Trial record 13 of 53 for:    "Adrenal Hyperplasia, Congenital" [DISEASE]

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
  Purpose

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.


Condition Intervention Phase
21-hydroxylase Deficiency
Drug: Abiraterone acetate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multiple-Dose, Dose-Finding Study of Abiraterone Acetate in Adult Women With 21-Hydroxylase Deficiency

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

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 [ 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 6
Study Start Date: December 2011
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495910

Locations
United States, Illinois
Chicago, Illinois, United States
United States, Michigan
Ann Arbor, Michigan, United States
United States, Texas
Dallas, Texas, United States
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT01495910     History of Changes
Other Study ID Numbers: CR100007, 212082HPL1002
Study First Received: November 23, 2011
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
21-hydroxylase deficiency
Androstenedione
Abiraterone acetate
Pharmacokinetics
Pharmacodynamics
Dose-finding

Additional relevant MeSH terms:
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on August 18, 2014