Back to resultsPediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis] (BATT)
Primary Purpose
Puberty, Precocious
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bicalutamide
Anastrozole
Sponsored by
About this trial
This is an interventional treatment trial for Puberty, Precocious focused on measuring Testotoxicosis, Familial Male-limited Precocious Puberty (FMPP)
Eligibility Criteria
Inclusion Criteria: Provision of written informed consent of parent/legal guardian and subject assent (as needed by local requirements) Male aged 2 years and over Diagnosis of testotoxicosis based on the following: Clinical features of Progressive sexual precocity documented by Tanner staging and evidence of symmetrical testicular enlargement Clinical features of significantly advanced bone age (defined as bone age of at least 12 months beyond chronological age) Pubertal levels of serum testosterone Prepubertal levels of serum gonadotropins Lack of an increase in serum gonadotropin levels following GnRH stimulation Other pathology excluded by: Undetectable plasma b human chorionic gonadotropin (bHCG). Samples with values below the LOQ will be reported as "<10 IU/L" which in the clinical setting equate to 'undetectable'. Normal levels of 17-hydroxyprogesterone (17-OHP) Normal levels of dehydroepiandrosterone sulphate (DHEAS) Naive to anti androgen receptor therapy: (Note: Ketoconazole and Spironolactone are considered acceptable as is prior use of anastrozole or other aromatase inhibitors) A documented reliable height measurement taken > 6 months prior to study enrollment. Additionally for subjects who have previously received ketoconazole or spironolactone treatment, a documented reliable height measurement taken immediately prior to beginning this treatment. (Note: for subjects who received such previous treatment only a single assessment is needed if it was taken immediately prior to beginning treatment and > 6 months prior to study entry) Subjects should be free of endocrine or other effects of previous treatment for testotoxicosis prior to study entry: to ensure this there should be 15 days or 4 drug half lives (whichever is the longer) washout period from prior medication for testotoxicosis. Exclusion Criteria: Evidence of central precocious puberty as demonstrated by GnRH stimulation test Serum concentration of total or direct bilirubin, GGT, AST or ALT greater than 1.5 times the upper limit of normal for age Serum concentration of creatinine greater than 1.5 times the upper limit of normal for age Any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk or that affects subject compliance Known hypersensitivity to any of the study medications Participation in a clinical study at the time of enrollment
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Bicalutamide with Anastrozole
Arm Description
Bicalutamide in combination with Anastrozole
Outcomes
Primary Outcome Measures
Change in Growth Rate (cm/Year)
Change in growth rate after 12 months relative to the growth rate during the ≥6 month pre-study period, based on raw height data (cm/year).
Change in Growth Rate (SD Units)
Change in growth rate after 12 months relative to the growth rate during the ≥6 month pre-study period, calculated after adjustment for the chronological age of the patient (expressed as a standard deviation [SD] score).
Secondary Outcome Measures
Change in Growth Rate (cm/Year)
Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.
Change in Growth Rate (SD Units)
Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.
Change in Bone Age Maturation Rate (cm/Year)
Radiographs were used to assess the bone age at ≥6 months pre-study, baseline, 6 and 12 months. The rate of change in bone age at baseline was calculated from a radiograph taken at least 6 months prior to study enrolment. The change in bone maturation after 6 months of treatment was calculated relative to the rate of change in bone age during the ≥ 6 months pre-study period.
Change in Bone Age to Chronological Age Ratio
Change in bone age to chronological age ratio after 6 and 12 months treatment relative to the baseline ratio for all patients.
Number of Patients With Height Between 5th and 95th Percentile
The number of patients whose height lies between the 5th and 95th percentiles (using the percentile tables on the WHO database) for chronological age at the 12 month assessment.
Change in Predicted Adult Height (PAH)
Radiographs are used to assess the bone age, the change in predicted adult height (PAH) is calculated from the bone age using the Bayley and Pinneau Method. The change in PAH is be calculated by subtracting the PAH at baseline from the PAH at 12 months.
Change in Average Testicular Volume
Testicular volume of both testes was measured using either ultrasound or an orchidometer. Testicular volume was measured at baseline and at 6 and 12 months. The change in testicular volume from baseline was calculated for the left and right testicle as well as the average across both testes by subtracting the baseline volume from the volumes at 6 and 12 months within each patient.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00094328
Brief Title
Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis]
Acronym
BATT
Official Title
An Open-label, Non-comparative, Multi-centre Study to Assess the Efficacy and Safety of Bicalutamide When Used in Combination With Anastrozole for the Treatment of Gonadotropin-independent Precocious Puberty in Boys With Testotoxicosis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
November 22, 2004 (Actual)
Primary Completion Date
May 22, 2008 (Actual)
Study Completion Date
December 6, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
Brief Summary
The primary objective of this study is to investigate whether bicalutamide given in combination with anastrozole once daily for 12 months is effective in treating testotoxicosis in boys. Testotoxicosis is a condition that causes early puberty in boys including growth in height, and development of muscles and sexual organs .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Puberty, Precocious
Keywords
Testotoxicosis, Familial Male-limited Precocious Puberty (FMPP)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bicalutamide with Anastrozole
Arm Type
Other
Arm Description
Bicalutamide in combination with Anastrozole
Intervention Type
Drug
Intervention Name(s)
Bicalutamide
Other Intervention Name(s)
Casodex
Intervention Description
oral
Intervention Type
Drug
Intervention Name(s)
Anastrozole
Other Intervention Name(s)
Arimidex, ZD1033
Intervention Description
oral
Primary Outcome Measure Information:
Title
Change in Growth Rate (cm/Year)
Description
Change in growth rate after 12 months relative to the growth rate during the ≥6 month pre-study period, based on raw height data (cm/year).
Time Frame
Assessed after 12 months treatment
Title
Change in Growth Rate (SD Units)
Description
Change in growth rate after 12 months relative to the growth rate during the ≥6 month pre-study period, calculated after adjustment for the chronological age of the patient (expressed as a standard deviation [SD] score).
Time Frame
Assessed after 12 months treatment
Secondary Outcome Measure Information:
Title
Change in Growth Rate (cm/Year)
Description
Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.
Time Frame
Assessed after 6 months treatment
Title
Change in Growth Rate (SD Units)
Description
Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.
Time Frame
Assessed after 6 months treatment
Title
Change in Bone Age Maturation Rate (cm/Year)
Description
Radiographs were used to assess the bone age at ≥6 months pre-study, baseline, 6 and 12 months. The rate of change in bone age at baseline was calculated from a radiograph taken at least 6 months prior to study enrolment. The change in bone maturation after 6 months of treatment was calculated relative to the rate of change in bone age during the ≥ 6 months pre-study period.
Time Frame
Assessed after 6 and 12 months treatment
Title
Change in Bone Age to Chronological Age Ratio
Description
Change in bone age to chronological age ratio after 6 and 12 months treatment relative to the baseline ratio for all patients.
Time Frame
Assessed after 6 and 12 months of treatment
Title
Number of Patients With Height Between 5th and 95th Percentile
Description
The number of patients whose height lies between the 5th and 95th percentiles (using the percentile tables on the WHO database) for chronological age at the 12 month assessment.
Time Frame
Assessed after 3, 6, 9 and 12 months of treatment
Title
Change in Predicted Adult Height (PAH)
Description
Radiographs are used to assess the bone age, the change in predicted adult height (PAH) is calculated from the bone age using the Bayley and Pinneau Method. The change in PAH is be calculated by subtracting the PAH at baseline from the PAH at 12 months.
Time Frame
Assessed after 12 months treatment
Title
Change in Average Testicular Volume
Description
Testicular volume of both testes was measured using either ultrasound or an orchidometer. Testicular volume was measured at baseline and at 6 and 12 months. The change in testicular volume from baseline was calculated for the left and right testicle as well as the average across both testes by subtracting the baseline volume from the volumes at 6 and 12 months within each patient.
Time Frame
Assessed after 6 and 12 months of treatment
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of written informed consent of parent/legal guardian and subject assent (as needed by local requirements)
Male aged 2 years and over
Diagnosis of testotoxicosis based on the following:
Clinical features of Progressive sexual precocity documented by Tanner staging and evidence of symmetrical testicular enlargement
Clinical features of significantly advanced bone age (defined as bone age of at least 12 months beyond chronological age)
Pubertal levels of serum testosterone
Prepubertal levels of serum gonadotropins
Lack of an increase in serum gonadotropin levels following GnRH stimulation
Other pathology excluded by:
Undetectable plasma b human chorionic gonadotropin (bHCG). Samples with values below the LOQ will be reported as "<10 IU/L" which in the clinical setting equate to 'undetectable'.
Normal levels of 17-hydroxyprogesterone (17-OHP)
Normal levels of dehydroepiandrosterone sulphate (DHEAS)
Naive to anti androgen receptor therapy:
(Note: Ketoconazole and Spironolactone are considered acceptable as is prior use of anastrozole or other aromatase inhibitors)
A documented reliable height measurement taken > 6 months prior to study enrollment. Additionally for subjects who have previously received ketoconazole or spironolactone treatment, a documented reliable height measurement taken immediately prior to beginning this treatment.
(Note: for subjects who received such previous treatment only a single assessment is needed if it was taken immediately prior to beginning treatment and > 6 months prior to study entry)
Subjects should be free of endocrine or other effects of previous treatment for testotoxicosis prior to study entry: to ensure this there should be 15 days or 4 drug half lives (whichever is the longer) washout period from prior medication for testotoxicosis.
Exclusion Criteria:
Evidence of central precocious puberty as demonstrated by GnRH stimulation test
Serum concentration of total or direct bilirubin, GGT, AST or ALT greater than 1.5 times the upper limit of normal for age
Serum concentration of creatinine greater than 1.5 times the upper limit of normal for age
Any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk or that affects subject compliance
Known hypersensitivity to any of the study medications
Participation in a clinical study at the time of enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yuri E Rukazenkov, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Research Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
Research Site
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19134
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Research Site
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Research Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Research Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4G5
Country
Canada
Facility Name
Research Site
City
Montpellier Cedex
ZIP/Postal Code
34295
Country
France
Facility Name
Research Site
City
Chennai
ZIP/Postal Code
600020
Country
India
Facility Name
Research Site
City
New Dehli
ZIP/Postal Code
110029
Country
India
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
117036
Country
Russian Federation
Facility Name
Research Site
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=402&filename=CSR-D6873C00047.pdf
Description
CSR-D6873C00047.pdf
Learn more about this trial
Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis]
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