| Eligibility |
Inclusion Criteria:
1. The subject is male or female 18 to 83 years of age, inclusive.
2. The subject has a BMI of 22 to 40 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%. With Sponsor approval, a subject who has a HbA1c >10% may
be enrolled into the study if, in the opinion of the primary investigator, the
subject's diabetes is reasonably controlled and the subject is otherwise appropriate
for this study.
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, the principle investigator, or a nurse
practitioner (ordered by preference) . 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 8.0 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.
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