Trial Outcomes & Findings for Treatment of Hyperphagia Behavioral Symptoms in Children and Adults Diagnosed With Prader-Willi Syndrome (NCT NCT01968187)

NCT ID: NCT01968187

Last Updated: 2025-03-27

Results Overview

The HPWSQ-R is an 11-item questionnaire examining the psychological, developmental, and neurobiological correlates of hyperphagia in PWS. The items are classified into 3 domains; behavior, drive, and severity with each item rated on a five-point scale (1: not at all/none of the time/extremely easy to 5: extremely/all of the time/extremely hard). The questionnaire was completed by the parent/caregiver using a 1-week recall period. Total score was the sum of all the items in the three domains and ranged from 11 (no hyperphagia behaviors) to 55 (most severe hyperphagia behaviors). Change from baseline in HPWSQ-R Total Score at Day 15 is presented for this outcome measure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

From Day 1 (baseline) to Day 15

Results posted on

2025-03-27

Participant Flow

The trial was performed in the United States, and a total of 3 sites randomized subjects to the trial between Jan 2014 to Jul 2014.

In total, 38 subjects were screened and randomized. One subject in the Carbetocin (FE 992097) arm was randomized in error and did not receive the investigational medicinal product (IMP), and was listed as a screening failure. Of the randomized subjects, 37 subjects were exposed to IMP: 17 to Carbetocin (FE 992097) and 20 to placebo.

Participant milestones

Participant milestones
Measure	Carbetocin (FE 992097) Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.
Overall Study STARTED	18	20
Overall Study Treated	17	20
Overall Study COMPLETED	17	19
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Carbetocin (FE 992097) Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.
Overall Study Adverse Event	0	1
Overall Study Randomized but not treated	1	0

Baseline Characteristics

Treatment of Hyperphagia Behavioral Symptoms in Children and Adults Diagnosed With Prader-Willi Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carbetocin (FE 992097) n=17 Participants Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo n=20 Participants Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Total n=37 Participants Total of all reporting groups
Age, Continuous	13.9 years STANDARD_DEVIATION 2.45 • n=39 Participants	13.6 years STANDARD_DEVIATION 2.52 • n=41 Participants	13.7 years STANDARD_DEVIATION 2.46 • n=35 Participants
Sex: Female, Male Female	11 Participants n=39 Participants	12 Participants n=41 Participants	23 Participants n=35 Participants
Sex: Female, Male Male	6 Participants n=39 Participants	8 Participants n=41 Participants	14 Participants n=35 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=39 Participants	19 Participants n=41 Participants	36 Participants n=35 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Asian	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Black or African American	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Race (NIH/OMB) White	17 Participants n=39 Participants	19 Participants n=41 Participants	36 Participants n=35 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Baseline Body Mass Index (BMI)	25.72 kg/m^2 STANDARD_DEVIATION 5.947 • n=39 Participants	25.66 kg/m^2 STANDARD_DEVIATION 7.537 • n=41 Participants	25.69 kg/m^2 STANDARD_DEVIATION 6.760 • n=35 Participants

PRIMARY outcome

Timeframe: From Day 1 (baseline) to Day 15

Population: The analysis population included the full analysis set (FAS) which consisted of all subjects in the safety population who had the primary efficacy endpoint measured (at baseline and phone call \[Day 8\] ±1 or Day 15). Analyses for the FAS were conducted according to the randomized treatment.

Outcome measures

Outcome measures
Measure	Carbetocin (FE 992097) n=17 Participants Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo n=20 Participants Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.
Change From Baseline in Hyperphagia in Prader-Willi Syndrome (PWS) Questionnaires- Responsiveness (HPWSQ-R) Total Score at End-of-treatment (Day 15)	-15.6 score on a scale Standard Error 3.06	-8.9 score on a scale Standard Error 2.61

SECONDARY outcome

Timeframe: At Day 15

The Clinical Global Impression (CGI) scale consists of a 7-point clinician rating of illness severity (1 = normal, not at all ill, 7 = among the most extremely ill patients), at the beginning of the trial (baseline) - Clinical Global Impression-Severity Rating (CGI-S) and a 7-point clinician rating of improvement of patient condition (1=very much improved since baseline/initiation of treatment, 7=very much worse from baseline), during and at the end of the trial (Day 15) - CGI-I. The CGI-I score at Day 15 is presented for this outcome measure.

Outcome measures

Outcome measures
Measure	Carbetocin (FE 992097) n=16 Participants Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo n=19 Participants Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.
Clinical Global Impression- Improvement After Treatment (CGI-I) Score at End-of-treatment (Day 15)	2.7 score on a scale Standard Error 0.49	3.6 score on a scale Standard Error 0.43

SECONDARY outcome

Timeframe: From Day 1 (baseline) to Day 15

Population: The analysis population included the FAS which consisted of all subjects in the safety population who had the primary efficacy endpoint measured (at baseline and phone call \[Day 8\] ±1 or Day 15). Analyses for the FAS were conducted according to the randomized treatment.

The HPWSQ-R is an 11-item questionnaire examining the psychological, developmental, and neurobiological correlates of hyperphagia in PWS. The items were classified into 3 domains; behavior, drive, and severity with each item rated on a five-point score range from 1 (not at all/none of the time/extremely easy) to 5 (extremely/all of the time/extremely hard). The questionnaire was completed by the parent/caregiver using a 1-week recall period. Changes in the HPWSQ-R Total Score and in the Domain Scores (behavior, drive, and severity) at Day 15 is presented for this outcome measure. HPWSQ-R Behavior, Drive and Severity scores range from 5-25, 4-20, and 2-10, respectively, with higher scores indicating a worse outcome. Change from baseline is presented = (Day 15 score minus Baseline score).

Outcome measures

Outcome measures
Measure	Carbetocin (FE 992097) n=17 Participants Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo n=20 Participants Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.
Change From Baseline in HPWSQ-R Domain Scores (Behavior, Drive and Severity) at End-of-treatment (Day 15) Behavior	-5.9 score on a scale Interval -16.0 to 3.0	-3.9 score on a scale Interval -14.0 to 3.0
Change From Baseline in HPWSQ-R Domain Scores (Behavior, Drive and Severity) at End-of-treatment (Day 15) Drive	-4.5 score on a scale Interval -13.0 to 3.0	-2.9 score on a scale Interval -16.0 to 3.0
Change From Baseline in HPWSQ-R Domain Scores (Behavior, Drive and Severity) at End-of-treatment (Day 15) Severity	-3.3 score on a scale Interval -7.0 to 2.0	-1.8 score on a scale Interval -7.0 to 3.0

SECONDARY outcome

Timeframe: From Day 1 (baseline) to Day 15

The CY-BOCS is a clinician rated, semi-structured inventory of specific symptoms and symptom severity in pediatric obsessive-compulsive disorder (OCD). Total scores on the CY-BOCS are calculated using a symptom checklist and severity scale. The 10 severity items are summed to produce an Obsessions Severity Score (5 items), Compulsions Severity Score (5 items), and Total score (sum of all 10 severity items). The total score is calculated by summing the 10 individual scores and ranges from 0 (no obsessions or compulsions) to 40 (most severe OC).

Outcome measures

Outcome measures
Measure	Carbetocin (FE 992097) n=16 Participants Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo n=19 Participants Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.
Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale Score (CY-BOCS) at End-of-treatment (Day 15)	-8.8 score on a scale Standard Error 2.29	-2.6 score on a scale Standard Error 1.82

SECONDARY outcome

Timeframe: From Day 1 (baseline) to Day 15

The Food Domain Score of the Reiss Profile consisted of 7 questions that pertain to food seeking behavior. The questions were rated on a five point scale ranging from -2 (strongly disagree; this phrase is not at all characteristic of the person) to 2 (strongly agree; this phrase is definitely characteristic of the person). Total score was defined as the sum of all individual item scores. The total score ranged from -14 to 14 with higher scores indicating higher severity. Change from baseline in Food Domain of the Reiss Profile at Day 15 is presented for this outcome measure.

Outcome measures

Outcome measures
Measure	Carbetocin (FE 992097) n=16 Participants Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo n=19 Participants Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.
Change From Baseline in the Food Domain Score of the Reiss Profile at End-of-treatment (Day 15)	-6.9 score on a scale Standard Error 1.94	-2.5 score on a scale Standard Error 1.55

Adverse Events

Carbetocin (FE 992097)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Global Clinical Compliance

Ferring Pharmaceuticals

Phone: +1 862-286-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
Publication restrictions are in place

Restriction type: OTHER

Measure	Carbetocin (FE 992097) n=17 participants at risk Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.	Placebo n=20 participants at risk Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days.
Gastrointestinal disorders Abdominal pain upper	5.9% 1/17 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Gastrointestinal disorders Diarrhea	5.9% 1/17 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	0.00% 0/20 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Infections and infestations Conjunctivitis infective	5.9% 1/17 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	0.00% 0/20 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Infections and infestations Sinusitis	0.00% 0/17 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Injury, poisoning and procedural complications Medication error	5.9% 1/17 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	10.0% 2/20 • Number of events 2 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/17 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/17 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Investigations Urine analysis abnormal	0.00% 0/17 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Metabolism and nutrition disorders Hyperphagia	0.00% 0/17 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Nervous system disorders Headache	29.4% 5/17 • Number of events 8 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	30.0% 6/20 • Number of events 18 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Nervous system disorders Dysgeusia	5.9% 1/17 • Number of events 9 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	0.00% 0/20 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Psychiatric disorders Aggression	0.00% 0/17 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Psychiatric disorders Agitation	0.00% 0/17 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/17 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	5.0% 1/20 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Respiratory, thoracic and mediastinal disorders Sneezing	5.9% 1/17 • Number of events 2 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	0.00% 0/20 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Respiratory, thoracic and mediastinal disorders Throat irritation	5.9% 1/17 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	0.00% 0/20 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Vascular disorders Flushing	5.9% 1/17 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	0.00% 0/20 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
Psychiatric disorders Sleep Disorder	5.9% 1/17 • Number of events 1 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.	0.00% 0/20 • The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call. Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.