Trial Outcomes & Findings for Pharmacodynamic Evaluation of Intramuscular Nalmefene Autoinjector 1.5 mg Compared to Intranasal Narcan 4 mg (NCT NCT06719986)
NCT ID: NCT06719986
Last Updated: 2025-07-03
Results Overview
To assess the change in minute ventilation at 5 minutes of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
5 minutes after opioid antagonist administration
Results posted on
2025-07-03
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.
The Qualification Phase (Part 1) was conducted prior to the Treatment Phase (Part 2) to identify subjects eligible for participation in Part 2. N=13 subjects who had not previously qualified in a similar study at the same site and N=11 subjects who had previously qualified in a similar study at the same site for a total of N=24 subjects who participated in the Treatment Phase (Part 2).
Participant milestones
| Measure |
Fentanyl Infusion
The Qualification Phase (Part 1) was conducted prior to Part 2 to identify subjects who had not previously qualified in a similar study at the same site. During Qualification, subjects were given an IV infusion of fentanyl titrated to produce up to an average of 50% decrease in minute ventilation.
|
Sequence 1 (Test-Reference-Test-Reference)
Treatment Phase (Part 2) - Sequence 1 - BABA.
This was a 4-period, 2-treatment, 2-sequence, replicate randomization.
Subjects received a single dose of Nalmefene Hydrochloride injection 1.5 mg for IM administration (Treatment B \[Test\]) on Day 1 in Period 1, then a single dose of Naloxone 4 mg for IN administration (Treatment A \[Reference\] on Day 1 in Period 2, then a single dose of Nalmefene Hydrochloride injection 1.5 mg for IM administration (Treatment B \[Test\]) on Day 1 in Period 3, then a single dose of Naloxone 4 mg for IN administration (Treatment A \[Reference\] on Day 1 in Period 4.
All completed subjects received two rounds of Nalmefene and 2 rounds of Naloxone.
|
Sequence 2 (Reference-Test-Reference-Test)
Treatment Phase (Part 2) - Sequence 2 - ABAB.
This was a 4-period, 2-treatment, 2-sequence, replicate randomization.
Subjects received a single dose of Naloxone 4 mg for IN administration (Treatment A \[Reference\]) on Day 1 in Period 1, then a single dose of Nalmefene Hydrochloride injection 1.5 mg for IM administration (Treatment B \[Test\]) on Day 1 in Period 2, then a single dose of Naloxone 4 mg for IN administration (Treatment A \[Reference\]) on Day 1 in Period 3, then a single dose of Nalmefene Hydrochloride injection 1.5 mg for IM administration (Treatment B \[Test\]) on Day 1 in Period 4.
All completed subjects received two rounds of Naloxone and 2 rounds of Nalmefene.
|
|---|---|---|---|
|
Part 1 Qualification (1 Day)
STARTED
|
13
|
0
|
0
|
|
Part 1 Qualification (1 Day)
COMPLETED
|
13
|
0
|
0
|
|
Part 1 Qualification (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
|
Qualification Washout (12 Hours)
STARTED
|
13
|
0
|
0
|
|
Qualification Washout (12 Hours)
COMPLETED
|
13
|
0
|
0
|
|
Qualification Washout (12 Hours)
NOT COMPLETED
|
0
|
0
|
0
|
|
Part 2 Period 1 (1 Day)
STARTED
|
0
|
12
|
12
|
|
Part 2 Period 1 (1 Day)
COMPLETED
|
0
|
12
|
12
|
|
Part 2 Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
|
Washout (up to 72 Hours)
STARTED
|
0
|
12
|
11
|
|
Washout (up to 72 Hours)
COMPLETED
|
0
|
11
|
11
|
|
Washout (up to 72 Hours)
NOT COMPLETED
|
0
|
1
|
0
|
|
Part 2 Period 2 (1 Day)
STARTED
|
0
|
12
|
11
|
|
Part 2 Period 2 (1 Day)
COMPLETED
|
0
|
12
|
11
|
|
Part 2 Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
|
Part 2 Period 3 (1 Day)
STARTED
|
0
|
12
|
11
|
|
Part 2 Period 3 (1 Day)
COMPLETED
|
0
|
12
|
11
|
|
Part 2 Period 3 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
|
Part 2 Period 4 (1 Day)
STARTED
|
0
|
11
|
11
|
|
Part 2 Period 4 (1 Day)
COMPLETED
|
0
|
11
|
11
|
|
Part 2 Period 4 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Fentanyl Infusion
The Qualification Phase (Part 1) was conducted prior to Part 2 to identify subjects who had not previously qualified in a similar study at the same site. During Qualification, subjects were given an IV infusion of fentanyl titrated to produce up to an average of 50% decrease in minute ventilation.
|
Sequence 1 (Test-Reference-Test-Reference)
Treatment Phase (Part 2) - Sequence 1 - BABA.
This was a 4-period, 2-treatment, 2-sequence, replicate randomization.
Subjects received a single dose of Nalmefene Hydrochloride injection 1.5 mg for IM administration (Treatment B \[Test\]) on Day 1 in Period 1, then a single dose of Naloxone 4 mg for IN administration (Treatment A \[Reference\] on Day 1 in Period 2, then a single dose of Nalmefene Hydrochloride injection 1.5 mg for IM administration (Treatment B \[Test\]) on Day 1 in Period 3, then a single dose of Naloxone 4 mg for IN administration (Treatment A \[Reference\] on Day 1 in Period 4.
All completed subjects received two rounds of Nalmefene and 2 rounds of Naloxone.
|
Sequence 2 (Reference-Test-Reference-Test)
Treatment Phase (Part 2) - Sequence 2 - ABAB.
This was a 4-period, 2-treatment, 2-sequence, replicate randomization.
Subjects received a single dose of Naloxone 4 mg for IN administration (Treatment A \[Reference\]) on Day 1 in Period 1, then a single dose of Nalmefene Hydrochloride injection 1.5 mg for IM administration (Treatment B \[Test\]) on Day 1 in Period 2, then a single dose of Naloxone 4 mg for IN administration (Treatment A \[Reference\]) on Day 1 in Period 3, then a single dose of Nalmefene Hydrochloride injection 1.5 mg for IM administration (Treatment B \[Test\]) on Day 1 in Period 4.
All completed subjects received two rounds of Naloxone and 2 rounds of Nalmefene.
|
|---|---|---|---|
|
Washout (up to 72 Hours)
Adverse Event
|
0
|
0
|
1
|
|
Washout (up to 72 Hours)
Withdrawal by Subject
|
0
|
1
|
0
|
Baseline Characteristics
Pharmacodynamic Evaluation of Intramuscular Nalmefene Autoinjector 1.5 mg Compared to Intranasal Narcan 4 mg
Baseline characteristics by cohort
| Measure |
All Study Participants
n=24 Participants
Subjects received Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration or Naloxone 4 mg for intranasal (IN) administration in a crossover fashion according to the randomization sequence.
|
|---|---|
|
Age, Continuous
|
39.1 years
STANDARD_DEVIATION 7.60 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 5 minutes after opioid antagonist administrationPopulation: Eligible analysis set was defined as subjects/periods who were randomized, received study drug, had at least 1 valid pharmacodynamic (PD) measurement, and their opioid-induced respiratory depressions (OIRDs) were worse than baseline for minute ventilation (MV) and transcutaneous CO2 (TCO2). The data for the overall treatment period was calculated as the average of available data from individual periods.
To assess the change in minute ventilation at 5 minutes of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Change in Minute Ventilation 5 Minutes From Opioid Induced Nadir
|
4.42 L/min
Standard Deviation 2.033
|
2.03 L/min
Standard Deviation 0.992
|
SECONDARY outcome
Timeframe: Baseline, 2.5, 5, 10, 15, 20, 30, and 90 minutes after opioid antagonist administrationPopulation: Eligible analysis set was defined as subjects/periods who were randomized, received study drug, had at least 1 valid pharmacodynamic (PD) measurement, and their opioid-induced respiratory depressions (OIRDs) were worse than baseline for minute ventilation (MV) and transcutaneous CO2 (TCO2). The data for overall treatment period was calculated as the average of available data from individual periods.
To assess the time course of changes in minute ventilation of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
Baseline
|
2.92 L/min
Standard Deviation 1.254
|
3.02 L/min
Standard Deviation 1.022
|
|
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
2.5 minutes
|
2.00 L/min
Standard Deviation 1.284
|
1.67 L/min
Standard Deviation 1.046
|
|
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
5 minutes
|
4.42 L/min
Standard Deviation 2.033
|
2.03 L/min
Standard Deviation 0.992
|
|
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
10 minutes
|
3.97 L/min
Standard Deviation 1.755
|
2.57 L/min
Standard Deviation 1.364
|
|
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
15 minutes
|
4.15 L/min
Standard Deviation 1.990
|
2.79 L/min
Standard Deviation 1.328
|
|
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
20 minutes
|
4.00 L/min
Standard Deviation 2.176
|
3.11 L/min
Standard Deviation 1.160
|
|
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
30 minutes
|
3.62 L/min
Standard Deviation 1.820
|
2.92 L/min
Standard Deviation 1.357
|
|
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir
90 minutes
|
2.74 L/min
Standard Deviation 1.519
|
2.55 L/min
Standard Deviation 0.994
|
SECONDARY outcome
Timeframe: up to 24 hours post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Maximum plasma concentration of nalmefene and naloxone.
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
8.3576 ng/mL
Standard Deviation 3.71139
|
5.6015 ng/mL
Standard Deviation 2.30753
|
SECONDARY outcome
Timeframe: 2.5 minutes post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Area under the plasma concentration-time curve from time zero to 2.5 minutes
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Area Under the Curve (AUC0-2.5)
|
0.0440 ng*hr/mL
Standard Deviation 0.03923
|
0.256 ng*hr/mL
Standard Deviation 0.03663
|
SECONDARY outcome
Timeframe: 5 minutes post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Area under the plasma concentration-time curve from time zero to 5 minutes
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Area Under the Curve (AUC0-5)
|
0.2225 ng*hr/mL
Standard Deviation 0.13565
|
0.1002 ng*hr/mL
Standard Deviation 0.11542
|
SECONDARY outcome
Timeframe: 10 minutes post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Area under the plasma concentration-time curve from time zero to 10 minutes
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Area Under the Curve (AUC0-10)
|
0.7576 ng*hr/mL
Standard Deviation 0.38147
|
0.3311 ng*hr/mL
Standard Deviation 0.27201
|
SECONDARY outcome
Timeframe: 15 minutes post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Area under the plasma concentration-time curve from time zero to 15 minutes
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Area Under the Curve (AUC0-15)
|
1.2716 ng*hr/mL
Standard Deviation 0.52366
|
0.6300 ng*hr/mL
Standard Deviation 0.43256
|
SECONDARY outcome
Timeframe: 20 minutes post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Area under the plasma concentration-time curve from time zero to 20 minutes
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Area Under the Curve (AUC0-20)
|
1.7479 ng*hr/mL
Standard Deviation 0.61346
|
0.9817 ng*hr/mL
Standard Deviation 0.61050
|
SECONDARY outcome
Timeframe: up to 24 hours post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Area under the plasma concentration-time curve from time zero to the time of last measurable concentration.
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=23 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Area Under the Curve (AUCt)
|
23.1620 ng*hr/mL
Standard Deviation 3.60968
|
13.4803 ng*hr/mL
Standard Deviation 2.78735
|
SECONDARY outcome
Timeframe: up to 24 hours post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Area under the plasma concentration-time curve from time zero to infinity.
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=22 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Area Under the Curve (AUCinf)
|
25.7412 ng*hr/mL
Standard Deviation 4.65028
|
13.4938 ng*hr/mL
Standard Deviation 2.87023
|
SECONDARY outcome
Timeframe: up to 24 hours post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Time to maximum plasma concentration of nalmefene and naloxone.
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax)
|
0.2083 hour
Interval 0.062 to 1.017
|
0.6667 hour
Interval 0.167 to 1.0
|
SECONDARY outcome
Timeframe: up to 24 hours post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Time to first measurable plasma concentration of nalmefene and naloxone.
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Time to First Measurable Plasma Concentration (Tlag)
|
0.0527 hour
Standard Deviation 0.01912
|
0.0464 hour
Standard Deviation 0.01023
|
SECONDARY outcome
Timeframe: up to 24 hours post-dosePopulation: Full analysis population was defined as all subjects who were randomized, received study drug and had at least 1 valid pharmacodynamics (PD) measurement. Pharmacokinetic analyses and summaries were based on the full analysis population. For the overall analysis, the values were averaged within each subject first, then the descriptive statistics were calculated.
Half life of nalmefene and naloxone.
Outcome measures
| Measure |
Nalmefene Hydrochloride (HCl) Injection
n=23 Participants
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=22 Participants
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|
|
Half-life (T1/2)
|
7.9754 hour
Standard Deviation 2.16550
|
1.6353 hour
Standard Deviation .050257
|
Adverse Events
Fentanyl Infusion
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Nalmefene Hydrochloride (HCl) Injection
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
Narcan Intranasal
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Fentanyl Infusion
n=13 participants at risk
The Qualification Phase (Part 1) was conducted prior to Part 2 to identify subjects who had not previously qualified in a similar study at the same site. During Qualification, subjects were given an IV infusion of fentanyl titrated to produce up to an average of 50% decrease in minute ventilation.
|
Nalmefene Hydrochloride (HCl) Injection
n=23 participants at risk
Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
|
Narcan Intranasal
n=24 participants at risk
Naloxone 4 mg for intranasal (IN) administration
Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration
|
|---|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/13 • 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).
|
17.4%
4/23 • 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).
|
0.00%
0/24 • 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).
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/13 • 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).
|
17.4%
4/23 • 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).
|
0.00%
0/24 • 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).
|
|
Ear and labyrinth disorders
Ear discomfort
|
0.00%
0/13 • 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).
|
13.0%
3/23 • 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).
|
0.00%
0/24 • 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).
|
|
Gastrointestinal disorders
Nausea
|
7.7%
1/13 • 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).
|
26.1%
6/23 • 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).
|
20.8%
5/24 • 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).
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/13 • 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).
|
8.7%
2/23 • 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).
|
8.3%
2/24 • 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).
|
|
Gastrointestinal disorders
Vomitting
|
0.00%
0/13 • 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).
|
13.0%
3/23 • 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).
|
4.2%
1/24 • 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).
|
|
General disorders
Feeling hot
|
7.7%
1/13 • 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).
|
47.8%
11/23 • 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).
|
16.7%
4/24 • 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).
|
|
General disorders
Chills
|
0.00%
0/13 • 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).
|
26.1%
6/23 • 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).
|
0.00%
0/24 • 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).
|
|
General disorders
Feeling abnormal
|
0.00%
0/13 • 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).
|
13.0%
3/23 • 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).
|
0.00%
0/24 • 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).
|
|
General disorders
Feeling cold
|
0.00%
0/13 • 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).
|
8.7%
2/23 • 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).
|
4.2%
1/24 • 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).
|
|
General disorders
Injection site pain
|
0.00%
0/13 • 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).
|
8.7%
2/23 • 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).
|
0.00%
0/24 • 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).
|
|
Nervous system disorders
Headache
|
0.00%
0/13 • 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).
|
21.7%
5/23 • 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).
|
20.8%
5/24 • 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).
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/13 • 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).
|
4.3%
1/23 • 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).
|
29.2%
7/24 • 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).
|
|
Nervous system disorders
Allodynia
|
0.00%
0/13 • 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).
|
21.7%
5/23 • 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).
|
8.3%
2/24 • 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).
|
|
Nervous system disorders
Dizziness
|
15.4%
2/13 • 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).
|
17.4%
4/23 • 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).
|
4.2%
1/24 • 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).
|
|
Nervous system disorders
Burning sensation
|
0.00%
0/13 • 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).
|
13.0%
3/23 • 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).
|
0.00%
0/24 • 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).
|
|
Psychiatric disorders
Irritability
|
0.00%
0/13 • 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).
|
13.0%
3/23 • 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).
|
4.2%
1/24 • 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).
|
|
Psychiatric disorders
Agitation
|
0.00%
0/13 • 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).
|
8.7%
2/23 • 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).
|
0.00%
0/24 • 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).
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/13 • 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).
|
8.7%
2/23 • 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).
|
4.2%
1/24 • 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).
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
7.7%
1/13 • 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).
|
4.3%
1/23 • 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).
|
12.5%
3/24 • 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).
|
|
Vascular disorders
Hot flush
|
7.7%
1/13 • 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).
|
13.0%
3/23 • 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).
|
4.2%
1/24 • 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).
|
|
Nervous system disorders
Somnolence
|
7.7%
1/13 • 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).
|
0.00%
0/23 • 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).
|
4.2%
1/24 • 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).
|
|
Nervous system disorders
Tension headache
|
7.7%
1/13 • 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).
|
0.00%
0/23 • 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).
|
0.00%
0/24 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal pruritus
|
15.4%
2/13 • 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).
|
0.00%
0/23 • 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).
|
0.00%
0/24 • 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).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
23.1%
3/13 • 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).
|
0.00%
0/23 • 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).
|
0.00%
0/24 • 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).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60