A Study of CSTI-500 in Patients With Prader-Willi Syndrome

Exclusion Criteria

• •1. Participation in any clinical study with an investigational drug/device within 3 months prior to screening or during the study
• •2. PWS diagnosis of UPD (maternal uniparental disomy).
• •3. Current use of DCCR or if used previously, must be off at least 4 weeks before screening.
• •4. Recent use (within 3 months) of weight loss agents including prescription, herbal medications, and weight loss supplements. Ozempic, for diabetes, would be exclusionary due to its effect on weight loss.
• •5. History of bariatric surgery or major surgery within 6 months of screening or planned during the study.
• •6. Any malignancy in the 2 years prior to screening (excluding basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated).
• •7. Current liver, pulmonary, cardiac, or GI disease that would be expected to adversely affect study participation. Stable disease, e.g., asthma or controlled hypertension is not excluded. Liver disease or liver injury as indicated by abnormal liver function tests, ALT, AST, alkaline phosphatase, or serum bilirubin (≥3X ULN for any of these tests).
• •a. Participants with impaired liver function (Child-Pugh Scores A, B, C)
• •8. Unexplained history or presence of combination of unexplained symptoms e.g., dizziness, syncope, fatigue, palpitations/tachycardia, headaches, or exercise intolerance.
• •9. Prohibited Medications include SSRI, SNRI, DNRI (bupropion), tricyclic antidepressants, stimulants, antipsychotics, MAO inhibitors, fluoxetine, mood stabilizers, and GLP-1 agonists
• •10. Presence of postural orthostatic tachycardia syndrome (POTS) for any reason, defined as:
• •1. For participants aged 19 or older, sustained heart rate increase of \>30 bpm or an increase to 120 bpm or greater within 3 minutes of standing.
• •2. For participants aged 13-19, a sustained heart rate increase of \>40 bpm or an increase to 120 bpm or greater within 3 minutes of standing.
• •3. Associated with related symptoms that are worse with upright posture and that improve with recumbence.
• •11. A clinically significant abnormal finding on 12-lead electrocardiogram (ECG) at Screening. Note QT corrected according to Fridericia's formula (QTcF) interval of ≥450 msec will be exclusionary \[QTc = QT/(RR\^0.33)\]. The ECG may be repeated once for confirmatory purposes if initial values obtained exceed the limits specified.
• •12. Any clinically significant cardiac arrhythmia (e.g., atrial fibrillation, Adams-Stokes's disease, Wolff-Parkinson-White syndrome, atrioventricular block 2nd or 3rd degree).
• •13. Heart failure classified per the New York Heart Association (NYHA) as level II or greater.
• •14. Myocardial infarction, stroke, or confirmed TIA within the last 5 years.
• •15. Estimated glomerular filtration rate (eGFR) ≤ 90 mL/min/1.73m² for ages 13 to \<18 years of age. For adults ≥18 years of age, body-surface area corrected eGFR and exclusion with eGFR \<90 mL/min.
• •16. Uncontrolled Type 2 diabetes as defined by HbA1c ≥ 9% at Screening.
• •17. Insulin-dependent Type 1 diabetes.
• •18. Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies with detected circulating ribonucleic acid (RNA), or HIV 1 and 2 antibodies.
• •19. Uncontrolled thyroid disease.
• •20. Known hypersensitivity to any component of investigational product.
• •21. History or active psychotic symptoms, or medical conditions which the investigator believes will interfere significantly with study compliance. Participants with a history of other severe psychiatric disorders, e.g., schizophrenia, major depressive disorder, bipolar disorder, or other DSM-V disorders.
• •22. History of any suicidal behavior.
• •23. Known alcohol or substance abuse.
• •24. Moderate to strong inhibitors/inducers of CYP2D6, CYP3A4 and CYP2C9, including grapefruit juice. Substrates of CYP1A2 and CYP2B6.
• •25. Any other medical, physical, or personal issues which, in the opinion of the investigator, would interfere with the subject's ability to complete the trial per protocol.
• •26. Inability to swallow the oral capsules whole with water.