A Phase 1 Study to Evaluate the Pharmacokinetics of Setmelanotide in Subjects With Varying Degrees of Renal Impairment
A Phase 1 Study to Evaluate the Pharmacokinetics of Setmelanotide in Subjects With Varying Degrees of Renal Impairment
This Phase 1, multi-center, study will enroll patients with renal insufficiency. Single
 ascending doses of setmelanotide will be evaluated, in semi-sequential group design. The
 following four cohorts of patients will be evaluated:

 Cohort A: setmelanotide in subjects with mild renal insufficiency Cohort B: setmelanotide in
 subjects with moderate renal insufficiency Cohort C: setmelanotide in subjects with severe
 renal insufficiency Cohort D: setmelanotide in subjects with normal renal function

 All subcutaneous doses will be administered to the abdominal region. Each dose will be
 studied in a separate cohort of subjects. Cohorts A and B will be performed in a parallel
 manner. After cohorts A and B have been studied and before subsequent cohort C is dosed, the
 available safety data (adverse events [AEs], clinical laboratory test results, vital signs
 and electrocardiograms) from the preceding cohort(s) will be reviewed. In addition, a 48h
 pause to evaluate safety will be implemented following the enrollment of the first 2 (two)
 patients in cohort C before treating the remaining patients in the cohort. Cohort D will be
 performed sequentially following cohort C. Depending on the safety data from the preceding
 cohort(s), a cohort may be repeated, or the dose may be reduced for future cohorts.
Inclusion Criteria:

 1. The subject is male or female 18 to 79 years of age, inclusive.

 2. The subject has a BMI of 22 to 35 kg/m2, inclusive, at screening.

 3. Female subjects of childbearing potential must use an acceptable method of birth
 control (ie, diaphragm with spermicide, intrauterine device, condom with foam or
 vaginal spermicide, oral contraceptives, or abstinence) or be surgically sterile (ie,
 hysterectomy, bilateral tubal ligation or bilateral oophorectomy), or postmenopausal
 (defined as amenorrhea 12 consecutive months and documented plasma
 follicle-stimulating hormone level in the postmenopausal range according to the
 laboratory used). Female subjects must have a negative pregnancy test at screening and
 before the first dose of study drug and must not be lactating. Male subjects with
 female partners of childbearing potential must be vasectomized, be willing to use an
 acceptable method of birth control, or practice abstinence during the study. Male
 subjects must not donate sperm during and for 90 days following their participation in
 the study.

 4. The subject agrees to comply with all protocol requirements.

 5. The subject is able to provide written informed consent.

 Additional Inclusion Criteria for Subjects with Renal Impairment Only (Cohorts A, B,
 and C):

 6. The subject has mild, moderate, or severe renal impairment as determined by eGFR and
 calculated using the MDRD formula.

 7. The subject's renal insufficiency or other related concomitant medical conditions (eg,
 hypertension, diabetes, anemia) have remained stable for at least 3 months before
 study drug dosing.

 8. The subject has a resting blood pressure of 90 to 165 mm Hg (systolic) and 45 to 100
 mm Hg (diastolic). Measurement can be repeated if the subject has an elevated value
 that is not consistent with previous history.

 9. The subject has a QTcF of <500 msec.

 10. The subject is judged by the investigator to be in good general health, as determined
 by medical history, clinical laboratory assessments, vital sign measurements, 12-lead
 ECG results, and physical examination findings, except for findings that, as judged by
 the investigator, are consistent with the subject's renal impairment or other stable
 concomitant medical conditions.

 Additional Inclusion Criteria for Healthy Subjects Only (Cohort D):

 11. The subject has normal renal function (≥90 mL/min) as determined by eGFR calculated
 using the MDRD formula.

 12. The subject will be "matched" to previous Cohorts A, B, and C with regards to age,
 sex, and BMI characteristics. Each subject in Cohort D will be within 20% of the
 median age and BMI of the combined median age and BMI across Cohorts A, B, and C.

 13. The subject has a resting blood pressure of 90 to 150 mm Hg (systolic) and 40 to 100
 mm Hg (diastolic).

 14. The subject is judged by the investigator to be in good general health, as determined
 by medical history, clinical laboratory assessments, vital sign measurements, 12-lead
 ECG results, and physical examination findings.

 Exclusion Criteria:

 1. The subject has a history or clinical manifestations of a significant neurological,
 cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, hepatic,
 genitourinary, endocrine, metabolic, or psychiatric disease that would preclude study
 participation, as judged by the investigator.

 2. The subject has a positive test result for human immunodeficiency virus Types 1 or 2
 antibodies or hepatitis B surface antigen at screening.

 3. The subject has a history of alcoholism or drug abuse within 3 months before
 screening.

 4. The subject is unable or unwilling to abstain from alcohol, marijuana and related
 substances, caffeine, cigarette smoking, vaping, or any form of tobacco or nicotine
 from 48 hours prior to study drug dosing until completing study assessments on Day 5.

 5. The subject is involved in strenuous activity or contact sports within 24 hours of the
 first dose of study drug or during the study.

 6. The subject has donated blood or blood products >450 mL within 30 days before the
 first dose of study drug.

 7. The subject has a history of relevant drug and/or food allergies (ie, allergy to
 setmelanotide or any excipients, or any significant food allergy).

 8. The subject has used prescription drugs from 1 week prior to randomization and
 throughout the study, except for prescription medications used for the treatment of
 stable concomitant conditions; examples include the following: diabetes, hypertension,
 hypercholesterolemia, hyperlipidemia or hypothyroidism. Medications used to treat
 these indications are allowed, so long as the subject has been on a stable dose for at
 least 2 weeks prior to randomization and plans to continue a stable dose throughout
 the study.

 9. The subject has received study drug in another investigational study within 30 days of
 dosing.

 10. The subject has a positive test result for drugs of abuse (including marijuana, and
 except positive test results associated with prescription medications that have been
 reviewed and approved by the investigator) or alcohol at screening or before the first
 dose of study drug.

 11. The subject has ALT or AST >2 × ULN at screening.

 12. The subject has HbA1c >10%.

 13. The subject has any personal history of cancer (unless stable and in remission for ≥5
 years), multiple atypical nevi, nevoid basal cell carcinoma syndrome, or nonmelanoma
 skin cancer requiring treatment beyond local excision.

 14. The subject has any close family history (parents or siblings) of melanoma.

 15. The subject has significant dermatologic findings relating to melanoma or premelanoma
 skin lesions, determined as part of a screening comprehensive skin evaluation
 performed by a qualified dermatologist. Any concerning lesions identified during
 screening will be biopsied and results known to be benign prior to enrollment. If the
 pretreatment biopsy results are of concern, the subject may need to be excluded from
 the study.

 16. The subject has history of clinically significant recent surgery (within 60 days of
 screening).

 17. The subject has current or recent (within last month) infection or viral illness.

 18. In the opinion of the investigator, the subject is not suitable for entry into the
 study.

 Additional Exclusion Criteria for Subjects with Renal Impairment Only (Cohorts A, B,
 and C):

 19. The subject has a positive test result for antibodies to hepatitis C virus with
 evidence of viral load at screening.

 20. The subject has nephrotic syndrome, defined as urine dipstick 4+ for protein and
 plasma albumin <3.0 g/dL, and then confirmed if proteinuria >5 g/day.

 21. The subject has renal impairment due to rapidly growing, space-occupying lesions (eg,
 carcinoma of the kidney, tuberculosis).

 22. Subject has a history of renal transplant.

 23. The subject has a hemoglobin value less than 8.5 g/dL.

 24. The subject has a clinically relevant immunologic disease.

 Additional Exclusion Criteria for Healthy Subjects Only (Cohort D):

 25. The subject has a positive test result for antibodies to hepatitis C virus at
 screening.