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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nalmefene Hydrochloride (HCl) injection | Experimental | Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration |
|
| Narcan intranasal | Active Comparator | Naloxone 4 mg for intranasal (IN) administration |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nalmefene HCl injection | Drug | Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 5 minutes after opioid antagonist administration |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, 2.5, 5, 10, 15, 20, 30, and 90 minutes after opioid antagonist administration |
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Key Inclusion Criteria include:
Key Exclusion Criteria include:
Other inclusion/exclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ohio Clinical Trials | Columbus | Ohio | 43212 | United States |
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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).
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 Qualification (1 Day) |
| |||||||||||||
| Qualification Washout (12 Hours) |
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| Part 2 Period 1 (1 Day) |
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| Washout (up to 72 Hours) |
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| Part 2 Period 2 (1 Day) |
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| Washout (up to 72 Hours) |
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| Part 2 Period 3 (1 Day) |
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| Washout (up to 72 Hours) |
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| Part 2 Period 4 (1 Day) |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | L/min | 5 minutes after opioid antagonist administration |
|
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA version 25.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Leader | Purdue Pharma | 1-888-726-7535 | Purduemedinfo@pharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 12, 2022 | Mar 4, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 7, 2022 | Mar 4, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000083682 | Opiate Overdose |
| ID | Term |
|---|---|
| D062787 | Drug Overdose |
| D063487 | Prescription Drug Misuse |
| D000076064 | Drug Misuse |
| D019966 | Substance-Related Disorders |
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| ID | Term |
|---|---|
| C038981 | nalmefene |
| D009270 | Naloxone |
| ID | Term |
|---|---|
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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| Naloxone HCl intranasal | Drug | Naloxone 4 mg for intranasal (IN) administration |
|
|
| Maximum Plasma Concentration (Cmax) |
Maximum plasma concentration of nalmefene and naloxone. |
| 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 | 2.5 minutes post-dose |
| Area Under the Curve (AUC0-5) | Area under the plasma concentration-time curve from time zero to 5 minutes | 5 minutes post-dose |
| Area Under the Curve (AUC0-10) | Area under the plasma concentration-time curve from time zero to 10 minutes | 10 minutes post-dose |
| Area Under the Curve (AUC0-15) | Area under the plasma concentration-time curve from time zero to 15 minutes | 15 minutes post-dose |
| Area Under the Curve (AUC0-20) | Area under the plasma concentration-time curve from time zero to 20 minutes | 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. | up to 24 hours post-dose |
| Area Under the Curve (AUCinf) | Area under the plasma concentration-time curve from time zero to infinity. | up to 24 hours post-dose |
| Time to Maximum Plasma Concentration (Tmax) | Time to maximum plasma concentration of nalmefene and naloxone. | up to 24 hours post-dose |
| Time to First Measurable Plasma Concentration (Tlag) | Time to first measurable plasma concentration of nalmefene and naloxone. | up to 24 hours post-dose |
| Half-life (T1/2) | Half life of nalmefene and naloxone. | up to 24 hours post-dose |
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| NOT COMPLETED |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Narcan Intranasal | Naloxone 4 mg for intranasal (IN) administration Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration |
|
|
| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | L/min | Baseline, 2.5, 5, 10, 15, 20, 30, and 90 minutes after opioid antagonist administration |
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) | Maximum plasma concentration of nalmefene and naloxone. | 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. | Posted | Mean | Standard Deviation | ng/mL | up to 24 hours post-dose |
|
|
|
| Secondary | Area Under the Curve (AUC0-2.5) | Area under the plasma concentration-time curve from time zero to 2.5 minutes | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | 2.5 minutes post-dose |
|
|
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| Secondary | Area Under the Curve (AUC0-5) | Area under the plasma concentration-time curve from time zero to 5 minutes | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | 5 minutes post-dose |
|
|
|
| Secondary | Area Under the Curve (AUC0-10) | Area under the plasma concentration-time curve from time zero to 10 minutes | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | 10 minutes post-dose |
|
|
|
| Secondary | Area Under the Curve (AUC0-15) | Area under the plasma concentration-time curve from time zero to 15 minutes | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | 15 minutes post-dose |
|
|
|
| Secondary | Area Under the Curve (AUC0-20) | Area under the plasma concentration-time curve from time zero to 20 minutes | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | 20 minutes post-dose |
|
|
|
| Secondary | Area Under the Curve (AUCt) | Area under the plasma concentration-time curve from time zero to the time of last measurable concentration. | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | up to 24 hours post-dose |
|
|
|
| Secondary | Area Under the Curve (AUCinf) | Area under the plasma concentration-time curve from time zero to infinity. | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | up to 24 hours post-dose |
|
|
|
| Secondary | Time to Maximum Plasma Concentration (Tmax) | Time to maximum plasma concentration of nalmefene and naloxone. | 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. | Posted | Median | Full Range | hour | up to 24 hours post-dose |
|
|
|
| Secondary | Time to First Measurable Plasma Concentration (Tlag) | Time to first measurable plasma concentration of nalmefene and naloxone. | 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. | Posted | Mean | Standard Deviation | hour | up to 24 hours post-dose |
|
|
|
| Secondary | Half-life (T1/2) | Half life of nalmefene and naloxone. | 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. | Posted | Mean | Standard Deviation | hour | up to 24 hours post-dose |
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| 9 |
| 13 |
| EG001 | Nalmefene Hydrochloride (HCl) Injection | Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration Nalmefene HCl injection: Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration | 0 | 23 | 0 | 23 | 20 | 23 |
| EG002 | Narcan Intranasal | Naloxone 4 mg for intranasal (IN) administration Naloxone HCl intranasal: Naloxone 4 mg for intranasal (IN) administration | 0 | 24 | 0 | 24 | 18 | 24 |
| Tinnitus | Ear and labyrinth disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Vomitting | Gastrointestinal disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Feeling cold | General disorders | MedDRA version 25.1 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA version 25.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA version 25.1 | Systematic Assessment |
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| Allodynia | Nervous system disorders | MedDRA version 25.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA version 25.1 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA version 25.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA version 25.1 | Systematic Assessment |
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| Tension headache | Nervous system disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Nasal pruritus | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 25.1 | Systematic Assessment |
|
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| D064419 |
| Chemically-Induced Disorders |
| D009293 | Opioid-Related Disorders |
| D000079524 | Narcotic-Related Disorders |
| D001523 | Mental Disorders |
| D006572 |
| Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| 5 minutes |
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| 10 minutes |
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| 15 minutes |
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| 20 minutes |
|
| 30 minutes |
|
| 90 minutes |
|