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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open-Label, Multiple-Dose, Dose-Finding Study of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Current Primary Outcome: The minimum dose of abiraterone acetate required to decrease serum androstenedione to the age-appropriate range for adult women with 21-hydroxylase deficiency [ Time Frame: Up to Day 7 of each treatment period. ]

Normalization or reduction of age-appropriate androstenedione levels will be determined by the mean of the androstenedione values measured on Study Days 6 and 7 of the treatment period.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mean serum concentrations of androstenedione [ Time Frame: Up to Day 8 of each treatment period. ]
  • Mean serum concentrations of 17-hydroxyprogesterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Mean plasma concentrations of renin activity [ Time Frame: Up to Day 8 of each treatment period. ]
  • Mean serum concentrations of testosterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Urine concentrations of androsterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Urine concentrations of etiocholanolone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Maximum plasma concentration (Cmax) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Time to reach the maximum plasma concentration (tmax) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • 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. ]
  • 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. ]
  • Time to last quantifiable plasma concentration (Tlast) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • 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. ]


Original Secondary Outcome:

  • Mean serum concentrations of androstenedione [ Time Frame: Up to Day 8 of each treatment period. ]
  • Mean serum concentrations of 17-hydoxyprogesterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Mean plasma concentrations of renin activity [ Time Frame: Up to Day 8 of each treatment period. ]
  • Mean serum concentrations of testosterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Urine concentrations of androsterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Urine concentrations of etiocholanolone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Maximum plasma concentration (Cmax) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • Time to reach the maximum plasma concentration (tmax) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • 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. ]
  • 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. ]
  • Time to last quantifiable plasma concentration (Tlast) of abiraterone [ Time Frame: Up to Day 8 of each treatment period. ]
  • 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. ]


Information By: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Dates:
Date Received: November 23, 2011
Date Started: December 2011
Date Completion:
Last Updated: February 27, 2014
Last Verified: February 2014