Moderate to Severe Chronic PainPhase 1NCT03802227

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

A Phase 1 study testing NKTR-181 and Oxycodone IR in people with Moderate to Severe Chronic Pain, run by Nektar Therapeutics at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Moderate to Severe Chronic Pain
What is being tested?: NKTR-181 and Oxycodone IR
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteUnited States
Study dates: 22 Oct 2018to 3 Jan 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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

Show all 11Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Investigator Site - Richmond
Richmond, Virginia, 23298

Other trials in United States

About this study

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

Read the 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).

Conditions: Moderate to Severe Chronic Pain
Being tested: NKTR-181, Oxycodone IR

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03802227
Study group	Role	What they receive
Group 1	Experimental	NKTR-181 400 mg and oxycodone IR placebo Receives: Drug: NKTR-181
Group 2	Experimental	Oxycodone IR 40 mg and NKTR-181 placebo Receives: Drug: Oxycodone IR

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 8 hour period following dose of NKTR-181

Secondary outcomes (4)

Change in Pupil Diameter Via Pupillometry
Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.
Measured: 24 hour period following dose administration Day 1 to 2
Plasma Drug Concentration
Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.
Measured: 24 hour period following dose administration Day 1 to 2
Time to Maximum Concentration (Tmax)
The amount of time needed for maximum drug concentration to be reached.
Measured: 24 hour period following dose administration Day 1 to 2
Treatment-Emergent Adverse Events (TEAEs)
Number of patients who experienced any type of adverse event as a result of one of the treatments.
Measured: 19 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Oct 20183 Jan 2020

First posted14 Jan 2019
Study start22 Oct 2018
Primary completion17 Dec 2019
Study completion3 Jan 2020

Why it stopped: Sponsor Decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Moderate to Severe Chronic PainStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Model description: A double-blind, double-dummy, parallel-group, randomized, positive control study.
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03802227
Sponsor's protocol ID: 18-181-26
Status last verified: Jul 2021
First submitted: 15 Nov 2018
Last updated: 8 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 8 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03802227
Acronym / sponsor ID: 18-181-26
Conditions: Moderate to Severe Chronic Pain
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sponsor Decision
Enrolment: 8 participants (actual)
Lead sponsor: Nektar TherapeuticsIndustry (pharma, biotech, devices)
Study start: 22 Oct 2018 (actual)
Primary completion: 17 Dec 2019 (actual)
Study completion: 3 Jan 2020 (actual)
First posted: 14 Jan 2019 (actual)
Results: Posted 27 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2
Model description: A double-blind, double-dummy, parallel-group, randomized, positive control study.

Arm	Type	Receives
Group 1	Experimental	Drug: NKTR-181NKTR-181 400 mg and oxycodone IR placebo
Group 2	Experimental	Drug: Oxycodone IROxycodone IR 40 mg and NKTR-181 placebo

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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 (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NKTR-181A combination of NKTR-181 and oxycodone IR placebo	Drug	Group 1
Oxycodone IRA combination of oxycodone IR and NKTR-181 placebo	Drug	Group 2

Primary outcome

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).

4 secondary outcomes

Change in Pupil Diameter Via Pupillometry
Time frame: 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
Time to Maximum Concentration (Tmax)
Time frame: 24 hour period following dose administration Day 1 to 2
Treatment-Emergent Adverse Events (TEAEs)
Time frame: 19 days

Results and safety

Results posted to the registry on 27 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NKTR-181	4	4
Oxycodone IR 40 mg	4	4

Primary outcome: Brain Activity Measured Via fMRI

Time frame: 8 hour period following dose of NKTR-181. Mean (Standard Deviation). Unit: Correlation Coefficient

Measure	NKTR-181 n = 4	Oxycodone IR 40 mg n = 4
Effective Connectivity between ACC and R Hippocampus at Baseline	0.0 (0.12)	0.2 (0.34)
Effective Connectivity between ACC and R Hippocampus after 1 hour	0.0 (0.28)	0.0 (0.21)
Effective Connectivity between ACC and R Hippocampus after 2 hours	0.1 (0.20)	-0.1 (0.10)
Effective Connectivity between ACC and R Hippocampus after 4 hours	0.0 (0.20)	0.0 (0.48)
Effective Connectivity between ACC and R Hippocampus after 8 hours	-0.1 (0.02)	0.2 (0.07)
Effective Connectivity between R Amygdala and mPFC at Baseline	0.1 (0.38)	0.0 (0.14)
Effective Connectivity between R Amygdala and mPFC after 1 hour	-0.2 (0.41)	0.1 (0.34)
Effective Connectivity between R Amygdala and mPFC after 2 hours	0.2 (0.21)	0.4 (0.51)

Population analysed: Subjects who had sufficient MRI data for NKTR-181 or oxycodone IR treatment to allow for analysis of modulation of brain circuitry.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 19 days post-dose of NKTR-181 or Oxycodone IR 40 mg. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
NKTR-181	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Oxycodone IR 40 mg	0 of 4 (0%)	0 of 4 (0%)	0 of 4

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Study Director study director

Nektar Therapeutics

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NKTR-181 and Oxycodone IR in people with Moderate to Severe Chronic Pain, run by Nektar Therapeutics at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brain Activity Measured Via fMRI (time frame: 8 hour period following dose of NKTR-181). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03802227.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2021.