CompletedNCT06719986Updated Jul 3, 2025Results posted

Pharmacodynamic Evaluation of Intramuscular Nalmefene Autoinjector 1.5 mg Compared to Intranasal Narcan 4 mg

A Phase 1 interventional study of Nalmefene HCl injection and Naloxone HCl intranasal in Opioid Overdose, sponsored by Purdue Pharma LP. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-07-03.

Sponsored by Purdue Pharma LP (part of Knoa Pharma) · Phase 1, Interventional, and Treatment

From the registry’s dates

Registered 2 years 1 month after the study started (first participant enrolled Oct 2022, registered Dec 2024).

Phase: Phase 1
Study type: Interventional
Enrollment: 24
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: All

Study summary

The purpose of this study is to determine the pharmacodynamics (change in minute ventilation) of nalmefene when given as an autoinjector intramuscularly (IM; into the thigh) compared to naloxone when given intranasally (IN; into the nose) to healthy subjects with prior opioid exposure under steady state fentanyl concentrations (opioid agonism).

Conditions studied

Opioid Overdose

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Opiate Overdose 70

In context

Opiate Overdose

70 studies on the registry are indexed under Opiate Overdose; 11 are open to participants now.

This study's enrollment of 24 is below the median of 184 across 48 interventional studies indexed under Opiate Overdose.

Browse Opiate Overdose studies →

Lead sponsor

Purdue Pharma LP is the lead sponsor of 58 studies on the registry; none are open to participants now.

First submitted before Purdue Pharma LP became part of Knoa Pharma.

Browse Purdue Pharma LP studies →All Knoa Pharma studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Eligibility criteria

Key Inclusion Criteria include:

Healthy and free of significant abnormal findings as determined by medical history, physical examination, clinical laboratory values, vital signs, and .
Body weight ranging from 50 to 100 kg (110-220 lbs) and (BMI) within the range [18-30] kg/m2 (inclusive).
Willing to be compliant with the protocol, capable of subjective evaluation, if applicable, able to read and understand questionnaires, if applicable.

Key Exclusion Criteria include:

Females who are pregnant or lactating.
Any significant illness during the 30 days preceding the initial dose in this study.
History or any current conditions that might interfere with drug absorption, distribution, metabolism or excretion.
Refusal to abstain from caffeine or xanthine containing beverages entirely during confinement.
Refusal to abstain from consumption of alcoholic beverages 48 hours prior to initial study drug administration and through the end-of-study visit.
Difficulty with venous access or unsuitable for or unwilling to undergo catheter insertion.

Other inclusion/exclusion criteria may apply.

Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 24 participants (actual)

Study arms

Experimental
Nalmefene Hydrochloride (HCl) injection
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Drug: Nalmefene HCl injection
Active comparator
Narcan intranasal
Naloxone 4 mg for intranasal (IN) administration
Drug: Naloxone HCl intranasal

Interventions

DrugNalmefene HCl injection
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
DrugNaloxone HCl intranasal
Naloxone 4 mg for intranasal (IN) administration
Also known as: Narcan

What researchers measure

Primary outcomes

Change in Minute Ventilation 5 Minutes From Opioid Induced Nadir
To assess the change in minute ventilation at 5 minutes of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.
Time frame: 5 minutes after opioid antagonist administration

Secondary outcomes

Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
To assess the time course of changes in minute ventilation of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.
Time frame: Baseline, 2.5, 5, 10, 15, 20, 30, and 90 minutes after opioid antagonist administration
Maximum Plasma Concentration (Cmax)
Maximum plasma concentration of nalmefene and naloxone.
Time frame: up to 24 hours post-dose
Area Under the Curve (AUC0-2.5)
Area under the plasma concentration-time curve from time zero to 2.5 minutes
Time frame: 2.5 minutes post-dose
Area Under the Curve (AUC0-5)
Area under the plasma concentration-time curve from time zero to 5 minutes
Time frame: 5 minutes post-dose
Area Under the Curve (AUC0-10)
Area under the plasma concentration-time curve from time zero to 10 minutes
Time frame: 10 minutes post-dose
Area Under the Curve (AUC0-15)
Area under the plasma concentration-time curve from time zero to 15 minutes
Time frame: 15 minutes post-dose
Area Under the Curve (AUC0-20)
Area under the plasma concentration-time curve from time zero to 20 minutes
Time frame: 20 minutes post-dose
Area Under the Curve (AUCt)
Area under the plasma concentration-time curve from time zero to the time of last measurable concentration.
Time frame: up to 24 hours post-dose
Area Under the Curve (AUCinf)
Area under the plasma concentration-time curve from time zero to infinity.
Time frame: up to 24 hours post-dose
Time to Maximum Plasma Concentration (Tmax)
Time to maximum plasma concentration of nalmefene and naloxone.
Time frame: up to 24 hours post-dose
Time to First Measurable Plasma Concentration (Tlag)
Time to first measurable plasma concentration of nalmefene and naloxone.
Time frame: up to 24 hours post-dose
Half-life (T1/2)
Half life of nalmefene and naloxone.
Time frame: up to 24 hours post-dose

Results

Posted Jul 3, 2025

Participant flow

The first subject was dosed 03-October-2022 and the last subject completed the study 23-December-2022. The study was conducted at 1 site in the US.

Part 1 Qualification (1 Day)

Participant flow — Part 1 Qualification (1 Day)
Milestone	Fentanyl Infusion	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	13	0	0
Completed	13	0	0
Not completed	0	0	0

Qualification Washout (12 Hours)

Participant flow — Qualification Washout (12 Hours)
Milestone	Fentanyl Infusion	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	13	0	0
Completed	13	0	0
Not completed	0	0	0

Part 2 Period 1 (1 Day)

Participant flow — Part 2 Period 1 (1 Day)
Milestone	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	12	12
Completed	12	12
Not completed	0	0

Washout (up to 72 Hours)

Participant flow — Washout (up to 72 Hours)
Milestone	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	12	12
Completed	12	11
Not completed	0	1
Withdrew: Adverse event	0	1

Part 2 Period 2 (1 Day)

Participant flow — Part 2 Period 2 (1 Day)
Milestone	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	12	11
Completed	12	11
Not completed	0	0

Washout (up to 72 Hours)

Participant flow — Washout (up to 72 Hours)
Milestone	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	12	11
Completed	12	11
Not completed	0	0

Part 2 Period 3 (1 Day)

Participant flow — Part 2 Period 3 (1 Day)
Milestone	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	12	11
Completed	12	11
Not completed	0	0

Washout (up to 72 Hours)

Participant flow — Washout (up to 72 Hours)
Milestone	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	12	11
Completed	11	11
Not completed	1	0
Withdrew: Withdrawal by subject	1	0

Part 2 Period 4 (1 Day)

Participant flow — Part 2 Period 4 (1 Day)
Milestone	Sequence 1 (Test-Reference-Test-Reference)	Sequence 2 (Reference-Test-Reference-Test)
Started	11	11
Completed	11	11
Not completed	0	0

Outcome measures

PrimaryChange in Minute Ventilation 5 Minutes From Opioid Induced Nadir

To assess the change in minute ventilation at 5 minutes of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.

Time frame:: 5 minutes after opioid antagonist administration
Reported as:: Mean · L/min

Change in Minute Ventilation 5 Minutes From Opioid Induced Nadir
L/min	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Change in Minute Ventilation 5 Minutes From Opioid Induced Nadir	4.42 ± 2.033	2.03 ± 0.992

SecondaryChange in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir

To assess the time course of changes in minute ventilation of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.

Time frame:: Baseline, 2.5, 5, 10, 15, 20, 30, and 90 minutes after opioid antagonist administration
Reported as:: Mean · L/min

Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
L/min	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Baseline	2.92 ± 1.254	3.02 ± 1.022
2.5 minutes	2.00 ± 1.284	1.67 ± 1.046
5 minutes	4.42 ± 2.033	2.03 ± 0.992
10 minutes	3.97 ± 1.755	2.57 ± 1.364
15 minutes	4.15 ± 1.990	2.79 ± 1.328
20 minutes	4.00 ± 2.176	3.11 ± 1.160
30 minutes	3.62 ± 1.820	2.92 ± 1.357
90 minutes	2.74 ± 1.519	2.55 ± 0.994

SecondaryMaximum Plasma Concentration (Cmax)

Maximum plasma concentration of nalmefene and naloxone.

Time frame:: up to 24 hours post-dose
Reported as:: Mean · ng/mL

Maximum Plasma Concentration (Cmax)
ng/mL	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Maximum Plasma Concentration (Cmax)	8.3576 ± 3.71139	5.6015 ± 2.30753

SecondaryArea Under the Curve (AUC0-2.5)

Area under the plasma concentration-time curve from time zero to 2.5 minutes

Time frame:: 2.5 minutes post-dose
Reported as:: Mean · ng*hr/mL

Area Under the Curve (AUC0-2.5)
ng*hr/mL	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Area Under the Curve (AUC0-2.5)	0.0440 ± 0.03923	0.256 ± 0.03663

SecondaryArea Under the Curve (AUC0-5)

Area under the plasma concentration-time curve from time zero to 5 minutes

Time frame:: 5 minutes post-dose
Reported as:: Mean · ng*hr/mL

Area Under the Curve (AUC0-5)
ng*hr/mL	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Area Under the Curve (AUC0-5)	0.2225 ± 0.13565	0.1002 ± 0.11542

SecondaryArea Under the Curve (AUC0-10)

Area under the plasma concentration-time curve from time zero to 10 minutes

Time frame:: 10 minutes post-dose
Reported as:: Mean · ng*hr/mL

Area Under the Curve (AUC0-10)
ng*hr/mL	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Area Under the Curve (AUC0-10)	0.7576 ± 0.38147	0.3311 ± 0.27201

SecondaryArea Under the Curve (AUC0-15)

Area under the plasma concentration-time curve from time zero to 15 minutes

Time frame:: 15 minutes post-dose
Reported as:: Mean · ng*hr/mL

Area Under the Curve (AUC0-15)
ng*hr/mL	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Area Under the Curve (AUC0-15)	1.2716 ± 0.52366	0.6300 ± 0.43256

SecondaryArea Under the Curve (AUC0-20)

Area under the plasma concentration-time curve from time zero to 20 minutes

Time frame:: 20 minutes post-dose
Reported as:: Mean · ng*hr/mL

Area Under the Curve (AUC0-20)
ng*hr/mL	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Area Under the Curve (AUC0-20)	1.7479 ± 0.61346	0.9817 ± 0.61050

SecondaryArea Under the Curve (AUCt)

Area under the plasma concentration-time curve from time zero to the time of last measurable concentration.

Time frame:: up to 24 hours post-dose
Reported as:: Mean · ng*hr/mL

Area Under the Curve (AUCt)
ng*hr/mL	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Area Under the Curve (AUCt)	23.1620 ± 3.60968	13.4803 ± 2.78735

SecondaryArea Under the Curve (AUCinf)

Area under the plasma concentration-time curve from time zero to infinity.

Time frame:: up to 24 hours post-dose
Reported as:: Mean · ng*hr/mL

Area Under the Curve (AUCinf)
ng*hr/mL	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Area Under the Curve (AUCinf)	25.7412 ± 4.65028	13.4938 ± 2.87023

SecondaryTime to Maximum Plasma Concentration (Tmax)

Time to maximum plasma concentration of nalmefene and naloxone.

Time frame:: up to 24 hours post-dose
Reported as:: Median · hour

Time to Maximum Plasma Concentration (Tmax)
hour	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Time to Maximum Plasma Concentration (Tmax)	0.2083 (0.062 to 1.017)	0.6667 (0.167 to 1.000)

SecondaryTime to First Measurable Plasma Concentration (Tlag)

Time to first measurable plasma concentration of nalmefene and naloxone.

Time frame:: up to 24 hours post-dose
Reported as:: Mean · hour

Time to First Measurable Plasma Concentration (Tlag)
hour	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Time to First Measurable Plasma Concentration (Tlag)	0.0527 ± 0.01912	0.0464 ± 0.01023

SecondaryHalf-life (T1/2)

Half life of nalmefene and naloxone.

Time frame:: up to 24 hours post-dose
Reported as:: Mean · hour

Half-life (T1/2)
hour	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Half-life (T1/2)	7.9754 ± 2.16550	1.6353 ± .050257

Adverse events

Collected over All serious adverse events and adverse events were collected from the signing of the informed consent for study participation through 30 days after the subject's last dose of study drug or within 30 days after the last study visit or follow-up phone call (up to approximately 78 days).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Fentanyl Infusion	0/13 (0%)	0/13 (0%)	9/13 (69.2%)
Nalmefene Hydrochloride (HCl) Injection	0/23 (0%)	0/23 (0%)	20/23 (87%)
Narcan Intranasal	0/24 (0%)	0/24 (0%)	18/24 (75%)

Most frequent other events

Showing 10 of 25

Most frequent other events
Event	Fentanyl Infusion	Nalmefene Hydrochloride (HCl) Injection	Narcan Intranasal
Feeling hotGeneral disorders	1/13	11/23	4/24
DysgeusiaNervous system disorders	0/13	1/23	7/24
NauseaGastrointestinal disorders	1/13	6/23	5/24
ChillsGeneral disorders	0/13	6/23	0/24
PruritusSkin and subcutaneous tissue disorders	3/13	0/23	0/24
HeadacheNervous system disorders	0/13	5/23	5/24
AllodyniaNervous system disorders	0/13	5/23	2/24
PalpitationsCardiac disorders	0/13	4/23	0/24
TinnitusEar and labyrinth disorders	0/13	4/23	0/24
DizzinessNervous system disorders	2/13	4/23	1/24

Baseline characteristics

Age, Continuous
Age, Continuous(years)	All Study Participants
Mean	39.1 ± 7.60

Sex: Female, Male
Sex: Female, Male(Participants)	All Study Participants
Female	2
Male	22

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	All Study Participants
Hispanic or Latino	5
Not Hispanic or Latino	19
Unknown or Not Reported	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	All Study Participants
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	11
White	10
More than one race	3
Unknown or Not Reported	0

Study locations

1 site

Ohio Clinical Trials
Columbus, Ohio 43212, United States

References and documents

Study documents

Study protocol ↗ · Oct 12, 2022
Statistical analysis plan ↗ · Aug 7, 2022

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Oct 2022 to primary completion in Dec 2022, 2 months.

Results were first posted in Jul 2025, 2 years 6 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Dec 2, 2024
First posted: Dec 6, 2024
StartActual: Oct 3, 2022
Primary completionActual: Dec 23, 2022
CompletionActual: Dec 23, 2022
Results first posted: Jul 3, 2025
Last update: Jul 3, 2025

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Jul 3, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT06719986
Lead sponsor: Purdue Pharma LP
Responsible party: Sponsor
First posted: Dec 6, 2024
Start date: Oct 3, 2022
Primary completion: Dec 23, 2022
Completion: Dec 23, 2022
Results posted: Jul 3, 2025
Last update: Jul 3, 2025

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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