Clinical trial NCT01495910: A Study Examining Doses of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency
Official title: An Open-Label, Multiple-Dose, Dose-Finding Study of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 21-hydroxylase Deficiency
Keywords: 21-hydroxylase deficiency
Androstenedione
Abiraterone acetate
Pharmacokinetics
Pharmacodynamics
Dose-finding
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2011-12-20
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The minimum dose of abiraterone acetate required to decrease serum androstenedione to the age-appropriate range for adult women with 21-hydroxylase deficiency
timeFrame: Up to Day 7 of each treatment period.
Secondary outcomes:
measure: Mean serum concentrations of androstenedione
timeFrame: Up to Day 8 of each treatment period.
measure: Mean serum concentrations of 17-hydroxyprogesterone
timeFrame: Up to Day 8 of each treatment period.
measure: Mean plasma concentrations of renin activity
timeFrame: Up to Day 8 of each treatment period.
measure: Mean serum concentrations of testosterone
timeFrame: Up to Day 8 of each treatment period.
measure: Urine concentrations of androsterone
timeFrame: Up to Day 8 of each treatment period.
measure: Urine concentrations of etiocholanolone
timeFrame: Up to Day 8 of each treatment period.
measure: Maximum plasma concentration (Cmax) of abiraterone
timeFrame: Up to Day 8 of each treatment period.
measure: Time to reach the maximum plasma concentration (tmax) of abiraterone
timeFrame: Up to Day 8 of each treatment period.
measure: Area under the plasma concentration-time curve from time 0 to 24 hours postdose (AUC24) of abiraterone
timeFrame: Up to Day 8 of each treatment period.
measure: Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of abiraterone
timeFrame: Up to Day 8 of each treatment period.
measure: Time to last quantifiable plasma concentration (Tlast) of abiraterone
timeFrame: Up to Day 8 of each treatment period.
measure: Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone
timeFrame: Up to Day 8 of each treatment period.
Other outcomes:
Locations:
city: Chicago
country: United States
state: Illinois
city: Ann Arbor
country: United States
state: Michigan
city: Dallas
country: United States
state: Texas
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Clinical Trial
role: STUDY_DIRECTOR
References: