Trial Outcomes & Findings for Xyrem and Brain Dopamine in Narcolepsy (NCT NCT02637076)
NCT ID: NCT02637076
Last Updated: 2021-03-23
Results Overview
BPND (Binding Potential) of \[C-11\]raclopride measures 1 hour after taking a single 3g dose of Xyrem.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
17 participants
Primary outcome timeframe
1 hour post Xyrem
Results posted on
2021-03-23
Participant Flow
Participant milestones
| Measure |
Narcolepsy With Cataplexy
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
Overall Study
STARTED
|
2
|
15
|
|
Overall Study
COMPLETED
|
1
|
10
|
|
Overall Study
NOT COMPLETED
|
1
|
5
|
Reasons for withdrawal
| Measure |
Narcolepsy With Cataplexy
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
Overall Study
due to technical difficulties, the 1 hour post PET scan was not completed at the one hour time point
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
4
|
Baseline Characteristics
Xyrem and Brain Dopamine in Narcolepsy
Baseline characteristics by cohort
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52 years
n=5 Participants
|
29.6 years
STANDARD_DEVIATION 8 • n=7 Participants
|
31.6 years
STANDARD_DEVIATION 10 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
6 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
|
1 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
11 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
|
6 Participants
n=7 Participants
|
6 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 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
|
|
Region of Enrollment
Canada
|
1 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
[C-11]raclopride BPND at Baseline
Limbic Striatum
|
2.59 BPND (Binding Potential)
n=5 Participants
|
2.83 BPND (Binding Potential)
STANDARD_DEVIATION 0.19 • n=7 Participants
|
2.80 BPND (Binding Potential)
STANDARD_DEVIATION 0.19 • n=5 Participants
|
|
[C-11]raclopride BPND at Baseline
Associative Striatum
|
3.06 BPND (Binding Potential)
n=5 Participants
|
3.63 BPND (Binding Potential)
STANDARD_DEVIATION 0.32 • n=7 Participants
|
3.58 BPND (Binding Potential)
STANDARD_DEVIATION 0.35 • n=5 Participants
|
|
[C-11]raclopride BPND at Baseline
Sensorimotor Striatum
|
3.11 BPND (Binding Potential)
n=5 Participants
|
4.04 BPND (Binding Potential)
STANDARD_DEVIATION 0.43 • n=7 Participants
|
3.96 BPND (Binding Potential)
STANDARD_DEVIATION 0.49 • n=5 Participants
|
|
[C-11]DTBZ BPND at Baseline
Limbic Striatum
|
1.68 BPND (Binding Potential)
n=5 Participants
|
1.85 BPND (Binding Potential)
STANDARD_DEVIATION 0.19 • n=7 Participants
|
1.84 BPND (Binding Potential)
STANDARD_DEVIATION 0.18 • n=5 Participants
|
|
[C-11]DTBZ BPND at Baseline
Associative Striatum
|
2.41 BPND (Binding Potential)
n=5 Participants
|
2.60 BPND (Binding Potential)
STANDARD_DEVIATION 0.26 • n=7 Participants
|
2.58 BPND (Binding Potential)
STANDARD_DEVIATION 0.25 • n=5 Participants
|
|
[C-11]DTBZ BPND at Baseline
Sensorimotor Striatum
|
2.49 BPND (Binding Potential)
n=5 Participants
|
3.05 BPND (Binding Potential)
STANDARD_DEVIATION 0.38 • n=7 Participants
|
3.00 BPND (Binding Potential)
STANDARD_DEVIATION 0.40 • n=5 Participants
|
PRIMARY outcome
Timeframe: 1 hour post XyremBPND (Binding Potential) of \[C-11\]raclopride measures 1 hour after taking a single 3g dose of Xyrem.
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
[C-11]Raclopride BPND at 1 Hour Post Xyrem
Limbic Striatum
|
2.94 BPND (Binding Potential)
|
3.01 BPND (Binding Potential)
Standard Deviation 0.28
|
|
[C-11]Raclopride BPND at 1 Hour Post Xyrem
Associate Striatum
|
3.80 BPND (Binding Potential)
|
3.70 BPND (Binding Potential)
Standard Deviation 0.33
|
|
[C-11]Raclopride BPND at 1 Hour Post Xyrem
Sensorimotor Striatum
|
3.87 BPND (Binding Potential)
|
4.11 BPND (Binding Potential)
Standard Deviation 0.49
|
PRIMARY outcome
Timeframe: 1 hour post Xyrem\[C-11\] raclopride is a radioligand that binds to the D2/3 dopamine receptor in the dopamine-rich striatum and which is sensitive to dopamine occupancy. % change was calculated as follows: (1 hour BPND - baseline BPND)/baseline BPND \*100; Mean % change represents the mean of each participant's individual % change within the group.
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem
Limbic Stiatum
|
13.27 percentage change from baseline
|
6.49 percentage change from baseline
Standard Deviation 8.60
|
|
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem
Associative Striatum
|
23.88 percentage change from baseline
|
2.11 percentage change from baseline
Standard Deviation 8.59
|
|
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem
Sensorimotor Striatum
|
24.43 percentage change from baseline
|
1.93 percentage change from baseline
Standard Deviation 8.85
|
PRIMARY outcome
Timeframe: 7 hours post XyremBPND (Binding Potential) of \[C-11\]raclopride measures 7 hours after taking a single 3g dose of Xyrem.
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
[C-11]Raclopride BPND at 7 Hours Post Xyrem
Associate Striatum
|
2.83 BPND (Binding Potential)
|
3.62 BPND (Binding Potential)
Standard Deviation 0.29
|
|
[C-11]Raclopride BPND at 7 Hours Post Xyrem
Limbic Striatum
|
2.33 BPND (Binding Potential)
|
2.76 BPND (Binding Potential)
Standard Deviation 0.18
|
|
[C-11]Raclopride BPND at 7 Hours Post Xyrem
Sensorimotor Striatum
|
2.75 BPND (Binding Potential)
|
4.06 BPND (Binding Potential)
Standard Deviation 0.40
|
PRIMARY outcome
Timeframe: 7 hours post Xyrem\[C-11\] raclopride is a radioligand that binds to the D2/3 dopamine receptor in the dopamine-rich striatum and which is sensitive to dopamine occupancy. % change was calculated as follows: (7 hours BPND - baseline BPND)/baseline BPND \*100; Mean % change represents the mean of each participant's individual % change within the group.
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem
Associative Striatum
|
-7.50 percentage change from baseline
|
0.17 percentage change from baseline
Standard Deviation 7.42
|
|
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem
Sensorimotor Striatum
|
-11.56 percentage change from baseline
|
0.72 percentage change from baseline
Standard Deviation 7.64
|
|
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem
Limbic Striatum
|
-10.13 percentage change from baseline
|
-2.07 percentage change from baseline
Standard Deviation 8.24
|
SECONDARY outcome
Timeframe: 5 hours post single Xyrem doseMeasurement of \[C-11\]DTBZ 5 hours after taking a single dose of 3g Xyrem
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
[C-11]DTBZ BPND at 5 Hours Post Xyrem
Limbic Striatum
|
1.71 BPND (binding potential)
|
1.82 BPND (binding potential)
Standard Deviation 0.24
|
|
[C-11]DTBZ BPND at 5 Hours Post Xyrem
Associative Striatum
|
2.56 BPND (binding potential)
|
2.65 BPND (binding potential)
Standard Deviation 0.40
|
|
[C-11]DTBZ BPND at 5 Hours Post Xyrem
Sensorimotor Striatum
|
2.65 BPND (binding potential)
|
3.12 BPND (binding potential)
Standard Deviation 0.53
|
SECONDARY outcome
Timeframe: 5 hours post single Xyrem dose\[C-11\] DTBZ is a radioligand that binds to the vesicular monoamine transporter and which is sensitive to dopamine occupancy. % change was calculated as follows: (5 hour BPND - baseline BPND)/baseline BPND \*100; Mean % change represents the mean of each participant's individual % change within the group.
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
% Change in PET [C-11] Dihydrotetrabenazine (DTBZ) Binding From Baseline to Five Hours Post Xyrem
Limbic Striatum
|
2.00 percentage change from baseline
|
-1.98 percentage change from baseline
Standard Deviation 9.20
|
|
% Change in PET [C-11] Dihydrotetrabenazine (DTBZ) Binding From Baseline to Five Hours Post Xyrem
Associative Striatum
|
6.10 percentage change from baseline
|
2.04 percentage change from baseline
Standard Deviation 11.84
|
|
% Change in PET [C-11] Dihydrotetrabenazine (DTBZ) Binding From Baseline to Five Hours Post Xyrem
Sensorimotor Striatum
|
6.51 percentage change from baseline
|
2.47 percentage change from baseline
Standard Deviation 12.09
|
SECONDARY outcome
Timeframe: multiple time points from 0 to 7 hours post-XyremThe concentration of gammahydroxybutyrate in blood of participants who have received a single dose of Xyrem, as measured by Area Under the Curve.
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
Blood Gamma-hydroxybutyrate (GHB) Concentration (AUC)
|
187.03 AUC (ug/ml*hr)
|
178.49 AUC (ug/ml*hr)
Standard Deviation 52.12
|
SECONDARY outcome
Timeframe: multiple time points from 0 to 7 hours post-XyremThe concentration of gammahydroxybutyrate in blood of participants who have received a single dose of Xyrem as measured by Cmax.
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
Blood Gamma-hydroxybutyrate (GHB) Cmax
|
107 mg/ml
|
107.37 mg/ml
Standard Deviation 32.95
|
SECONDARY outcome
Timeframe: observed after receiving single dose of Xyrem, up to 9 hoursPeriod of time when the participant was experiencing the sedative action of Xyrem. Data derived from self-report as well as anesthesiologist observation.
Outcome measures
| Measure |
Narcolepsy With Cataplexy
n=1 Participants
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=10 Participants
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
Duration of Drowsiness
|
220.20 minutes
|
92.4 minutes
Interval 10.02 to 285.0
|
Adverse Events
Narcolepsy With Cataplexy
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Healthy Controls
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Narcolepsy With Cataplexy
n=2 participants at risk
patients given single dose of Xyrem
Xyrem: single 3.0 gram dose
|
Healthy Controls
n=15 participants at risk
healthy controls given a single dose of Xyrem
Xyrem: single 3.0 gram dose
|
|---|---|---|
|
General disorders
Euphoria
|
0.00%
0/2 • Adverse events will be assessed at each study visit following administration of the first PET radiotracer until the follow-up phone after Xyrem administration (2 visits plus 1 follow-up phone call), an average of 10 days per participant.
|
6.7%
1/15 • Number of events 1 • Adverse events will be assessed at each study visit following administration of the first PET radiotracer until the follow-up phone after Xyrem administration (2 visits plus 1 follow-up phone call), an average of 10 days per participant.
|
|
General disorders
Nausea
|
0.00%
0/2 • Adverse events will be assessed at each study visit following administration of the first PET radiotracer until the follow-up phone after Xyrem administration (2 visits plus 1 follow-up phone call), an average of 10 days per participant.
|
20.0%
3/15 • Number of events 3 • Adverse events will be assessed at each study visit following administration of the first PET radiotracer until the follow-up phone after Xyrem administration (2 visits plus 1 follow-up phone call), an average of 10 days per participant.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place