Prader-Willi Syndrome Clinical Trials

• Generally healthy male and female individuals between the ages of 13 and 50, inclusive

• Documented medical record history of PWS confirmed by genetic testing and PWS Nutritional Phase 3

• CGI-S score ≥4 at Screening and Baseline (behavioral)

• Screening HQ CT total scores ≥ 13

• Participants must not be taking SSRI, SNRI, DNRI (bupropion), tricyclic antidepressants, stimulants, antipsychotic medications, and MAO inhibitors within 30 days of screening and willing to not start taking these medications while on the study. Fluoxetine is exclusionary unless treatment has been discontinued \>6 months prior to Screening.

• Caregiver/parent must agree to bring the subject to the site for the visits, remain with the subject during visit times when allowed and respond to any questions.

• Caregiver/parent is willing to provide informed consent and agrees to adhere to required study procedures including telemedicine visits, visit duration requirements, and offer consistent care.

• Caregivers must agree to complete all study required assessments.

• Participants who cannot consent for themselves and are able will provide assent.

⁃ Female participants must not be pregnant or lactating. Nonpregnancy will be confirmed for all females by a urine pregnancy test conducted at Screening and at the Baseline Visit prior to enrollment into the study. If of childbearing potential, the subject/caregiver agrees to the use of one of the accepted contraceptive regimens from Screening to the first administration of the study medication, during the study, and for at least 30 days after the last dose of the study medication. An acceptable method of contraception includes one of the following:

∙ Hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)

‣ Intrauterine device (with or without hormones)

‣ OR agrees to use a double barrier method (e.g., condom and spermicide) during the study and for at least 30 days after the last dose of the study medication.

‣ The investigator can use their judgement and familiarity with the participant's preferred and usual lifestyle to understand which form of birth control would be the best and also to determine if abstinence is an option that would achieve 100% effectiveness.

⁃ If the female is of non-childbearing potential -surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is postmenopausal (at least 1 year without menses) as confirmed by follicle-stimulating hormone (FSH) levels of ≥ 40 mIU/mL. No contraceptive use is required.

⁃ Unless, sterile, a male study subject/caregiver must agree to use a double barrier method (e.g., condom and spermicide).

⁃ For adults, supine systolic blood pressure must be ≤140 mmHg and ≥100 mmHg; diastolic blood pressure must be ≤80 mmHg and ≥60 mmHg at Screening. Heart rate must be ≥50 bpm and ≤100 bpm. Heart rate increase on standing must be within acceptable range (see exclusion criterion 10).

⁃ For adolescents, a systolic and diastolic BP that is between the 5th and 90th percentile for age and sex.

⁃ a. Two repeat measurements within 10 minutes of the first reading are permitted at the discretion of the Investigator. If this option is used, the last obtained reading will be used for determination of eligibility. Averages will not be used.

⁃ All concomitant medications including blood pressure medications and type 2 diabetic medications must be stable for ≥3 months prior to screening (≤10% change) and there must be no medication changes (dose change, initiation, discontinuation) intentionally planned during the study. Supplements and vitamins are not considered concomitant medications for eligibility purposes.

⁃ Stated willingness to comply with all study procedures including visits, restrictions, and availability for the duration of the study.