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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01495910
First received: November 23, 2011
Last updated: February 27, 2014
Last verified: February 2014

November 23, 2011
February 27, 2014
December 2011
February 2013   (final data collection date for primary outcome measure)
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. ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01495910 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
 
A Study Examining Doses of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency
An Open-Label, Multiple-Dose, Dose-Finding Study of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency

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.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
21-hydroxylase Deficiency
Drug: Abiraterone acetate
Abiraterone acetate oral suspension administered daily from study Day 1 to study Day 6 of each treatment period: the first dose level is 100 mg with escalating doses of 250 mg and 500 mg in subsequent treatment periods.
Experimental: Abiraterone acetate
Abiraterone acetate oral suspension administered daily from study Day 1 to study Day 6 of each treatment period: the first dose level is 100 mg with escalating doses of 250 mg and 500 mg in subsequent treatment periods.
Intervention: Drug: Abiraterone acetate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
6
February 2013
February 2013   (final data collection date for primary outcome measure)

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.
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01495910
CR100007, 212082HPL1002
Yes
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Not Provided
Study Director: Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP