- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03802227
A Study Using fMRI Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users.
July 6, 2021 updated by: Nektar Therapeutics
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
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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).
Study Type
Interventional
Enrollment (Actual)
8
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Virginia
-
Richmond, Virginia, United States, 23298
- Investigator Site - Richmond
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1
NKTR-181 400 mg and oxycodone IR placebo
|
A combination of NKTR-181 and oxycodone IR placebo
|
Experimental: Group 2
Oxycodone IR 40 mg and NKTR-181 placebo
|
A combination of oxycodone IR and NKTR-181 placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brain Activity Measured Via fMRI
Time Frame: 8 hour period following dose of NKTR-181
|
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).
|
8 hour period following dose of NKTR-181
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Pupil Diameter Via Pupillometry
Time Frame: 24 hour period following dose administration Day 1 to 2
|
Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.
|
24 hour period following dose administration Day 1 to 2
|
Plasma Drug Concentration
Time Frame: 24 hour period following dose administration Day 1 to 2
|
Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.
|
24 hour period following dose administration Day 1 to 2
|
Time to Maximum Concentration (Tmax)
Time Frame: 24 hour period following dose administration Day 1 to 2
|
The amount of time needed for maximum drug concentration to be reached.
|
24 hour period following dose administration Day 1 to 2
|
Treatment-Emergent Adverse Events (TEAEs)
Time Frame: 19 days
|
Number of patients who experienced any type of adverse event as a result of one of the treatments.
|
19 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 22, 2018
Primary Completion (Actual)
December 17, 2019
Study Completion (Actual)
January 3, 2020
Study Registration Dates
First Submitted
November 15, 2018
First Submitted That Met QC Criteria
January 10, 2019
First Posted (Actual)
January 14, 2019
Study Record Updates
Last Update Posted (Actual)
July 8, 2021
Last Update Submitted That Met QC Criteria
July 6, 2021
Last Verified
July 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18-181-26
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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