A Study Using fMRI 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
• Results First Posted: May 27, 2021
• Last Update Posted: July 8, 2021
• Sponsor: Nektar Therapeutics
• Information provided by (Responsible Party): Nektar Therapeutics

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.

Condition or disease	Intervention/treatment	Phase
Moderate to Severe Chronic Pain	Drug: NKTR-181; Drug: Oxycodone IR	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• 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
• 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
• Actual Study Start Date: October 22, 2018
• Actual Primary Completion Date: December 17, 2019
• Actual Study Completion Date: January 3, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; NKTR-181 400 mg and oxycodone IR placebo	Drug: NKTR-181; A combination of NKTR-181 and oxycodone IR placebo
Experimental: Group 2; Oxycodone IR 40 mg and NKTR-181 placebo	Drug: Oxycodone IR; A combination of oxycodone IR and NKTR-181 placebo

Outcome Measures

Primary Outcome Measures :

1. 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).

Secondary Outcome Measures :

1. 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.
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.
3. 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.
4. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Virginia

Investigator Site - Richmond

Richmond, Virginia, United States, 23298

Sponsors and Collaborators

Nektar Therapeutics

Investigators

• Study Director: Study Director; Nektar Therapeutics

  Study Documents (Full-Text)

Documents provided by Nektar Therapeutics:

Study Protocol  [PDF] October 24, 2019

Statistical Analysis Plan  [PDF] August 25, 2019

More Information

• Responsible Party: Nektar Therapeutics
• ClinicalTrials.gov Identifier: NCT03802227
• Other Study ID Numbers: 18-181-26
• First Posted: January 14, 2019
• Results First Posted: May 27, 2021
• Last Update Posted: July 8, 2021
• Last Verified: July 2021

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

Additional relevant MeSH terms:

Chronic Pain; Pain; Neurologic Manifestations; Oxycodone; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents