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

21-hydroxylase Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01495910
• Other study ID #: CR100007
• Secondary ID: 212082HPL1002
• Status: Completed
• Phase: Phase 1
• First received: November 23, 2011
• Last updated: February 27, 2014
• Start date: December 2011
• Est. completion date: February 2013

Study information

• Verified date: February 2014
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 21-hydroxylase Deficiency
• Adrenal Hyperplasia, Congenital
• Adrenogenital Syndrome

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to Day 7 of each treatment period.	No
Secondary	Mean serum concentrations of androstenedione		Up to Day 8 of each treatment period.	No
Secondary	Mean serum concentrations of 17-hydroxyprogesterone		Up to Day 8 of each treatment period.	No
Secondary	Mean plasma concentrations of renin activity		Up to Day 8 of each treatment period.	No
Secondary	Mean serum concentrations of testosterone		Up to Day 8 of each treatment period.	No
Secondary	Urine concentrations of androsterone		Up to Day 8 of each treatment period.	No
Secondary	Urine concentrations of etiocholanolone		Up to Day 8 of each treatment period.	No
Secondary	Maximum plasma concentration (Cmax) of abiraterone		Up to Day 8 of each treatment period.	No
Secondary	Time to reach the maximum plasma concentration (tmax) of abiraterone		Up to Day 8 of each treatment period.	No
Secondary	Area under the plasma concentration-time curve from time 0 to 24 hours postdose (AUC24) of abiraterone		Up to Day 8 of each treatment period.	No
Secondary	Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of abiraterone		Up to Day 8 of each treatment period.	No
Secondary	Time to last quantifiable plasma concentration (Tlast) of abiraterone		Up to Day 8 of each treatment period.	No
Secondary	Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone		Up to Day 8 of each treatment period.	No

External Links

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