Back to resultsA Study Examining Doses of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency
Primary Purpose
21-hydroxylase Deficiency
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Abiraterone acetate
Sponsored by
About this trial
This is an interventional treatment trial for 21-hydroxylase Deficiency focused on measuring 21-hydroxylase deficiency, Androstenedione, Abiraterone acetate, Pharmacokinetics, Pharmacodynamics, Dose-finding
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Abiraterone acetate
Arm Description
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.
Outcomes
Primary Outcome Measures
The minimum dose of abiraterone acetate required to decrease serum androstenedione to the age-appropriate range for adult women with 21-hydroxylase deficiency
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.
Secondary Outcome Measures
Mean serum concentrations of androstenedione
Mean serum concentrations of 17-hydroxyprogesterone
Mean plasma concentrations of renin activity
Mean serum concentrations of testosterone
Urine concentrations of androsterone
Urine concentrations of etiocholanolone
Maximum plasma concentration (Cmax) of abiraterone
Time to reach the maximum plasma concentration (tmax) of abiraterone
Area under the plasma concentration-time curve from time 0 to 24 hours postdose (AUC24) of abiraterone
Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of abiraterone
Time to last quantifiable plasma concentration (Tlast) of abiraterone
Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone
Full Information
NCT ID
NCT01495910
First Posted
November 23, 2011
Last Updated
February 27, 2014
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
1. Study Identification
Unique Protocol Identification Number
NCT01495910
Brief Title
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
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
21-hydroxylase Deficiency
Keywords
21-hydroxylase deficiency, Androstenedione, Abiraterone acetate, Pharmacokinetics, Pharmacodynamics, Dose-finding
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Abiraterone acetate
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Abiraterone acetate
Intervention Description
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.
Primary Outcome Measure Information:
Title
The minimum dose of abiraterone acetate required to decrease serum androstenedione to the age-appropriate range for adult women with 21-hydroxylase deficiency
Description
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.
Time Frame
Up to Day 7 of each treatment period.
Secondary Outcome Measure Information:
Title
Mean serum concentrations of androstenedione
Time Frame
Up to Day 8 of each treatment period.
Title
Mean serum concentrations of 17-hydroxyprogesterone
Time Frame
Up to Day 8 of each treatment period.
Title
Mean plasma concentrations of renin activity
Time Frame
Up to Day 8 of each treatment period.
Title
Mean serum concentrations of testosterone
Time Frame
Up to Day 8 of each treatment period.
Title
Urine concentrations of androsterone
Time Frame
Up to Day 8 of each treatment period.
Title
Urine concentrations of etiocholanolone
Time Frame
Up to Day 8 of each treatment period.
Title
Maximum plasma concentration (Cmax) of abiraterone
Time Frame
Up to Day 8 of each treatment period.
Title
Time to reach the maximum plasma concentration (tmax) of abiraterone
Time Frame
Up to Day 8 of each treatment period.
Title
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.
Title
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.
Title
Time to last quantifiable plasma concentration (Tlast) of abiraterone
Time Frame
Up to Day 8 of each treatment period.
Title
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.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
Facility Information:
City
Chicago
State/Province
Illinois
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Dallas
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=2559&filename=CR100007_CSR.pdf
Description
An Open-Label, Multiple-Dose, Dose-Finding Study of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency
Learn more about this trial
A Study Examining Doses of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency
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