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The 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 including growth in height, and development of muscles and sexual organs.

Conditions
testotoxicosis (precocious puberty)
MedDRA version: 14.1Level: PTClassification code 10063654Term: TestotoxicosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Body processes [G] - Genetic Phenomena [G05]
Registration Number
EUCTR2012-001180-77-Outside-EU/EEA
Lead Sponsor
AstraZeneca
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
A
Sex
Male
Target Recruitment
14
Inclusion Criteria

Provision of written infromed consent of parent/legal guardian and subject assent (as needed by local requirements)
Male aged 2 years and over
Diagnosis of testotoxicosis based on:
- Cinical features of progressive sexual precocity documented by Tanner staging and evidence of symmetrical testiclular 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 gonadotrophins;
- lack of an increase in serum gonadotrophin levels following GnRH stimulation.

Other pathology excluded by:
- undetectable plasma b human chorionic gonadotroin (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 aromatose 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 longer) washout period from prior medication for testotoxicosis.

Are the trial subjects under 18? yes
Number of subjects for this age range: 14
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Efficacy defined by reduction in growth rate after 12 months treatment;Secondary Objective: Efficacy defined by reduction in bone maturation rate, normalization of growth rate, increase in predicted adult height, safety and tolerability, PK and PD.;Primary end point(s): Change in growth rate (cm/year) <br>Change in growth rate (SD units) ;Timepoint(s) of evaluation of this end point: Assessed after 12 months treatment
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Change in bone maturation rate.<br>Normalization of growth rate.<br>Change in predicted adult height (PAH);Timepoint(s) of evaluation of this end point: Assessed after 12 months treatment
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