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 (<140/90 mmHg); may include stable dose (≥ 30 days of use) of up to two anti-hypertensive medications to achieve control and that are intended to remain on a stable dose during the protocol.
• Willingness (during screening) and demonstrated ability (as witnessed in the clinic prior to randomization) to self-administer study medication subcutaneously via a once or twice daily SC injection using a small insulin syringe.
• Willing to maintain a healthy diet and exercise regime throughout study as recommended by counseling at study start.
• Female participants must have negative serum pregnancy test and must not be lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method (i.e., sponge), or a double-barrier method of birth control (i.e., condom with spermicide) or abstinence must be used/ practiced throughout the study and for 90 days following the study.
• 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.
• 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 participants must not donate sperm for 90 days following their participation in the study.

Exclusion criteria

• Fasting blood glucose > 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 study or previously exposed to setmelanotide.
• History of alcohol or drug abuse within 5 years of Screening Visit.
• Any other reason, which in the opinion of the Investigator, would confound proper evaluation of the study.