Phase 1b/2a Study to Evaluate Safety and Efficacy of Setmelanotide in Obese Patients

Inclusion Criteria

• Be between the ages of 18 and 65 years, inclusive.
• Able to provide voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures.
• In good general health, without significant medical history, physical examination findings, or clinical laboratory abnormalities.
• Body Mass Index: 30 to 40 Kg/m2.
• Stable body weight by participant report (+/- 5 Kg) during previous 6 months.
• Blood pressure ( than 140 mg/dL.
• TSH level outside the normal range.
• Creatinine > 1.5 times the upper limit of normal.
• Liver function tests > 2 times the upper limit of normal.
• Active or history of any significant medical condition including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease.
• Patients with a history of the following:
• Uncontrolled hypertension;
• Diabetes requiring medical treatment;
• Major depressive disorder within the last 2 years;
• Any lifetime history of a suicide attempt;
• Any suicidal ideation/behavior in the last month;
• Other severe psychiatric disorders (e.g. schizophrenia, bipolar disorder, severe eating disorders including bulimia).
• A PHQ-9 score of ≥15.
• Any suicidal ideation of type 4 or 5 on the C-SSRS.
• Prior bariatric surgery.
• History or close family history (parents or siblings) of melanoma.
• Significant dermatologic findings as part of the Screening comprehensive skin evaluation performed by the dermatologist.
• Currently treated with anorectic agents or drugs in last 2 months from screening with anorexia as a frequent side event.
• Taking more than 2 anti-hypertensive medications.
• Acute illness or history of illness, which in the opinion of the Investigator, could pose a threat or harm to the patient or obscure interpretation of laboratory test results or interpretation of study data.
• History of any malignancy, past or present, including skin cancer, multiple severely dysplastic nevi, or nevoid basal cell carcinoma.
• History of HIV infection or Hepatitis B or C.
• History of significant drug hypersensitivity or anaphylaxis.
• History of hypersensitivity to proteins (e.g., allergy shots).
• Any clinically significant abnormalities on screening laboratories as determined by the Investigator.
• Abnormal 12-lead electrocardiogram (ECG) at screening, except minor deviations deemed to be of no clinical significance by the Investigator. QTcF must be < 450 ms.
• Received any experimental drugs or devices or have participated in a clinical study within 30 days prior to dosing.
• Blood donation greater than 500 mL within 60 days prior to screening or intent to donate up to 30 days after Final Study Visit.
• Hospitalization for surgery within the 3 months prior to screening except for minor outpatient procedures, or any planned hospitalizations during the study period.
• Poor venous access or inability to tolerate venipuncture.
• Inability to attend all study visits or comply with protocol requirements including fasting and restrictions on concomitant medication intake.
• Participation in weight loss programs during the study period, including nutritional supplements/ replacements other than as recommended by nutritional counseling provided at study start.
• Use of prescription medications on a regular basis with the following exceptions:
• Contraceptives (must be on for ≥3 months);
• Hormone replacement therapy (must be on stable dose for ≥3 months);
• Antihypertensives (<2 medications on a stable dose for ≥ 30 days);
• Statins (dose must be ≤ half the maximum dose; must be on a stable dose ≥3 months);
• Thyroxin (stable dose for ≥ 30 days);
• The last use of any other prescription medication must have been greater than 5 half-lives for the specific medication or at least 14 days prior to randomization, whichever is longer.
• Women who are pregnant or are breast feeding.
• Previously randomized and dosed in this stu