Androgen Reduction in Congenital Adrenal Hyperplasia, Phase 1

Exclusion Criteria

• •1. Evidence of central puberty: Tanner Stage \>2 for breast development in girls or testicular volume \>4 mL in boys, or random luteinizing hormone (LH) \>0.3 milli-international units (mIU)/mL. Subjects with pubic and/or axillary hair as the only sign of puberty onset will be allowed.
• •2. Current or history of hepatitis from any etiology, including history of active viral hepatitis A, B, or C.
• •3. Patients with baseline hepatic impairment are excluded from this trial. To be eligible for this protocol, patients must meet all of the following criteria:
• •AST, ALT and Total bilirubin \< ULN Albumin \> lower limits of normal (LLN) No evidence of ascites No evidence of encephalopathy
• •4. Abnormalities of liver function developing during the study
• •5. Abnormal renal function tests, defined as blood urea nitrogen (BUN) or creatinine \>1.5 ULN for age.
• •6. Significant anemia (hemoglobin \< 12 g/dl). If documented to be due to iron deficiency, subjects may be rescreened 3 months after this has been treated.
• •7. Clinically significant abnormality in the 12-lead electrocardiogram (ECG)
• •8. A history of a malabsorption syndrome.
• •9. Evidence of active malignancy.
• •10. Serious or uncontrolled co-existent disease, including active or uncontrolled infection. Subjects may be rescreened after resolution of any such condition.
• •11. Concurrent medical condition or disease other than 21-hydroxylase deficiency that may interfere with linear growth or that requires concomitant therapy that is likely to interfere with study procedures or results.
• •12. Asthma or other condition requiring treatment with systemic corticosteroids within the past 3 months. Asthma treatment with inhaled corticosteroids is permitted.
• •13. Treatment with potentially hepatotoxic medications (statins); strong inhibitors of CYP3A4 (ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), or CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). CYP2C8 substrates (rosiglitazone, pioglitazone, rapaglinide) and CYP2D6 substrates (dextromethorphan, thioridazine) should be avoided
• •14. Treatment with medications to affect puberty or synthesis of sex steroids, including gonadotropin releasing hormone agonists, aromatase inhibitors, or androgen receptor blockers (e.g., flutamide, spironolactone). However, a gonadotropin releasing hormone agonist may be started during the study for treatment-emergent central puberty without disqualifying the subject
• •15. Treatment with growth hormone at enrollment or during the course of the study.
• •16. Known allergies, hypersensitivity, or intolerance to abiraterone acetate or its excipients (refer to United States Prescribing Information).
• •17. Has received an investigational drug within 4 weeks of the planned first dose of study drug or is currently enrolled in an investigational interventional study.
• •18. Any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments.
• •19. Presence or history of cataracts.