A Study Using Functional Magnetic Resonance Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users.

• ClinicalTrials.gov Identifier: NCT03802227
• Recruitment Status: Terminated
• First Posted: January 14, 2019
• Last Update Posted: February 18, 2020
• Sponsor: Nektar Therapeutics
• Information provided by (Responsible Party): Nektar Therapeutics

Tracking Information

• First Submitted Date: November 15, 2018
• First Posted Date: January 14, 2019
• Last Update Posted Date: February 18, 2020
• Actual Study Start Date: October 22, 2018
• Actual Primary Completion Date: December 17, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 10, 2019): Functional MRI BOLD signal in brain following NKTR-181 administration [ Time Frame: 8 hour period following dose administration Day 1 to 2 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 10, 2019)

• Change in pupil diameter via pupillometry [ Time Frame: Day 1 to 19 ]
• PK parameters [ex: maximum plasma drug concentration (Cmax)] [ Time Frame: 24 hour period following dose administration Day 1 to 2 ]
• PK parameters [ex: time to maximum concentration (Tmax)] [ Time Frame: 24 hour period following dose administration Day 1 to 2 ]
• Number of subjects with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 to 19 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Using Functional Magnetic Resonance 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 Functional Magnetic Resonance Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users
• 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).
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

A double-blind, double-dummy, parallel-group, randomized, positive control study.

Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science

• Condition: Moderate to Severe Chronic Pain

Intervention

• Drug: NKTR-181
  A combination of NKTR-181 and oxycodone IR placebo
• Drug: Oxycodone IR
  A combination of oxycodone IR and NKTR-181 placebo

Study Arms

• Experimental: Group 1
  NKTR-181 400 mg and oxycodone IR placebo
  Intervention: Drug: NKTR-181
• Experimental: Group 2
  Oxycodone IR 40 mg and NKTR-181 placebo
  Intervention: Drug: Oxycodone IR

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 14, 2020): 8
• Original Estimated Enrollment (submitted: January 10, 2019): 24
• Actual Study Completion Date: January 3, 2020
• Actual Primary Completion Date: December 17, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03802227
• Other Study ID Numbers: 18-181-26
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Nektar Therapeutics
• Study Sponsor: Nektar Therapeutics
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Nektar Therapeutics
• Verification Date: February 2020