Back to resultsA Study Using fMRI Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users.
Primary Purpose
Moderate to Severe Chronic Pain
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NKTR-181
Oxycodone IR
Sponsored by
About this trial
This is an interventional basic science trial for Moderate to Severe Chronic Pain
Eligibility Criteria
Key Inclusion Criteria:
- Healthy male and female recreational opioid users, 18-65 years of age inclusive.
- Body Mass Index (BMI) between 19.0 to 45.0kg/m2
- Have at least one urine drug screen positive for opioids during Screening to confirm recreational opioid use. Subjects testing positive for methadone or buprenorphine prescribed for treatment will be excluded.
- Subjects must agree to practice adequate contraception as outlined in the protocol.
Key Exclusion Criteria:
- Any metal fragments or other bodily metal that would pose a risk to subjects during MRI scanning as determined by the MRI technologist and/or MRI physicist
- Any clinically significant disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, central nervous, or gastrointestinal systems or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of the study drug or would place the subject at increased risk
- History of clinically significant acute asthma or other obstructive airway disease requiring daily controller medication or any condition that may increase the risk for respiratory depression
- Current neurologic conditions such as convulsive disorders, or history of severe head injury.
- Any current DSM-5 axis I psychiatric disorder or neurological disorder requiring ongoing treatment
- Current substance use disorder (moderate to severe), other than Opioid, Nicotine, THC (tetrahydrocannabinol), cocaine, or caffeine as defined by DSM-5
- Physical dependence of opioids
- History of claustrophobia or any other psychiatric disorder that would preclude subject tolerance of MRI procedures.
- Current use of any medication that could affect central nervous system blood flow (e.g. certain cardiovascular medications, triptan migraine medications)
- Clinical Opiate Withdrawal Scale (COWS) score of greater than 5 during screening or prior to first scan.
- Positive urine drug screen for buprenorphine or methadone immediately prior to the first scan.
Sites / Locations
- Investigator Site - Richmond
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group 1
Group 2
Arm Description
NKTR-181 400 mg and oxycodone IR placebo
Oxycodone IR 40 mg and NKTR-181 placebo
Outcomes
Primary Outcome Measures
Brain Activity Measured Via fMRI
The primary objective of the study was to evaluate the effects of NKTR-181 on brain activity. Functional MRI assessments in subjects administered opioids such as morphine, buprenorphine, and nalbuphine have shown drug-induced signaling changes in reward structures such as the nucleus accumbens, orbitofrontal cortex, and hippocampus, as well as changes in the functional connectivity of reward circuitry (Becerra, 2006; Gear, 2013; Upadhyay, 2012).
Secondary Outcome Measures
Change in Pupil Diameter Via Pupillometry
Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.
Plasma Drug Concentration
Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.
Time to Maximum Concentration (Tmax)
The amount of time needed for maximum drug concentration to be reached.
Treatment-Emergent Adverse Events (TEAEs)
Number of patients who experienced any type of adverse event as a result of one of the treatments.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03802227
Brief Title
A Study Using fMRI Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users.
Official Title
A Phase 1 Double-Blind, Double-Dummy, Parallel-Group, Randomized, Positive Control Study Using fMRI to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Terminated
Why Stopped
Sponsor Decision
Study Start Date
October 22, 2018 (Actual)
Primary Completion Date
December 17, 2019 (Actual)
Study Completion Date
January 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nektar Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The main purpose of this study is to evaluate the effect of NKTR-181 on brain activity in healthy, non-physically dependent recreational opioid users. This study will last about 88 days for each participant.
Detailed Description
This study is a single-center study in which approximately 24 subjects will be randomized to one of two treatment groups. Subjects will enter a screening period between Day -28 and Day -2. Upon meeting all criteria for enrollment, on Day -1 subjects will enter the clinical research study unit (CRSU) for an overnight confinement. On Day 1, subjects will undergo a baseline MRI and will then be randomized to NKTR-181 or oxycodone immediate release (IR). Once randomized, subjects will receive a single dose of study drug (NKTR-181 or oxycodone IR) and matched alternate-treatment placebo. Subjects will undergo a series of three fMRIs (functional magnetic resonance imaging) post dose (at hours 1, 2, and 4). At post-dose hours 0.5, 1, 2, 3, 4, 5, 6, and 8, pupillometry will be performed and PK blood samples will be drawn. Following a 14- to 17-day safety follow-up period, subjects will return to the research facility clinic for the End of Study (EOS) visit (Day 16-19).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Moderate to Severe Chronic Pain
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
A double-blind, double-dummy, parallel-group, randomized, positive control study.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
NKTR-181 400 mg and oxycodone IR placebo
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Oxycodone IR 40 mg and NKTR-181 placebo
Intervention Type
Drug
Intervention Name(s)
NKTR-181
Intervention Description
A combination of NKTR-181 and oxycodone IR placebo
Intervention Type
Drug
Intervention Name(s)
Oxycodone IR
Intervention Description
A combination of oxycodone IR and NKTR-181 placebo
Primary Outcome Measure Information:
Title
Brain Activity Measured Via fMRI
Description
The primary objective of the study was to evaluate the effects of NKTR-181 on brain activity. Functional MRI assessments in subjects administered opioids such as morphine, buprenorphine, and nalbuphine have shown drug-induced signaling changes in reward structures such as the nucleus accumbens, orbitofrontal cortex, and hippocampus, as well as changes in the functional connectivity of reward circuitry (Becerra, 2006; Gear, 2013; Upadhyay, 2012).
Time Frame
8 hour period following dose of NKTR-181
Secondary Outcome Measure Information:
Title
Change in Pupil Diameter Via Pupillometry
Description
Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.
Time Frame
24 hour period following dose administration Day 1 to 2
Title
Plasma Drug Concentration
Description
Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.
Time Frame
24 hour period following dose administration Day 1 to 2
Title
Time to Maximum Concentration (Tmax)
Description
The amount of time needed for maximum drug concentration to be reached.
Time Frame
24 hour period following dose administration Day 1 to 2
Title
Treatment-Emergent Adverse Events (TEAEs)
Description
Number of patients who experienced any type of adverse event as a result of one of the treatments.
Time Frame
19 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria:
Healthy male and female recreational opioid users, 18-65 years of age inclusive.
Body Mass Index (BMI) between 19.0 to 45.0kg/m2
Have at least one urine drug screen positive for opioids during Screening to confirm recreational opioid use. Subjects testing positive for methadone or buprenorphine prescribed for treatment will be excluded.
Subjects must agree to practice adequate contraception as outlined in the protocol.
Key Exclusion Criteria:
Any metal fragments or other bodily metal that would pose a risk to subjects during MRI scanning as determined by the MRI technologist and/or MRI physicist
Any clinically significant disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, central nervous, or gastrointestinal systems or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of the study drug or would place the subject at increased risk
History of clinically significant acute asthma or other obstructive airway disease requiring daily controller medication or any condition that may increase the risk for respiratory depression
Current neurologic conditions such as convulsive disorders, or history of severe head injury.
Any current DSM-5 axis I psychiatric disorder or neurological disorder requiring ongoing treatment
Current substance use disorder (moderate to severe), other than Opioid, Nicotine, THC (tetrahydrocannabinol), cocaine, or caffeine as defined by DSM-5
Physical dependence of opioids
History of claustrophobia or any other psychiatric disorder that would preclude subject tolerance of MRI procedures.
Current use of any medication that could affect central nervous system blood flow (e.g. certain cardiovascular medications, triptan migraine medications)
Clinical Opiate Withdrawal Scale (COWS) score of greater than 5 during screening or prior to first scan.
Positive urine drug screen for buprenorphine or methadone immediately prior to the first scan.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Nektar Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Investigator Site - Richmond
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study Using fMRI Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users.
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