Inclusion Criteria

• Must meet all of the following
  • Provides signed and dated informed consent prior to any study-specific procedures
  • Male or female
  • Age 18-80 years (inclusive) at screening
  • Must have a confirmed diagnosis of endogenous Cushing’s syndrome as evidenced by
    • Baseline UFC 1.3 to 10 × ULN (mean of all 24-hr UFC levels obtained during the screening period within 14 days of enrollment) 
    • Documentation at any time of ONE of the following criteria
      • For a diagnosis of pituitary Cushing’s syndrome, Magnetic resonance imaging (MRI) confirmation of pituitary adenoma (greater than or equal to 0.6 cm)
      • For a pituitary microadenoma less than 0.6 cm, bilateral inferior petrosal sinus sampling (BIPSS) showing an ACTH gradient > 2 before or > 3 after corticotropin-releasing hormone (CRH) or desmopressin (DDAVP) stimulation
      • For prior pituitary surgery: histopathology confirming an ACTH-staining adenoma
      • For a diagnosis of adrenal Cushing’s syndrome: MRI or computed tomography (CT) of the adrenal glands showing an adrenal tumor
      • For a diagnosis of ectopic ACTH as the cause of their Cushing’s syndrome: ACTH- dependent Cushing’s syndrome and
    • MRI showing no pituitary adenoma
    • MRI showing only a small pituitary adenoma (< 0.6 cm) AND a negative BIPSS
      • For prior pituitary surgery: histopathology that is negative for an ACTH- staining adenoma
• Prior pituitary surgery must be at least 6 months post-surgery at the time of the screening visit
• Body mass index (BMI) between 18 and 45 kg/m2, inclusive, at screening
• Female subject must be
  • Postmenopausal > 2 years
  • Permanently surgically sterilized (bilateral salpingectomy or tubal occlusion) > 2 years 
  • With male partner(s) who has had a vasectomy > 2 years 
  • Consenting to use two permitted medically-acceptable methods of contraception throughout the study during any sexual intercourse with a male partner
    • Permitted medically-acceptable methods of birth control for this study are defined as use of a male condom plus one of the following: spermicide, diaphragm with spermicide, contraceptive sponge, or an intrauterine device

Exclusion Criteria

• Meet any of the following
  • Pseudo-Cushing’s syndrome, cyclic Cushing’s syndrome or current iatrogenic Cushing’s syndrome
  • Considered candidate for surgical treatment of Cushing’s syndrome, unless there is a clearly documented refusal of such surgery or that surgery cannot be scheduled for at least the anticipated duration of the study
  • Normal late night salivary cortisol value during screening ( would be suggestive of pseudo-Cushing’s or cyclic Cushing’s)
  • Normal 24-hr UFC during screening (this would be suggestive of cyclic Cushing’s)
  • Radiotherapy of the pituitary within 1 year prior to or during screening
  • For pituitary Cushing’s syndrome, any compression of the optic chiasm or the presence of a tumor within 2 mm of the optic chiasm on the most recent pituitary MRI prior to or during screening
  • Use of or medical requirement for any of the following medications within the timeframes specified below prior to day14 and throughout study participation
    • Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week
    • Pituitary-directed agents: Dopamine agonists (bromocriptine, cabergoline) and PPARγ agonists(rosiglitazone or pioglitazone): 4 weeks
    • Octreotide LAR, Lanreotide SR and Lanreotide autogel: 14 weeks
    • Octreotide (immediate release formulation): 1 week
    • Pasireotide: 4 weeks
    • Mitotane: 26 weeks
    • Mifepristone: 3 weeks
  • Uncontrolled diabetes mellitus, as evidenced by HbA1c > 9.0% at screening
  • Uncontrolled hypertension, defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 90 mmHg during screening
    • If appropriate, blood pressure medications may be adjusted and blood pressure reassessed at an unscheduled visit prior to visit T1
  • Any history of gastric or small intestinal surgery or any current disease that causes malabsorption
    • Irritable bowel syndrome is acceptable for inclusion
  • Alcohol or substance abuse (cocaine, amphetamines and/or opioids) within the year prior to screening
  • Abnormal laboratory values as per the guidelines listed below or any other clinically significant, unexplained laboratory abnormality according to the Investigator
    • Serum ALT or AST > 3 × ULN
    • Serum total bilirubin > 1.5 × ULN
    • Serum creatinine > 1.5 × ULN
    • Creatinine clearance < 60 mL/min
  • Pregnant, breast-feeding, has conceived within the 6 months prior to screening, or intends to become pregnant during the study period
  • QTc > 470 msec on electrocardiogram at screening 
    • A single QTc > 470 msec may have 2 additional ECGs taken during screening and averaged
    • If the average QTc is > 470 msec then the subject is excluded
  • Known history of Gilbert’s syndrome
  • HIV, hepatitis B, or hepatitis C positivity at screening
  • Any malignancy within the previous 10 years, other than curatively resected basal or squamous cell skin cancer
  • Previous exposure to any amount of ATR-101
  • Participation in any study of an investigational drug within 30 days prior to screening
  • Significant psychiatric disease, recent severe physical stress, malnutrition, chronic excessive exercise, or any other medical or psychiatric condition that, in the opinion of the Investigator, is likely to confound the interpretation of the study results or prevent the subject from understanding the requirements of or successfully completing the study