Clinical trial NCT00094328: Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis]
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Puberty, Precocious
Keywords: Testotoxicosis
Familial Male-limited Precocious Puberty (FMPP)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2004-10-18
Enrollment: 14
Sex: MALE
Minimum age (years): 2
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 .


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

Primary outcomes:
measure: Change in Growth Rate (cm/Year)
timeFrame: Assessed after 12 months treatment
measure: Change in Growth Rate (SD Units)
timeFrame: Assessed after 12 months treatment
Secondary outcomes:
measure: Change in Growth Rate (cm/Year)
timeFrame: Assessed after 6 months treatment
measure: Change in Growth Rate (SD Units)
timeFrame: Assessed after 6 months treatment
measure: Change in Bone Age Maturation Rate (cm/Year)
timeFrame: Assessed after 6 and 12 months treatment
measure: Change in Bone Age to Chronological Age Ratio
timeFrame: Assessed after 6 and 12 months of treatment
measure: Number of Patients With Height Between 5th and 95th Percentile
timeFrame: Assessed after 3, 6, 9 and 12 months of treatment
measure: Change in Predicted Adult Height (PAH)
timeFrame: Assessed after 12 months treatment
measure: Change in Average Testicular Volume
timeFrame: Assessed after 6 and 12 months of treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Tulsa
country: United States
facility: Research Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Temple
country: United States
facility: Research Site
state: Texas
city: Spokane
country: United States
facility: Research Site
state: Washington
city: London
country: Canada
facility: Research Site
state: Ontario
city: Montpellier Cedex
country: France
facility: Research Site
city: Chennai
country: India
facility: Research Site
city: New Dehli
country: India
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Yuri E Rukazenkov, MD
role: STUDY_DIRECTOR
References: