A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH

Exclusion Criteria

• •1. Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21 hydroxylase deficiency)
• •2. Has a history that includes bilateral adrenalectomy or hypopituitarism
• •3. Has a history of allergy or hypersensitivity to tildacerfont, any of its excipients, or any other CRF1 receptor antagonist
• •4. Current treatment with dexamethasone as GC therapy for CAH
• •a. Prior treatment with dexamethasone is allowed as long as the transition to an alternative GC regimen (eg, HC, prednisone, or prednisolone) has resulted in a stable dose of GC replacement for ≥1 month before screening.
• •5. Is not adherent to GC or study drug dosing regimen during the Run-in Period (defined as taking \<80% of expected doses based on drug accountability)
• •6. Shows clinical signs or symptoms of adrenal insufficiency
• •7. Has had a clinically significant unstable medical condition, medically significant illness, or chronic disease occurring within 30 days of screening, including but not limited to:
• •1. An ongoing malignancy or \<3 years of remission history from any malignancy, other than successfully treated localized skin cancer
• •2. eGFR of \<45 mL/min/1.73 m2
• •3. Current or history of liver disease (with the exception of Gilbert's syndrome).
• •4. History of alcohol or substance abuse within the last year, or any significant history of alcohol or substance abuse that would likely prevent the subject from reliably participating in the study, based on the opinion of the Investigator
• •5. Active hepatitis B, hepatitis C, or HIV at screening
• •6. Subjects who plan to undergo bariatric surgery during the study are excluded.
• •7. Any other condition that would impact subject safety or confound interpretation of study results
• •8. Psychiatric conditions, including but not limited to bipolar disorder, schizophrenia, or schizoaffective disorders that are not effectively controlled on medication and may have an adverse impact on study compliance. Symptoms including hallucinations, delusions, and psychosis are exclusionary. Additionally:
• •1. Increased risk of suicide based on the Investigator's judgment or the results of the C-SSRS conducted at screening and Week 6 (eg, C-SSRS Type 3, 4, or 5 ideation within the past 6 months or any suicidal behavior within the past 12 months)
• •2. HADS score \>12 for either depression or anxiety at screening or Week 6
• •9. Has clinically significant abnormal ECG or clinical laboratory results. Abnormal results that must be reviewed and discussed with the Medical Monitor to determine eligibility for this study include but are not limited to:
• •1. Any clinically meaningful abnormal ECG results, including QTcF \>450 ms for male participants or \>470 ms for female participants
• •2. ALT \>2x ULN
• •3. Total bilirubin \>1.5x ULN
• •4. Total bile acids \>5x ULN
• •10. Routinely works overnight shifts
• •11. Subjects with travel plans/work schedules that result in significant and frequent changes in time zones (\>2 hours) will require Medical Monitor approval for enrollment.
• •12. Females who are pregnant or nursing
• •13. Use of any other investigational drug from 30 days or 5 half-lives (whichever is longer) before screening to the end of the study
• •14. Use of the following drugs from 30 days or 5 half-lives (whichever is longer) before Day 1 to the end of the study:
• •1. Rosiglitazone, aromatase inhibitors, testosterone, growth hormones, or any other medication or supplement that could impact subject safety or confound interpretation of study results
• •2. The following drugs:
• •i. Moderate to strong inhibitors and/or inducers of CYP3A4 ii. Sensitive substrates or narrow-therapeutic-range substrates of CYP3A4 (except hormonal contraception containing ≤35 μg ethinyl estradiol) iii. Sensitive substrates or narrow-therapeutic-range substrates of BCRP (except those that can be administered QD in the morning, separated by approximately 10 hours from evening administration of study drug)
• •15. Donation or receipt of blood from 90 days before Screening to the end of the study; donation or receipt of platelets, white blood cells, or plasma from 30 days before Screening to the end of the study