Pharmacodynamic Evaluation of Intranasal Nalmefene | NCT04828005

NCT04828005

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Intranasal Nalmefene	Experimental	Nalmefene hydrochloride nasal spray, 3mg, 1 spray	Drug: Nalmefene hydrochloride
Intranasal Naloxone	Active Comparator	Naloxone hydrochloride nasal spray, 4mg, 1 spray	Drug: Naloxone hydrochloride

Name	Type	Description	Arm Group Labels	Other Names
Nalmefene hydrochloride	Drug	3mg Nasal spray	Intranasal Nalmefene

Outcomes Module

Measure	Description	Time Frame
Change in Minute Ventilation	Change in minute ventilation from opioid induced nadir	5 minutes

Secondary Outcomes

Measure	Description	Time Frame
Maximum Change in Minute Ventilation	Maximum change in minute ventilation from opioid induced nadir	Up to 2 hours
Time to Maximum Change in Minute Ventilation	Time to maximum change in minute ventilation from opioid induced nadir

Eligibility Module

Name	Affiliation	Role
Shawn Searle, MD	PRA Health Sciences	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
PRA Health Sciences		Salt Lake City	Utah	84124	United States

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	Part 1 Setup (Ventilation Model): Remifentanil, Then Intranasal Naloxone	Subjects received First Treatment (1 Day), followed by Washout (4 Days), followed by Second Treatment (1 Day). Treatment in Part 1 Healthy volunteers with prior opioid exposure received pretreatment with ondansetron (8 mg, oral) and sodium citrate (30 mL, oral) 30 minutes to 1 hour prior to remifentanil infusion. Subjects started receiving a hypercapnic gas mixture (50% O2, 43% N2, 7% CO2) using a ventilatory response to hypercapnia (VRH) face mask at Time 0 minutes, followed by a remifentanil hydrochloride infusion at Time 5 minutes. Subjects received 4 mg IN naloxone hydrochloride at Time 25 minutes. Remifentanil infusion continued up to Time 115 minutes.
FG001	Part 1 Extension Setup (Ventilation Model): Remifentanil, Then Intranasal Naloxone	Subjects received First Treatment (1 Day) only. Treatment in Part 1 Extension. Healthy volunteers with prior opioid exposure received a naloxone challenge test on the day of clinical admission to ensure the subject was not physically dependent on opioids. Subjects then received pretreatment with famotidine (20 mg IV), ondansetron (8 mg, oral), and sodium citrate (30 mL, oral) 30 minutes to 1 hour prior to remifentanil infusion. Subjects started receiving a hypercapnic gas mixture (50% O2, 43% N2, 7% CO2) using a ventilatory response to hypercapnia (VRH) face mask at Time 0 minutes, followed by a remifentanil hydrochloride infusion at Time 10 minutes. IN naloxone hydrochloride was administered at Time 25 minutes. Remifentanil infusion continued up to Time 146 minutes.
FG002	Part 2: Intranasal Nalmefene Crossover to Intranasal Naloxone	Part 2 was a randomized, 2-treatment crossover study to compare Intranasal Nalmefene to Intranasal Naloxone. Subjects received First Treatment (1 Day), followed by Washout (4 Days), followed by Second Treatment (1 Day). Treatment in Part 2 Healthy volunteers with prior opioid exposure received a naloxone challenge test on the day of clinical admission to ensure the subject was not physically dependent on opioids. After the naloxone challenge test, eligibility review and completion of admission procedures, each subject was randomized to receive either IN nalmefene hydrochloride or IN naloxone hydrochloride in a 2-period crossover manner, with a 4-day washout period between doses. All subjects received pretreatment with famotidine (20 mg IV), ondansetron (8 mg, oral), and sodium citrate (30 mL, oral) 30 minutes to 1 hour prior to remifentanil infusion. All subjects started receiving a hypercapnic gas mixture (50% O2, 43% N2, 7% CO2) using a ventilatory response to hypercapnia (VRH) face mask at Time 0 minutes, followed by a remifentanil hydrochloride infusion at Time 10 minutes. In accordance with the randomization schedule, IN nalmefene hydrochloride (3 mg) or IN naloxone hydrochloride (4 mg) was administered at Time 25 minutes. Remifentanil infusion continued up to Time 146 minutes.
FG003	Part 2: Intranasal Naloxone Crossover to Intranasal Nalmefene	Part 2 was a randomized, 2-treatment crossover study to compare Intranasal Nalmefene to Intranasal Naloxone. Subjects received First Treatment (1 Day), followed by Washout (4 Days), followed by Second Treatment (1 Day). Treatment in Part 2 Healthy volunteers with prior opioid exposure received a naloxone challenge test on the day of clinical admission to ensure the subject was not physically dependent on opioids. After the naloxone challenge test, eligibility review and completion of admission procedures, each subject was randomized to receive either IN nalmefene hydrochloride or IN naloxone hydrochloride in a 2-period crossover manner, with a 4-day washout period between doses. All subjects received pretreatment with famotidine (20 mg IV), ondansetron (8 mg, oral), and sodium citrate (30 mL, oral) 30 minutes to 1 hour prior to remifentanil infusion. All subjects started receiving a hypercapnic gas mixture (50% O2, 43% N2, 7% CO2) using a ventilatory response to hypercapnia (VRH) face mask at Time 0 minutes, followed by a remifentanil hydrochloride infusion at Time 10 minutes. In accordance with the randomization schedule, IN nalmefene hydrochloride (3 mg) or IN naloxone hydrochloride (4 mg) was administered at Time 25 minutes. Remifentanil infusion continued up to Time 146 minutes.

Periods

Title

Milestones

Reasons Not Completed

Part 1 Setup: 1st Treatment (1 Day)

Type	Comment	Milestone Data
STARTED		FG0007 subjects FG0010 subjects FG0020 subjects FG0030 subjects
COMPLETED		FG0007 subjects FG0010 subjects FG0020 subjects FG0030 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Part 1 Setup: Washout (4 Days)

Type	Comment	Milestone Data
STARTED		FG0007 subjects FG0010 subjects FG0020 subjects FG003

Part 1 Setup: 2nd Treatment (1 Day)

Type	Comment	Milestone Data
STARTED		FG0005 subjects FG0010 subjects FG0020 subjects FG003

Part 1 Extension: 1st Treatment (1 Day)

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0018 subjectsIn the Part 1 Extension, there was no Washout or 2nd Treatment. FG0020 subjects FG003

Part 2: 1st Treatment (1 Day)

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG00234 subjects FG003

Part 2: Washout (4 Days)

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG00227 subjects FG003

Part 2: 2nd Treatment (1 Day)

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG00225 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part 1: Intranasal Nalmefene	Subjects received First Treatment (1 Day), followed by Washout (4 Days), followed by Second Treatment (1 Day). Treatment in Part 1 Healthy volunteers with prior opioid exposure received pretreatment with ondansetron (8 mg, oral) and sodium citrate (30 mL, oral) 30 minutes to 1 hour prior to remifentanil infusion. Subjects started receiving a hypercapnic gas mixture (50% O2, 43% N2, 7% CO2) using a ventilatory response to hypercapnia (VRH) face mask at Time 0 minutes, followed by a remifentanil hydrochloride infusion at Time 5 minutes. Subjects received 4 mg IN naloxone hydrochloride at Time 25 minutes. Remifentanil infusion continued up to Time 115 minutes.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Customized			Mean

Outcome Measures Module

Outcome Measures

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

Change in minute ventilation from opioid induced nadir

Posted

Mean

Standard Error

L/min

5 minutes

ID	Title	Description
OG000	Intranasal Naloxone	Naloxone hydrochloride nasal spray, 4mg, 1 spray Naloxone hydrochloride: 4mg Nasal Spray
OG001	Intranasal Nalmefene	Nalmefene hydrochloride nasal spray, 3mg, 1 spray Nalmefene hydrochloride: 3mg Nasal spray

Units	Counts

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Intranasal Nalmefene	Nalmefene hydrochloride nasal spray, 3mg, 1 spray Nalmefene hydrochloride: 3mg Nasal spray

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 7, 2021	May 19, 2023	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Apr 12, 2022	May 19, 2023	SAP_001.pdf

ID	Term
D009019	Morphinans
D053610	Opiate Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds