Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis]
Condition: Puberty, Precocious
MeSH terms: Puberty, Precocious
Intervention: Bicalutamide; Anastrozole
Intervention description: oral; oral
Intervention MeSH terms: Anastrozole; Bicalutamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: Male
Minimum age: 2 Years
Maximum age: 13 Years
Healthy volunteers: No
Keywords: Testotoxicosis; Familial Male-limited Precocious Puberty (FMPP)

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 .
    

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