Trial Outcomes & Findings for A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension (NCT NCT04257929)
NCT ID: NCT04257929
Last Updated: 2026-01-14
Results Overview
Change in Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score from Baseline to Week 11 for pitolisant compared with placebo. The score of the ESS-CHAD ranges from 0 to 24. A decrease in score represents an improvement in excessive daytime sleepiness.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
65 participants
Primary outcome timeframe
Baseline to Week 11
Results posted on
2026-01-14
Participant Flow
Participant milestones
| Measure |
Double-Blind Treatment Phase Lower Dose Pitolisant
Stable pitolisant doses of 8.9 mg, 13.35 mg, or 17.8 mg based on age
|
Double-Blind Treatment Phase Higher Dose Pitolisant
Stable pitolisant doses of 17.8 mg, 26.7 mg, or 35.6 mg based on age
|
Double-Blind Treatment Phase Placebo
Matching placebo tablets
|
|---|---|---|---|
|
Overall Study
STARTED
|
20
|
22
|
23
|
|
Overall Study
COMPLETED
|
18
|
21
|
20
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
3
|
Reasons for withdrawal
| Measure |
Double-Blind Treatment Phase Lower Dose Pitolisant
Stable pitolisant doses of 8.9 mg, 13.35 mg, or 17.8 mg based on age
|
Double-Blind Treatment Phase Higher Dose Pitolisant
Stable pitolisant doses of 17.8 mg, 26.7 mg, or 35.6 mg based on age
|
Double-Blind Treatment Phase Placebo
Matching placebo tablets
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
|
Overall Study
COVID-19
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
Baseline Characteristics
A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension
Baseline characteristics by cohort
| Measure |
Double-Blind Treatment Phase Lower Dose Pitolisant
n=20 Participants
Stable pitolisant doses of 8.9 mg, 13.35 mg, or 17.8 mg based on age
|
Double-Blind Treatment Phase Higher Dose Pitolisant
n=22 Participants
Stable pitolisant doses of 17.8 mg, 26.7 mg, or 35.6 mg based on age
|
Double-Blind Treatment Phase Placebo
n=23 Participants
Matching placebo tablets
|
Total
n=65 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
12.1 years
STANDARD_DEVIATION 5.44 • n=14 Participants
|
13.1 years
STANDARD_DEVIATION 6.70 • n=10 Participants
|
11.9 years
STANDARD_DEVIATION 4.31 • n=24 Participants
|
12.4 years
STANDARD_DEVIATION 5.50 • n=78 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=14 Participants
|
12 Participants
n=10 Participants
|
9 Participants
n=24 Participants
|
32 Participants
n=78 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=14 Participants
|
10 Participants
n=10 Participants
|
14 Participants
n=24 Participants
|
33 Participants
n=78 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=14 Participants
|
2 Participants
n=10 Participants
|
2 Participants
n=24 Participants
|
4 Participants
n=78 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
20 Participants
n=14 Participants
|
20 Participants
n=10 Participants
|
21 Participants
n=24 Participants
|
61 Participants
n=78 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=14 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=78 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=14 Participants
|
22 participants
n=10 Participants
|
23 participants
n=24 Participants
|
65 participants
n=78 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 11Population: The efficacy population was the modified Intent-to-Treat (mITT) Population, which included all randomized patients who received at least 1 dose of study drug and had both a Baseline assessment and at least 1 post Baseline assessment for a given endpoint analysis during the Double-Blind Treatment Phase.
Change in Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score from Baseline to Week 11 for pitolisant compared with placebo. The score of the ESS-CHAD ranges from 0 to 24. A decrease in score represents an improvement in excessive daytime sleepiness.
Outcome measures
| Measure |
Double-Blind Treatment Phase Lower Dose Pitolisant
n=19 Participants
Stable pitolisant doses of 8.9 mg, 13.35 mg, or 17.8 mg based on age
|
Double-Blind Treatment Phase Higher Dose Pitolisant
n=22 Participants
Stable pitolisant doses of 17.8 mg, 26.7 mg, or 35.6 mg based on age
|
Double-Blind Treatment Phase Placebo
n=21 Participants
Matching placebo tablets
|
|---|---|---|---|
|
Excessive Daytime Sleepiness
|
-3.5 score on a scale
Standard Error 1.14
|
-5.0 score on a scale
Standard Error 1.07
|
-3.9 score on a scale
Standard Error 1.08
|
SECONDARY outcome
Timeframe: Baseline to Week 11Change in Caregiver Global Impression of Severity for Excessive Daytime Sleepiness. The Caregiver Global Impression of Severity for Excessive Daytime Sleepiness is a five-item scale that ranges from "not at all" to "very high likelihood." An assessment of being less likely to fall asleep represents an improvement in the caregiver's overall impression of the patient's excessive daytime sleepiness.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 11Change in Clinical Global Impression of Severity of Overall Clinical Status. The Clinical Global Impression of Severity of Overall Clinical Status is a four-item scale that ranges from "normal" to "severely symptomatic." An assessment of less severe symptoms represents an improvement in the clinician's perception of the overall clinical status related to PWS.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 11Change in Aberrant Behavior Checklist, Second Edition. The Aberrant Behavior Checklist-Community, Second Edition, rates 58 specific symptoms on a four-item scale ranging from "not at all a problem" to "the problem is severe in degree." A decrease in score represents an improvement in the caregiver's impression in the patient's problematic behavior.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 11Change in Montefiore-Einstein Rigidity Scale - Prader-Willi Syndrome (MERS-R-PWS). The MERS-R-PWS is a clinician-rated, semi-structured interview conducted with both the patient with PWS and caregiver present. The MERS-R-PWS measures three domains of rigid behavior - behavior, cognitive, and protest. Within each domain, four items are rated on a scale ranging from 0 to 4. A decrease in score represents an improvement in rigid behavior.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 11Change in Cogstate Detection Test. The Cogstate Detection Test is a computerized test. Accuracy with a faster speed represents an improvement in psychomotor test performance.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 11Change in Cogstate Identification Test. The Cogstate Identification Test is a computerized test. Accuracy with a faster speed represents an improvement in attention test performance.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 11Change in Cogstate One Back Test. The Cogstate One Back Test is a computerized test. Accuracy with a faster speed represents a better working memory test performance.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 11Change in 22-Item Zarit Burden Interview. The Zarit Burden Interview is a self-reported questionnaire in which caregivers are asked to rate their experience on a five-item scale (0 = "never" and 4 = "nearly always") for 22 questions related to caregiver health and psychological well-being, finances, impact on social life, and relationship with the patient with PWS. A decrease in score represents an improvement in the caregiver's perceived burden.
Outcome measures
Outcome data not reported
Adverse Events
Double-Blind Treatment Phase Lower Dose Pitolisant
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Double-Blind Treatment Phase Higher Dose Pitolisant
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Double-Blind Treatment Phase Placebo
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Double-Blind Treatment Phase Lower Dose Pitolisant
n=20 participants at risk
Stable pitolisant doses of 8.9 mg, 13.35 mg, or 17.8 mg based on age
|
Double-Blind Treatment Phase Higher Dose Pitolisant
n=22 participants at risk
Stable pitolisant doses of 17.8 mg, 26.7 mg, or 35.6 mg based on age
|
Double-Blind Treatment Phase Placebo
n=23 participants at risk
Matching placebo tablets
|
|---|---|---|---|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
0.00%
0/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
4.3%
1/23 • Number of events 1 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
Other adverse events
| Measure |
Double-Blind Treatment Phase Lower Dose Pitolisant
n=20 participants at risk
Stable pitolisant doses of 8.9 mg, 13.35 mg, or 17.8 mg based on age
|
Double-Blind Treatment Phase Higher Dose Pitolisant
n=22 participants at risk
Stable pitolisant doses of 17.8 mg, 26.7 mg, or 35.6 mg based on age
|
Double-Blind Treatment Phase Placebo
n=23 participants at risk
Matching placebo tablets
|
|---|---|---|---|
|
Psychiatric disorders
Anxiety
|
20.0%
4/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
4.5%
1/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
8.7%
2/23 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
|
Psychiatric disorders
Irritability
|
20.0%
4/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
4.5%
1/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
4.3%
1/23 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
|
Psychiatric disorders
Sleep disorder
|
10.0%
2/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
0.00%
0/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
0.00%
0/23 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
2/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
9.1%
2/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
4.3%
1/23 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
|
Infections and infestations
COVID-19
|
0.00%
0/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
13.6%
3/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
8.7%
2/23 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
|
Nervous system disorders
Headache
|
15.0%
3/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
9.1%
2/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
8.7%
2/23 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.0%
2/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
0.00%
0/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
0.00%
0/23 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
|
Metabolism and nutrition disorders
Hyperphagia
|
10.0%
2/20 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
4.5%
1/22 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
8.7%
2/23 • Data are presented for adverse events occurring after first dose of study drug and up to 30 days after the date of last dose of study drug, for a total of up to 15 weeks.
Data are presented herein for TEAEs. A TEAE is defined as any new adverse event or any worsening of a pre-existing condition that is reported after first dose of study drug and up to 30 days after the date of last dose of study drug.
|
Additional Information
Sharon Wolfe-Schwartz, Executive Director, Medical and RegulatoryWriting
Harmony Biosciences
Phone: 267-965-0270
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place