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

A Prospective, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Effectiveness of Intranasal Carbetocin in Subjects With Prader-Willi Syndrome (PWS)

The purpose of this study is to evaluate the safety and effectiveness of intranasal FE 992097 in children and adults with Prader-Willi Syndrome.

Study Overview

• Status: Completed
• Conditions: Hyperphagia in Prader-Willi Syndrome
• Intervention / Treatment: Drug: FE 992097; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States
      • Florida University
  • New York
    • Mineola, New York, United States
      • Winthrop University
  • Tennessee
    • Nashville, Tennessee, United States
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female 10-18 years of age (both inclusive)
• Genetically confirmed diagnosis of Prader-Willi Syndrome
• Determined to be in nutritional phase 3 Prader-Willi Syndrome based on Miller et al, 2011

Exclusion Criteria:

• Known genetic, hormonal, or chromosomal cause of cognitive impairment other than Prader-Willi Syndrome
• Presence of currently active psychotic symptoms
• Presence of any cardiovascular disorders, epilepsy, frequent migraines or severe asthma
• Previous diagnosis of autism spectrum disorder by a qualified healthcare provider
• Prior or concomitant use of a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI), antipsychotic medication, wakefulness-promoting drug, or thyroid hormone unless dosage has been stable ≥6 months at time of screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: 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.
Experimental: Carbetocin (FE 992097)	Drug: FE 992097; Each spray pump actuation delivered a 50 μL volume of solution that contained 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril that delivered 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hyperphagia in Prader-Willi Syndrome (PWS) Questionnaires- Responsiveness (HPWSQ-R) Total Score at End-of-treatment (Day 15)	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.	From Day 1 (baseline) to Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression- Improvement After Treatment (CGI-I) Score at End-of-treatment (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.	At Day 15
Change From Baseline in HPWSQ-R Domain Scores (Behavior, Drive and Severity) at End-of-treatment (Day 15)	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).	From Day 1 (baseline) to Day 15
Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale Score (CY-BOCS) at End-of-treatment (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).	From Day 1 (baseline) to Day 15
Change From Baseline in the Food Domain Score of the Reiss Profile at End-of-treatment (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.	From Day 1 (baseline) to Day 15

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Clinical Development Support, Ferring Pharmaceuticals

Publications and helpful links

General Publications

• Dykens EM, Miller J, Angulo M, Roof E, Reidy M, Hatoum HT, Willey R, Bolton G, Korner P. Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome. JCI Insight. 2018 Jun 21;3(12):e98333. doi: 10.1172/jci.insight.98333. eCollection 2018 Jun 21.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2014
• Primary Completion (Actual): July 16, 2014
• Study Completion (Actual): July 16, 2014

Study Registration Dates

• First Submitted: October 9, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimated): October 23, 2013

Study Record Updates

• Last Update Posted (Actual): March 27, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Imprinting Disorders; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Nutrition Disorders; Genetic Diseases, Inborn; Overnutrition; Signs and Symptoms, Digestive; Disease; Neurobehavioral Manifestations; Congenital Abnormalities; Abnormalities, Multiple; Overweight; Intellectual Disability; Obesity; Chromosome Disorders; Syndrome; Prader-Willi Syndrome; Hyperphagia
• Other Study ID Numbers: 000114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes