A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Oral ARN-75039 in Healthy Adult Subjects

1. Is male or female, age 18 to 55 years, inclusive, at Screening.
2. Body mass index (BMI) between 18.5 and 35 kg/m2, inclusive, at Screening.
3. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Day -1 or 1.
4. Hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, and platelet count results within the laboratory reference range at Screening; subjects with Gilbert's disease with associated abnormalities of liver function tests are eligible for enrollment. Tests may be repeated at the discretion of the Investigator to confirm abnormalities.
5. Estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≥ 80 mL/min/1.73m2 at Screening
6. Females of childbearing potential must practice effective contraception per national regulatory guidelines for clinical trials from Screening, throughout the study and for 28 days after the EOS visit.
7. Females of childbearing potential must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug; for post-menopausal subjects, a blood sample will also be tested for follicle stimulating hormone (FSH) to confirm post-menopausal status (as verified by an FSH of ≥40). Surgically sterile females are eligible; however, proof via medical records will be required.
8. Males must agree to not donate sperm and/or to use condoms during sexual intercourse from the time of the first study drug administration and for 90 days following the last dose of study drug, and females must agree not to donate eggs from the time of the first study drug administration and for 60 days following the last dose of study drug.
9. Must be Willing and able to comply with measures to avoid photosensitivity reactions (i.e., avoidance of outdoor sun exposure and tanning; consistent use of long sleeve shirts, long pants, hats, and sunglasses; consistent use of SPF 75 or greater sunscreen when outdoors) from Day 1 through Day 8 in Part 1 and through Day 25 in Part 2.
10. Able to provide informed consent.
11. Willing and able to comply with this protocol and be available for the entire duration of the study.

Exclusion Criteria:

1. Any clinically significant underlying illness in the opinion of the Investigator.
2. Poor venous access.
3. Inability to ingest all capsules of a multi-capsule dose within 5 minutes of ingestion of the first capsule.
4. Prior exposure to ARN-75039.
5. Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) at Screening; subjects with adequately treated HCV are eligible for enrollment.
6. Positive test for SARS-CoV-2 infection on Day -1.
7. Consumption of Seville oranges, grapefruit or grapefruit juice within 72 hours prior to Day 1 or during the study.
8. History of drug or alcohol abuse within 1 year of Screening in the opinion of the investigator, or a positive test for drugs of abuse or alcohol at Screening or Day -1.
9. Use of any prescription or over-the-counter (OTC) medications, including food supplements, vitamins, herbal medications (e.g., St. John's wort), and cannabis, with the exception of contraceptive medications and as needed (prn) acetaminophen or paracetamol (not exceeding 2 grams/day) within 7 days prior to study drug administration and through the EOS visit.
10. History of malignancy, except adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix.
11. Smoking greater than 20 cigarettes, cigars, cigarillos or E-cigarettes per week in the 3 months prior to study drug administration or during the study.
12. Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and safety follow-up period.
13. Any reason or condition that, in the investigator's opinion, may compromise study participation, present a safety risk to the subject, or may confound the interpretation of the study results.
14. A QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450 millisecond (msec) based on either single or averaged QTcF values of triplicate ECGs obtained over a 3-minute interval (at Screening).
15. Blood product donation within 30 days before Screening.
16. unwilling to consume breakfast and dinner on study drug administration days

17. Currently enrolled in another investigational device or drug study, or less than 30 days or 5 half-lives of the prior investigational agent (whichever is longer) or plans to enroll in another investigational device or drug study during the course of this study.

    Part 2 (MAD) only:

18. History of:

    1. Structural abnormality of the gastrointestinal (GI) tract or a disease or history of a condition that can affect GI motility
    2. Inflammatory bowel disease (even if treated and currently in remission)
    3. Diverticulitis or any other chronic condition such as chronic pancreatitis, polycystic kidney disease, ovarian cysts, endometriosis, lactose intolerance that was associated with abdominal pain or discomfort and confounded the assessments in this trial.
    4. Chronic idiopathic diarrhea
    5. Formally diagnosed with colonic inertia or conditions that were associated with constipation: pseudo-obstruction, colonic inertia, megacolon, megarectum, bowel obstruction, descending perineum syndrome, solitary rectal ulcer syndrome, systemic sclerosis, lower tract evacuation disorders, functional outlet delay (e.g., rectal prolapse, anismus, etc.)
19. Current active peptic ulcer disease (i.e., disease that was not adequately treated or stable with therapy.)
20. Potential central nervous system cause of constipation (e.g., Parkinson's disease, spinal cord injury, and multiple sclerosis.)
21. Subject currently had both unexplained and clinically significant alarm symptoms (lower GI bleeding [rectal bleeding or heme-positive stool], iron-deficiency anemia or any unexplained anemia, or weight loss) or systemic signs of infection or colitis.
22. Subjects who did not expel at least 80% (19 or more) of the markers after the Sitzmarks® colonic transit test administered during the screening period.
23. History of chronic/generalized pruritus and/or severe skin rash of unknown origin
24. Subjects diagnosed with Type 1 or Type 2 diabetes, or with a blood glucose value >125 mg/dL during screening period.