Study of Carbetocin Nasal Spray for the Treatment of Hyperphagia in Prader-Willi Syndrome

Study Overview
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Brief Summary
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12-week, randomized, double-blind, placebo-controlled, parallel-group study of carbetocin nasal spray for the treatment of hyperphagia in Prader-Willi syndrome (PWS)

Detailed Description
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This is a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing carbetocin nasal spray 3.2 mg TID with placebo (matched placebo nasal spray TID) in subjects with PWS.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Carbetocin Nasal Spray for the Treatment of Hyperphagia in Prader-Willi Syndrome

Conditions
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Hyperphagia in Prader-Willi Syndrome

Intervention / Treatment
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* Drug: Carbetocin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female and 5 through 30 years of age Prader-Willi syndrome with a documented disease-causing mutation Increased appetite with decreased satiety accompanied by food seeking (consistent with PWS Nutritional Phase 3) HQ-CT total score of ≥13 at Screening and Baseline CGI-S score for hyperphagia in PWS of ≥4 at Screening and Baseline Lives with a caregiver who understands and is willing and able to adhere to study-related procedures and is willing to participate in all study visits Exclusion Criteria: Genetically diagnosed with Schaaf-Yang syndrome or another genetic, hormonal, or chromosomal cognitive impairment besides PWS An active upper respiratory infection at the Screening visit or the Baseline visit Any clinically significant cardiovascular disorder, renal, hepatic, gastrointestinal, or respiratory disease, including severe asthma History of, or current, cerebrovascular disease, brain trauma, epilepsy, or frequent migraines. A history of febrile seizures is not exclusionary Nasal surgery within 1 month of Screening visit or planning to have nasal surgery during the study. Unwilling to abstain from nasal saline, other nasal irrigation, and other intranasal medications during the Screening period and through the treatment period of the study Clinically significant irritability or agitation, requiring initiation of or increase in the dose of antipsychotic medication, within the 6 months prior to the Screening visit Used prostaglandins, prostaglandin analogues, or prostaglandin agonists in the 3 months prior to the Baseline visit. Inhibitors of prostaglandin synthesis, such as nonsteroidal anti-inflammatory drugs, are not exclusionary. Started a glucagon-like peptide 1 (GLP-1) agonist within the 6 months prior to the Screening visit. Treatment with GLP-1 agonist is allowed if the subject has been taking it for more than 6 months prior to Screening. Used oxytocin, desmopressin (DDAVP), or tesofensine within 6 months prior to the Baseline visit Active psychotic symptoms, a history of psychotic symptoms, or a psychotic disorder History of suicide attempt or inpatient psychiatric hospitalization New food-related interventions, including environment or dietary restrictions, within 1 month of the Screening visit Additional inclusion/exclusion criteria apply. Subjects will be evaluated at screening to ensure that all criteria for study participation are met.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carbetocin<br>Carbetocin nasal spray 3.2 mg three times daily (TID) | Drug: Carbetocin<br>* Carbetocin nasal spray 3.2 mg three times daily (TID)<br>* Other names: ACP-101;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo given TID, identical in appearance respective to carbetocin treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline at Week 12 in caregiver-rated Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score | The HQ-CT is a nine-item questionnaire designed to be completed by caregivers of subjects with PWS. It is a revision of the 11-item HPWSQ-R and has been further validated. The Foundation for Prader-Willi Research has made the HQ-CT available for clinical studies in PWS, and it is the consensus instrument within the PWS research community for measuring observable behaviors that stem from subjects' excessive drive to eat. The HQ-CT should be completed by the same caregiver throughout the study. The HQ-CT will be administered to the caregiver by a rater using standardized prompts. The Food Safe Zone should be administered immediately before administration of the HQ-CT. A higher score on the HQ-CT indicates greater severity of hyperphagia. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline at Week 12 in caregiver-rated Clinical Global Impression-Severity (CGI-S) score for PWS | The CGI-S is a rating scale that records a clinician's global impression of the current severity of illness on a seven-point scale, using a range of responses from 1 (normal) to 7 (among the most severely ill subjects). | Baseline to Week 12 | 
| Clinical Global Impression-Change (CGI-C) for PWS score at Week 12 | The CGI-C is a rating scale that records a clinician's global impression of change in severity of illness, using a range of responses from 1 (very much improved) to 7 (very much worse). | Score at Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized, Placebo-controlled