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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06306391
• Other study ID #: IMIMFCTL/NLX_1
• Status: Recruiting
• Phase: Phase 1
• Start date: March 5, 2024
• Est. completion date: September 2024

Study information

• Verified date: March 2024
• Source: Parc de Salut Mar
• Contact: Ana Maria Aldea Perona, PhD
• Phone: (+34) 933160484
• Email: aaldea[@]researchmar.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

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).
• 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).

Locations

Country	Name	City	State
Spain	IMIM (Hospital del Mar Medical Research Institute)	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Parc de Salut Mar	Food and Drug Administration (FDA)

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse effects.		Up to 24 hours.
Primary	Effects of naloxone on heart rate (HR).		Up to 24 hours.
Primary	Effects of naloxone on systolic and diastolic blood pressure (BP).		Up to 24 hours.
Secondary	Effects of naloxone on plasma cortisol at visit 1 and visit 4.		Up to 24 hours.