Trial Outcomes & Findings for A Study Using fMRI Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users. (NCT NCT03802227)
NCT ID: NCT03802227
Last Updated: 2021-07-08
Results Overview
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).
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
8 participants
Primary outcome timeframe
8 hour period following dose of NKTR-181
Results posted on
2021-07-08
Participant Flow
Treatment assignments were based on a computer-generated randomization scheduled prepared by SynteractHCR Inc. prior to study start
Participant milestones
| Measure |
NKTR-181
Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR
|
Oxycodone IR 40 mg
Once capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study Using fMRI Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users.
Baseline characteristics by cohort
| Measure |
NKTR-181
n=4 Participants
Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR oxycodone IR
|
Oxycodone IR 40 mg
n=4 Participants
One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.5 years
STANDARD_DEVIATION 7.42 • n=5 Participants
|
43.5 years
STANDARD_DEVIATION 3.42 • n=7 Participants
|
41.0 years
STANDARD_DEVIATION 5.98 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Height (cm)
|
166.3 centimeters
STANDARD_DEVIATION 5.94 • n=5 Participants
|
182.0 centimeters
STANDARD_DEVIATION 2.44 • n=7 Participants
|
174.1 centimeters
STANDARD_DEVIATION 9.39 • n=5 Participants
|
|
Weight (kg)
|
81.5 kilograms
STANDARD_DEVIATION 21.30 • n=5 Participants
|
83.8 kilograms
STANDARD_DEVIATION 5.93 • n=7 Participants
|
82.7 kilograms
STANDARD_DEVIATION 14.52 • n=5 Participants
|
|
BMI (kg/m2)
|
29.7 kilograms per meter squared
STANDARD_DEVIATION 8.83 • n=5 Participants
|
25.3 kilograms per meter squared
STANDARD_DEVIATION 2.12 • n=7 Participants
|
27.5 kilograms per meter squared
STANDARD_DEVIATION 6.39 • n=5 Participants
|
|
Systolic Blood Pressure (mm Hg)
|
143.5 millimeters of Hg
STANDARD_DEVIATION 11.47 • n=5 Participants
|
127.3 millimeters of Hg
STANDARD_DEVIATION 12.74 • n=7 Participants
|
135.4 millimeters of Hg
STANDARD_DEVIATION 14.19 • n=5 Participants
|
|
Diastolic Blood Pressure (mm Hg)
|
91.3 millimeters of Hg
STANDARD_DEVIATION 18.63 • n=5 Participants
|
74.5 millimeters of Hg
STANDARD_DEVIATION 12.66 • n=7 Participants
|
82.9 millimeters of Hg
STANDARD_DEVIATION 17.25 • n=5 Participants
|
|
Pulse Rate (bpm)
|
74.5 beats per minute
STANDARD_DEVIATION 6.40 • n=5 Participants
|
74.3 beats per minute
STANDARD_DEVIATION 4.35 • n=7 Participants
|
74.4 beats per minute
STANDARD_DEVIATION 5.07 • n=5 Participants
|
|
Respiratory Rate (breaths per minute)
|
14.0 breaths per minute
STANDARD_DEVIATION 2.31 • n=5 Participants
|
17.5 breaths per minute
STANDARD_DEVIATION 1.00 • n=7 Participants
|
15.8 breaths per minute
STANDARD_DEVIATION 2.49 • n=5 Participants
|
|
SpO2 (%)
|
97.3 %
STANDARD_DEVIATION 0.96 • n=5 Participants
|
97.5 %
STANDARD_DEVIATION 1.91 • n=7 Participants
|
97.4 %
STANDARD_DEVIATION 1.41 • n=5 Participants
|
|
Temperature (degrees Celsius)
|
36.7 degrees Celsius
STANDARD_DEVIATION 0.37 • n=5 Participants
|
36.8 degrees Celsius
STANDARD_DEVIATION 0.27 • n=7 Participants
|
36.7 degrees Celsius
STANDARD_DEVIATION 0.30 • n=5 Participants
|
PRIMARY outcome
Timeframe: 8 hour period following dose of NKTR-181Population: Subjects who had sufficient MRI data for NKTR-181 or oxycodone IR treatment to allow for analysis of modulation of brain circuitry.
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).
Outcome measures
| Measure |
NKTR-181
n=4 Participants
Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR
|
Oxycodone IR 40 mg
n=4 Participants
One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181
|
|---|---|---|
|
Brain Activity Measured Via fMRI
Effective Connectivity between ACC and R Hippocampus at Baseline
|
0.0 Correlation Coefficient
Standard Deviation 0.12
|
0.2 Correlation Coefficient
Standard Deviation 0.34
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between ACC and R Hippocampus after 1 hour
|
0.0 Correlation Coefficient
Standard Deviation 0.28
|
0.0 Correlation Coefficient
Standard Deviation 0.21
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between ACC and R Hippocampus after 2 hours
|
0.1 Correlation Coefficient
Standard Deviation 0.20
|
-0.1 Correlation Coefficient
Standard Deviation 0.10
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between ACC and R Hippocampus after 4 hours
|
0.0 Correlation Coefficient
Standard Deviation 0.20
|
0.0 Correlation Coefficient
Standard Deviation 0.48
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between ACC and R Hippocampus after 8 hours
|
-0.1 Correlation Coefficient
Standard Deviation 0.02
|
0.2 Correlation Coefficient
Standard Deviation 0.07
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between R Amygdala and mPFC at Baseline
|
0.1 Correlation Coefficient
Standard Deviation 0.38
|
0.0 Correlation Coefficient
Standard Deviation 0.14
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between R Amygdala and mPFC after 1 hour
|
-0.2 Correlation Coefficient
Standard Deviation 0.41
|
0.1 Correlation Coefficient
Standard Deviation 0.34
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between R Amygdala and mPFC after 2 hours
|
0.2 Correlation Coefficient
Standard Deviation 0.21
|
0.4 Correlation Coefficient
Standard Deviation 0.51
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between R Amygdala and mPFC after 4 hours
|
0.2 Correlation Coefficient
Standard Deviation 0.26
|
0.1 Correlation Coefficient
Standard Deviation 0.21
|
|
Brain Activity Measured Via fMRI
Effective Connectivity between R Amygdala and mPFC after 8 hours
|
0.1 Correlation Coefficient
Standard Deviation 0.54
|
0.1 Correlation Coefficient
Standard Deviation 0.18
|
SECONDARY outcome
Timeframe: 24 hour period following dose administration Day 1 to 2Population: Subjects who received at least one dose of NKTR-181 or oxycodone IR and did not have unexpected pupillary dilation as a result of technical issues during the procedure.
Analysis of change in pupil diameter after administration of NKTR-181 or Oxycodone IR.
Outcome measures
| Measure |
NKTR-181
n=4 Participants
Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR
|
Oxycodone IR 40 mg
n=4 Participants
One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181
|
|---|---|---|
|
Change in Pupil Diameter Via Pupillometry
Baseline Pupil Diameter
|
4.45 millimeters
Standard Deviation 1.198
|
4.81 millimeters
Standard Deviation 1.717
|
|
Change in Pupil Diameter Via Pupillometry
Pupil Diameter After 1 Hour
|
5.03 millimeters
Standard Deviation 0.443
|
4.87 millimeters
Standard Deviation 1.624
|
|
Change in Pupil Diameter Via Pupillometry
Pupil Diameter After 2 Hours
|
4.82 millimeters
Standard Deviation 1.550
|
4.97 millimeters
Standard Deviation 1.747
|
|
Change in Pupil Diameter Via Pupillometry
Pupil Diameter After 4 Hours
|
4.34 millimeters
Standard Deviation 0.985
|
5.32 millimeters
Standard Deviation 1.723
|
|
Change in Pupil Diameter Via Pupillometry
Pupil Diameter After 6 Hours
|
3.99 millimeters
Standard Deviation 2.213
|
5.01 millimeters
Standard Deviation 1.086
|
|
Change in Pupil Diameter Via Pupillometry
Pupil Diameter After 8 Hours
|
4.28 millimeters
Standard Deviation 1.161
|
5.07 millimeters
Standard Deviation 1.115
|
|
Change in Pupil Diameter Via Pupillometry
Pupil Diameter After 12 Hours
|
4.91 millimeters
Standard Deviation NA
There is only one participant
|
3.87 millimeters
Standard Deviation NA
There is only one participant
|
|
Change in Pupil Diameter Via Pupillometry
Pupil Diameter After 24 Hours
|
4.61 millimeters
Standard Deviation 0.403
|
4.20 millimeters
Standard Deviation 0.191
|
SECONDARY outcome
Timeframe: 24 hour period following dose administration Day 1 to 2Population: Consisted of all subjects who had sufficient plasma concentration data to facilitate the calculation of maximum plasma drug concentration as determined by the pharmacokineticist.
Plasma drug concentration for NKTR-181 and Oxycodone IR over 24 hours.
Outcome measures
| Measure |
NKTR-181
n=4 Participants
Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR
|
Oxycodone IR 40 mg
n=4 Participants
One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181
|
|---|---|---|
|
Plasma Drug Concentration
Plasma Drug Concentration at Hour 1
|
1970 ng/mL
Standard Deviation 477
|
35.7 ng/mL
Standard Deviation 33.9
|
|
Plasma Drug Concentration
Plasma Drug Concentration at Hour 2
|
2360 ng/mL
Standard Deviation 1230
|
54.1 ng/mL
Standard Deviation 13.1
|
|
Plasma Drug Concentration
Plasma Drug Concentration at Hour 4
|
1350 ng/mL
Standard Deviation 656
|
46.7 ng/mL
Standard Deviation 15.3
|
|
Plasma Drug Concentration
Plasma Drug Concentration at Hour 8
|
388 ng/mL
Standard Deviation 230
|
27.1 ng/mL
Standard Deviation 7.47
|
|
Plasma Drug Concentration
Plasma Drug Concentration at Hour 12
|
185 ng/mL
Standard Deviation 30.4
|
14.8 ng/mL
Standard Deviation NA
Only one sample was collected for this measurement
|
|
Plasma Drug Concentration
Plasma Drug Concentration at Hour 24
|
63.5 ng/mL
Standard Deviation 13.7
|
3.9 ng/mL
Standard Deviation NA
Only one sample was collected for this measurement
|
SECONDARY outcome
Timeframe: 24 hour period following dose administration Day 1 to 2Population: Consisted of all subjects who had sufficient plasma concentration data to facilitate the calculation of the time to maximum plasma drug concentration as determined by the pharmacokineticist.
The amount of time needed for maximum drug concentration to be reached.
Outcome measures
| Measure |
NKTR-181
n=4 Participants
Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR
|
Oxycodone IR 40 mg
n=4 Participants
One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181
|
|---|---|---|
|
Time to Maximum Concentration (Tmax)
Plasma Drug Concentration at Hour 4
|
1350 ng/mL
Standard Deviation 656
|
46.7 ng/mL
Standard Deviation 15.3
|
|
Time to Maximum Concentration (Tmax)
Plasma Drug Concentration at Hour 8
|
388 ng/mL
Standard Deviation 230
|
27.1 ng/mL
Standard Deviation 7.47
|
|
Time to Maximum Concentration (Tmax)
Plasma Drug Concentration at Hour 1
|
1970 ng/mL
Standard Deviation 477
|
35.7 ng/mL
Standard Deviation 33.9
|
|
Time to Maximum Concentration (Tmax)
Plasma Drug Concentration at Hour 2
|
2360 ng/mL
Standard Deviation 1230
|
54.1 ng/mL
Standard Deviation 13.1
|
|
Time to Maximum Concentration (Tmax)
Plasma Drug Concentration at Hour 12
|
185 ng/mL
Standard Deviation 30.4
|
14.8 ng/mL
Standard Deviation NA
There is only one participant
|
|
Time to Maximum Concentration (Tmax)
Plasma Drug Concentration at Hour 24
|
63.5 ng/mL
Standard Deviation 13.7
|
3.9 ng/mL
Standard Deviation NA
There is only one participant
|
|
Time to Maximum Concentration (Tmax)
Time to Maximum Concentration (Tmax) measured in hours
|
1.54 ng/mL
Standard Deviation 0.676
|
2.21 ng/mL
Standard Deviation 1.02
|
SECONDARY outcome
Timeframe: 19 daysPopulation: Consisted of all subjects who received at least 1 dose of NKTR-181 or Oxycodone IR.
Number of patients who experienced any type of adverse event as a result of one of the treatments.
Outcome measures
| Measure |
NKTR-181
n=4 Participants
Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR
|
Oxycodone IR 40 mg
n=4 Participants
One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181
|
|---|---|---|
|
Treatment-Emergent Adverse Events (TEAEs)
|
1 Participants
|
0 Participants
|
Adverse Events
NKTR-181
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Oxycodone IR 40 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
NKTR-181
n=4 participants at risk
Two 200 mg NKTR-181 tablets and 1 placebo capsule for oxycodone IR
|
Oxycodone IR 40 mg
n=4 participants at risk
One capsule of Oxycodone IR 40 mg and 2 placebo tablets for NKTR-181
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
25.0%
1/4 • Number of events 1 • 19 days post-dose of NKTR-181 or Oxycodone IR 40 mg
All adverse events and their duration were listed. Adverse events that occurred on or after study dose administration were summarized. Verbatim terms were mapped to PTs and system organ classes (SOC) using the Medical Dictionary for Regulatory Activities (MedDRA).
|
0.00%
0/4 • 19 days post-dose of NKTR-181 or Oxycodone IR 40 mg
All adverse events and their duration were listed. Adverse events that occurred on or after study dose administration were summarized. Verbatim terms were mapped to PTs and system organ classes (SOC) using the Medical Dictionary for Regulatory Activities (MedDRA).
|
|
General disorders
Insomnia
|
25.0%
1/4 • Number of events 1 • 19 days post-dose of NKTR-181 or Oxycodone IR 40 mg
All adverse events and their duration were listed. Adverse events that occurred on or after study dose administration were summarized. Verbatim terms were mapped to PTs and system organ classes (SOC) using the Medical Dictionary for Regulatory Activities (MedDRA).
|
0.00%
0/4 • 19 days post-dose of NKTR-181 or Oxycodone IR 40 mg
All adverse events and their duration were listed. Adverse events that occurred on or after study dose administration were summarized. Verbatim terms were mapped to PTs and system organ classes (SOC) using the Medical Dictionary for Regulatory Activities (MedDRA).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee There are restrictions to the PI's rights to discuss or publish trial results.
- Publication restrictions are in place
Restriction type: OTHER