A Study Examining Doses of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency

• Mean serum concentrations of androstenedione [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Mean serum concentrations of 17-hydroxyprogesterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Mean plasma concentrations of renin activity [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Mean serum concentrations of testosterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Urine concentrations of androsterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Urine concentrations of etiocholanolone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Maximum plasma concentration (Cmax) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Time to reach the maximum plasma concentration (tmax) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Area under the plasma concentration-time curve from time 0 to 24 hours postdose (AUC24) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Time to last quantifiable plasma concentration (Tlast) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]

• Mean serum concentrations of androstenedione [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Mean serum concentrations of 17-hydoxyprogesterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Mean plasma concentrations of renin activity [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Mean serum concentrations of testosterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Urine concentrations of androsterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Urine concentrations of etiocholanolone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Maximum plasma concentration (Cmax) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Time to reach the maximum plasma concentration (tmax) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Area under the plasma concentration-time curve from time 0 to 24 hours postdose (AUC24) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Time to last quantifiable plasma concentration (Tlast) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]
• Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ] [ Designated as safety issue: No ]

The purpose of this study is to determine the minimum dose of abiraterone acetate needed to decrease serum androstenedione to age-appropriate levels in premenopausal women on steroid replacement for classic 21-hydroxylase deficiency.

This is a non-randomized (patients will not be assigned by chance to study treatments), open-label (patients will know the identity of study treatments), multiple-dose, intra-patient sequential dose-escalation study with a planned enrollment of approximately 10 patients. This study will consist of a screening period and a treatment period. Due to the intra-patient dose escalation, there will be multiple treatment periods consisting of 8 days each. A rest period of at least 7 days will separate each treatment period. Eligible patients will take study-defined replacement doses of hydrocortisone and fludrocortisone. Abiraterone acetate oral suspension will be administered in daily escalating doses from 100 mg to 500 mg. Patients will proceed to the next higher dose level when the majority of the treated patients have a reduction in the androstenedione level. Serial pharmacokinetic (study of what the body does to a drug) and pharmacodynamic (study of the effects of a drug on the body) samples will be collected at each treatment period as detailed in the protocol. All patients who receive at least 1 dose of abiraterone acetate will be analyzed for safety.

Inclusion Criteria:

• Premenopausal women >=18 years of age.
• Must be receiving a hormonal contraceptive agent containing both estrogen and progesterone.
• Confirmed 21-hydroxylase deficiency by CYP21A2 genotype associated with classic congenital adrenal hyperplasia.
• Demonstrates a >=1.5 X ULN of morning serum androstenedione concentration while taking study-defined doses of hydrocortisone and fludrocortisone.
• No coexisting medical conditions in the opinion of the investigator that would preclude participation in the study.

Exclusion Criteria:

• Current or history of active or chronic hepatitis, including symptomatic viral hepatitis A, B, or C.
• Any active infection.
• Evidence of active malignancy.
• Serious or uncontrolled co-existent non-malignant disease.
• Receiving systemic glucocorticoids for any reason other than for the treatment of 21-hydroxylase deficiency.
• Any disorders that require treatment with anticonvulsants.
• Patients of child-bearing potential who are not willing to use a method of birth control during the study and for 3 months after the end-of-study.
• Women who are pregnant or breast-feeding.
• Genotypes associated with non-classic congenital adrenal hyperplasia.