Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis]

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

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 .

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