HealthyPhase 1NCT06306391
Pharmacokinetics of Intravenous and Intranasal Formulations of Naloxone in Healthy Volunteers.
A Phase 1 study testing Intravenous naloxone and Intranasal naloxone in people with Healthy, run by Parc de Salut Mar at 2 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Intravenous naloxone and Intranasal naloxone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 2 sitesSpain
- Study dates
- 5 Mar 2024to 2 Sep 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- - 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
Show all 21Show fewer
- - 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.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital del Mar Research Institute
Barcelona, 08003
IMIM (Hospital del Mar Medical Research Institute)
Barcelona, 08003
About this study
Official title: 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.
Read the detailed description
Naloxone is a semisynthetic morphine derivative and is a specific opioid antagonist that acts competitively at opioid receptors. It reveals very high affinity for the opioid receptor sites. Naloxone does not possess the "agonistic" or morphine-like properties characteristic of other opioid antagonists. In the absence of opioids or agonistic effects of other opioid antagonists, it exhibits essentially no pharmacologic activity. Naloxone has not been shown to produce tolerance or cause physical or mental dependence. Intranasally administered naloxone has been demonstrated to be rapidly absorbed, as evidenced by very early appearance (as early as 1 minute after administration) of the active substance in systemic circulation. A study investigating intranasal naloxone (Nyxoid™) at doses of 1, 2, 4 mg (MR903-1501) shows that the median (range) tmax associated with intranasal administration of naloxone was 15 (10, 60) minutes for 1 mg, 30 (8, 60) minutes for 2 mg and 15 (10, 60) minutes for 4 mg intranasal doses. Onset of action following intranasal administration can reasonably be expected to occur in each individual before the tmax is reached.
The half value duration (HVD) for intranasal administration were longer than for intramuscular administration (intranasal, 2 mg, 1.27h, intramuscular, 0.4 mg, 1.09h) from which we can infer a longer duration of action of naloxone given by the intranasal rather than the intramuscular route. The overall aim is to develop a physiologically based pharmacokinetic (PBPK) model for drug release, disposition and dissolution following intranasal drug delivery. Following delivery, drug release from the formulations and disposition in the nasal cavity will be described. The model will also account for drug transport through epithelial tissue and mucociliary clearance. Predicted local brain and systemic PK will therefore be linked to drug release, dissolution, and disposition in the brain and the rest of the body. In vitro permeability, transporter kinetic and proteomics data from the olfactory region, as well as published clinical data following intravenous and intranasal delivery will be used to support this. Integration of all these processes in a dynamic model will help to disentangle different kinetic process which contribute to this complex system, which will help us to explore the interplay between various processes. Intranasal: 1.8 mg nasal spray, solution in single-dose container. Intravenous: 1 mg in total (from 0.4 mg/mL injectable solution) Doses selected, in the low range of those tested previously in clinical opioid overdose situations, were already tested experimentally in a bioavailability study in healthy subjects comparing the two routes of administration of naloxone that will be evaluated in the protocol.
- Conditions
- Healthy
- Being tested
- Intravenous naloxone, Intranasal naloxone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous naloxoneDrug
Also called Intravenous - washout - intranasal
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 naloxoneDrug
Also called Intranasal - washout - intravenous
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Intranasal naloxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of Naloxone on Heart Rate (HR).
To assess the effects of naloxone on HR; only results at 6 hours will be reported.
Measured: 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.
Measured: 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.
Measured: Up to 6 hours
Cmax
The mean maximum observed concentration (of intranasal and intravenous naloxone), calculated from individual plasma PK concentrations
Measured: 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.
Measured: 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.
Measured: up to 24 hours
Secondary outcomes (1)
Adverse Effects (AE)
AE was performed including number and percentage.
Measured: Up to 24 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start5 Mar 2024
- Primary completion13 May 2024
- Study completion2 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06306391
- Sponsor's protocol ID
- IMIMFCTL/NLX_1
- Status last verified
- May 2024
- First submitted
- 5 Mar 2024
- Last updated
- 6 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiologically Based Pharmacokinetic Modelling of Intravenous and Intranasal Formulations of Naloxone in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT06306391
- Acronym / sponsor ID
- IMIMFCTL/NLX_1
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 5 Mar 2024 (actual)
- Primary completion
- 13 May 2024 (actual)
- Study completion
- 2 Sep 2024 (actual)
- First posted
- 12 Mar 2024 (actual)
- Results
- Posted 6 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Naloxone is a semisynthetic morphine derivative and is a specific opioid antagonist that acts competitively at opioid receptors. It reveals very high affinity for the opioid receptor sites. Naloxone does not possess the "agonistic" or morphine-like properties characteristic of other opioid antagonists. In the absence of opioids or agonistic effects of other opioid antagonists, it exhibits essentially no pharmacologic activity. Naloxone has not been shown to produce tolerance or cause physical or mental dependence. Intranasally administered naloxone has been demonstrated to be rapidly absorbed, as evidenced by very early appearance (as early as 1 minute after administration) of the active substance in systemic circulation. A study investigating intranasal naloxone (Nyxoid™) at doses of 1, 2, 4 mg (MR903-1501) shows that the median (range) tmax associated with intranasal administration of naloxone was 15 (10, 60) minutes for 1 mg, 30 (8, 60) minutes for 2 mg and 15 (10, 60) minutes for 4 mg intranasal doses. Onset of action following intranasal administration can reasonably be expected to occur in each individual before the tmax is reached.
The half value duration (HVD) for intranasal administration were longer than for intramuscular administration (intranasal, 2 mg, 1.27h, intramuscular, 0.4 mg, 1.09h) from which we can infer a longer duration of action of naloxone given by the intranasal rather than the intramuscular route. The overall aim is to develop a physiologically based pharmacokinetic (PBPK) model for drug release, disposition and dissolution following intranasal drug delivery. Following delivery, drug release from the formulations and disposition in the nasal cavity will be described. The model will also account for drug transport through epithelial tissue and mucociliary clearance. Predicted local brain and systemic PK will therefore be linked to drug release, dissolution, and disposition in the brain and the rest of the body. In vitro permeability, transporter kinetic and proteomics data from the olfactory region, as well as published clinical data following intravenous and intranasal delivery will be used to support this. Integration of all these processes in a dynamic model will help to disentangle different kinetic process which contribute to this complex system, which will help us to explore the interplay between various processes. Intranasal: 1.8 mg nasal spray, solution in single-dose container. Intravenous: 1 mg in total (from 0.4 mg/mL injectable solution) Doses selected, in the low range of those tested previously in clinical opioid overdose situations, were already tested experimentally in a bioavailability study in healthy subjects comparing the two routes of administration of naloxone that will be evaluated in the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous naloxone | Experimental | Drug: Intravenous naloxoneAssignment 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. |
| Intranasal naloxone | Experimental | Drug: Intranasal naloxoneAssignment 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (21 listed)
- - 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous naloxoneAlso: Intravenous - washout - intranasalNyoxid 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). | Drug | Intravenous naloxone |
| Intranasal naloxoneAlso: Intranasal - washout - intravenousNaloxone 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). | Drug | Intranasal naloxone |
Primary outcome
Effects of Naloxone on Heart Rate (HR).
Time frame: Up to 6 hours.
To assess the effects of naloxone on HR; only results at 6 hours will be reported.
Effects of Naloxone on Systolic Blood Pressure (SBP).
Time frame: Up to 6 hours.
To assess the effects of naloxone on SBP; only results at 6 hours will be reported.
Effects of Naloxone on Diastolic Blood Pressure (DBP).
Time frame: Up to 6 hours
To assess the effects of naloxone on DBP; only results at 6 hours will be reported.
Cmax
Time frame: Blood samples were taken pre-dose and up to 24 hours after start of each Dose
The mean maximum observed concentration (of intranasal and intravenous naloxone), calculated from individual plasma PK concentrations
Tmax
Time frame: Blood samples were taken pre-dose and up to 24 hours after start of each Dose
Time of maximum observed concentration (of intranasal and intravenous naloxone), calculated from individual plasma PK concentrations.
AUC(0-24h)
Time frame: up to 24 hours
Area under the curve from 0 time to the last measurable concentration (of intravenous and intranasal naloxone), calculated from individual plasma PK concentrations.
1 secondary outcome
Adverse Effects (AE)
Time frame: Up to 24 hours.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intravenous naloxone and Intranasal naloxone in people with Healthy, run by Parc de Salut Mar at 2 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of Naloxone on Heart Rate (HR). (time frame: Up to 6 hours.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.