Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis] (BATT)

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