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

Physiologically Based Pharmacokinetic Modelling of Intravenous and Intranasal Formulations of Naloxone in Healthy Volunteers.

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Intravenous naloxone; Drug: Intranasal naloxone

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ana Maria Aldea Perona, PhD; Phone Number: (+34) 933160484; Email: aaldea@researchmar.net
• Study Contact Backup: Name: Rafael De la Torre Fornell, PhD; Phone Number: (+34) 933160484; Email: rtorre2@researchmar.net

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Recruiting
    • IMIM (Hospital del Mar Medical Research Institute)
    • Contact: Rafael De la Torre Fornell, PharmD, PhD; Phone Number: 1780 00343160780; Email: rtorre@imim.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Use of drugs known to induce or inhibit hepatic drug metabolism (e.g., cimetidine) within one month prior to study administration or during the study and use of citrus juice during the study.
• Any prescription or over-the-counter (OTC) product including herbal, homeopathic, vitamins, minerals and nutritional supplements within one week prior to study drug administration.
• Intake of foods or beverages containing xanthine (more than 5 units of coffee, tea or cola drinks per day).
• Donation of blood or plasma within one month prior to study drug administration or transfusion of blood or plasma for medical/surgical reasons or intention to donate blood or plasma within one month after study drug administration.
• History of inadequate venous access and/or experience of difficulty donating blood.
• Subject included in a clinical study within 3 months prior to study drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous naloxone	Drug: Intravenous naloxone; 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).
Experimental: Intranasal naloxone	Drug: Intranasal naloxone; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effects of naloxone on heart rate (HR).	Up to 24 hours.
Effects of naloxone on systolic and diastolic blood pressure (BP).	Up to 24 hours.

Secondary Outcome Measures

Outcome Measure	Time Frame
Effects of naloxone on plasma cortisol at visit 1 and visit 4.	Up to 24 hours.

Other Outcome Measures

Outcome Measure	Time Frame
Adverse effects.	Up to 24 hours.

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Collaborators: Food and Drug Administration (FDA)

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2024
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: March 5, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

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: IMIMFCTL/NLX_1

Drug and device information, study documents

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