['prader-willi syndrome']
['rm-493', 'placebo']

        Inclusion Criteria:

          1. PWS due to chromosome 15 micro-deletion, maternal uniparental disomy, or imprinting
             defect, confirmed by fluorescent in situ hybridization, chromosomal microarray, and/or
             methylation studies. Obese male or female volunteers weighing at least 50 kg with BMI
             ≥27 kg/m²

          2. Age 16-65 years

          3. If a volunteer has diagnosis of type 2 diabetes, following criteria must be met:

               1. HbA1c <7.5% not being managed with insulin. Patients taking GLP-1 analogues
                  (exenatide or liraglutide) must have been on stable dose for greater than 3
                  months.

               2. Fasting plasma glucose <140 mg/dL

               3. No history of ketoacidosis or hyperosmolar coma

          4. Vital signs must be within the following ranges and stable.

               1. Systolic blood pressure, 90-150 mm Hg

               2. Diastolic blood pressure, 50-90 mm Hg

               3. Pulse rate, 40-100 bpm

          5. Stable body weight at home for ~2 months (self or guardian-reported loss/gain within ±
             5%).

          6. Blood pressure (≤150/90 mmHg); may include stable dose (≥ 30 days of use) of up to two
             anti-hypertensive medications that are intended to remain on a stable dose during the
             protocol

          7. Parent or guardian is able to communicate well with the investigator, to understand
             and comply with the requirements of the study, and be able to understand and sign the
             written informed consent. Due to the significant intellectual disability with PWS,
             assent is to be provided by the patient who cannot consent for himself or herself.

          8. Results of screening clinical laboratory tests (CBC with differential and platelets
             and chemistry profile) must be within normal range or, if outside of the normal range,
             must be accepted by the investigator and sponsor as not clinically significant.

          9. Females of non-childbearing potential, defined as surgically sterile (status post
             hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal
             for at least 12 months (and confirmed with a screening FSH level in the
             post-menopausal lab range), do not require contraception during the study. All other
             females of child-bearing potential must agree to use contraception as outlined in the
             protocol.

         10. Males with female partners of childbearing potential must agree to a double barrier
             method if they become sexually active during the study and for 90 days following the
             study. Male subjects must not donate sperm for 90 days following their participation
             in the study.

         11. Patients must be on a stable dose of any allowed chronic concomitant medications while
             participating in the study, as described in protocol. This is defined as no changes in
             medication for at least 60 days prior to Day 1 and no changes in dose for at least 30
             days prior to Day 1; Note that stable concomitant usage (>3 months) of growth hormone,
             hormone replacement therapy, GLP-1 agents, statins, or other medications (excluding
             insulin, modafinil, anti-psychotics), and other medications commonly used in PWS
             patients are allowed (See Section 6.4.5 on Concomitant medications).

        Exclusion Criteria:

          1. Recent use (within 3 month) of weight loss agents including herbal medication.

          2. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other DSM-III
             disorders which the investigator believes will interfere significantly with study
             compliance.

          3. A PHQ-9 score of ≥15.

          4. Any suicidal ideation of type 4 or 5 on the C-SSRS.

          5. Clinically significant illness in the 8 weeks before screening.

          6. History of clinically significant bleeding disorders.

          7. Current, clinically significant liver, renal, pulmonary, cardiac, oncologic, or GI
             disease.

          8. Diagnosis of type 1 diabetes mellitus or other active endocrine disorders (e.g.,
             Cushing syndrome, or thyroid dysfunction except if on adequate thyroid or
             glucocorticoid replacement supplement).

          9. Cardiovascular disease event including history of CHF, coronary artery disease, MI,
             second degree or greater heart block or prolonged QT syndrome.

         10. Blood pressure >150/90 mmHG.

         11. Liver disease or liver injury as indicated by abnormal liver function tests, SGOT
             (AST), alkaline phosphatase, or serum bilirubin (> 1.5 x ULN for any of these tests)
             or history of hepatic cirrhosis.

         12. History or presence of impaired renal function as indicated by clinically
             significantly abnormal creatinine, BUN, or urinary constituents (e.g., albuminuria) or
             moderate to severe renal dysfunction as defined by the Cockroft Gault equation (< 50
             mL/min).

         13. History or close family history (parents or siblings) of melanoma.

         14. Oculocutaneous albinism (occurs at ~1% in PWS).

         15. Significant dermatologic findings as part of the Screening comprehensive skin
             evaluation performed by the dermatologist. Any concerning lesions identified during
             the screening period will be biopsied and results known to be benign prior to
             randomization. If the pre-treatment biopsy results are of concern, the patient will be
             excluded from the study.

         16. Significant history of abuse of drugs or solvents in the year before screening or a
             positive Drugs of Abuse (DOA) test at screening.

         17. History of alcohol abuse in the past year before screening or currently drinks in
             excess of 21 units per week (3 servings or units/day).

         18. Caffeine consumption exceeding 6 cups of caffeinated tea/coffee (or equivalent) per
             day.

         19. Volunteer is, in the opinion of the Investigator, not suitable to participate in the
             study.

         20. Participation in any clinical study with an investigational drug/device within 3
             months prior to the first day of dosing.

         21. Positive history for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
             tests or tuberculosis.

         22. Serious adverse reaction or significant hypersensitivity to any drug.

         23. Clinically significant blood loss or blood donation > 500 mL within 3 month.

         24. Inadequate venous access.

         25. History of low blood counts or recurring infections.
      