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

NCT03802227 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 18-181-26
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Moderate to Severe Chronic Pain

Outcome Measures

Primary Outcomes (1)

• 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).

  8 hour period following dose of NKTR-181

Secondary Outcomes (4)

• Change in Pupil Diameter Via Pupillometry

  24 hour period following dose administration Day 1 to 2

• Plasma Drug Concentration

  24 hour period following dose administration Day 1 to 2

• Time to Maximum Concentration (Tmax)

  24 hour period following dose administration Day 1 to 2

• Treatment-Emergent Adverse Events (TEAEs)

  19 days

Study Arms (2)

Group 1

EXPERIMENTAL

NKTR-181 400 mg and oxycodone IR placebo

Drug: NKTR-181

Group 2

EXPERIMENTAL

Oxycodone IR 40 mg and NKTR-181 placebo

Drug: Oxycodone IR

Interventions

NKTR-181 DRUG

A combination of NKTR-181 and oxycodone IR placebo

Group 1

Oxycodone IR DRUG

A combination of oxycodone IR and NKTR-181 placebo

Group 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nektar Therapeutics: lead

Study Sites (1)

Investigator Site - Richmond

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Interventions

NKTR-181

Limitations and Caveats

The study was originally planned for 24 patients. However enrollment was stopped due to the CDP being stopped at 8 and therefore limits the generalizability of this data.

Results Point of Contact

• Title: Study Director
• Organization: Nektar Therapeutics

medicalaffairs@nektar.com

415-482-5416

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: January 14, 2019
• Study Start: October 22, 2018
• Primary Completion: December 17, 2019
• Study Completion: January 3, 2020
• Last Updated: July 8, 2021
• Results First Posted: May 27, 2021

Record last verified: 2021-07

Locations

US (1)