any administrative or legal supervision.
• \- Pregnancy and breastfeeding
• \- Positive blood or urine test for drugs of abuse or alcohol breath test prior to study drug administration.
• \- Life-time history of mental diseases.
• \- History of anxiety or depression not completely recovered within 12 months prior to study drug administration, as assessed by the Dual Diagnosis Screening Interview (DDSI).
• \- Any other clinically relevant disease or condition that in the judgment of the investigator might interfere with the subject's ability to comply with study procedures or requirements and/or bias the interpretation of the study results and/or jeopardize the subject's safety.
• \- Ongoing gastrointestinal diseases or history of gastrointestinal surgery affecting absorption.
• \- Subjects with a clinically significant disease within one month prior to study drug administration.
• \- Any clinically relevant findings in physical examination, vital signs, 12-lead ECG and safety laboratory parameters.
• \- Positive hepatitis or HIV test.
• \- Known hypersensitivity to any drug or drug excipients.

Sponsors & Collaborators

• Parc de Salut Mar: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (2)

Hospital del Mar Research Institute

Barcelona, 08003, Spain

Location

IMIM (Hospital del Mar Medical Research Institute)

Barcelona, 08003, Spain

Location

Results Point of Contact

• Title: Rafael de la Torre Fornell/Ana M aldea Perona
• Organization: Consorci PSMAR

rtorre2@researchmar.net

(+34) 93 3160484

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 12, 2024
• Study Start: March 5, 2024
• Primary Completion: May 13, 2024
• Study Completion: September 2, 2024
• Last Updated: May 6, 2026
• Results First Posted: May 6, 2026

Record last verified: 2024-05

Locations

ES (2)