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

• ClinicalTrials.gov Identifier: NCT00094328
• Recruitment Status: Completed
• First Posted: October 18, 2004
• Results First Posted: July 9, 2009
• Last Update Posted: June 26, 2018
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

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 .

Condition or disease	Intervention/treatment	Phase
Puberty, Precocious	Drug: Bicalutamide; Drug: Anastrozole	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 22, 2004
• Actual Primary Completion Date: May 22, 2008
• Actual Study Completion Date: December 6, 2017

Arms and Interventions

Arm	Intervention/treatment
Bicalutamide with Anastrozole; Bicalutamide in combination with Anastrozole	Drug: Bicalutamide; oral; Other Name: Casodex; Drug: Anastrozole; oral; Other Names: Arimidex; ZD1033

Outcome Measures

Primary Outcome Measures :

1. Change in Growth Rate (cm/Year) [ Time Frame: Assessed after 12 months treatment ]
   Change in growth rate after 12 months relative to the growth rate during the ≥6 month pre-study period, based on raw height data (cm/year).
2. Change in Growth Rate (SD Units) [ Time Frame: Assessed after 12 months treatment ]
   Change in growth rate after 12 months relative to the growth rate during the ≥6 month pre-study period, calculated after adjustment for the chronological age of the patient (expressed as a standard deviation [SD] score).

Secondary Outcome Measures :

1. Change in Growth Rate (cm/Year) [ Time Frame: Assessed after 6 months treatment ]
   Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.
2. Change in Growth Rate (SD Units) [ Time Frame: Assessed after 6 months treatment ]
   Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.
3. Change in Bone Age Maturation Rate (cm/Year) [ Time Frame: Assessed after 6 and 12 months treatment ]
   Radiographs were used to assess the bone age at ≥6 months pre-study, baseline, 6 and 12 months. The rate of change in bone age at baseline was calculated from a radiograph taken at least 6 months prior to study enrolment. The change in bone maturation after 6 months of treatment was calculated relative to the rate of change in bone age during the ≥ 6 months pre-study period.
4. Change in Bone Age to Chronological Age Ratio [ Time Frame: Assessed after 6 and 12 months of treatment ]
   Change in bone age to chronological age ratio after 6 and 12 months treatment relative to the baseline ratio for all patients.
5. Number of Patients With Height Between 5th and 95th Percentile [ Time Frame: Assessed after 3, 6, 9 and 12 months of treatment ]
   The number of patients whose height lies between the 5th and 95th percentiles (using the percentile tables on the WHO database) for chronological age at the 12 month assessment.
6. Change in Predicted Adult Height (PAH) [ Time Frame: Assessed after 12 months treatment ]
   Radiographs are used to assess the bone age, the change in predicted adult height (PAH) is calculated from the bone age using the Bayley and Pinneau Method. The change in PAH is be calculated by subtracting the PAH at baseline from the PAH at 12 months.
7. Change in Average Testicular Volume [ Time Frame: Assessed after 6 and 12 months of treatment ]
   Testicular volume of both testes was measured using either ultrasound or an orchidometer. Testicular volume was measured at baseline and at 6 and 12 months. The change in testicular volume from baseline was calculated for the left and right testicle as well as the average across both testes by subtracting the baseline volume from the volumes at 6 and 12 months within each patient.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 13 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Alabama

Research Site

Birmingham, Alabama, United States, 35233

United States, Florida

Research Site

Jacksonville, Florida, United States, 32207

United States, Indiana

Research Site

Indianapolis, Indiana, United States, 46202

United States, Minnesota

Research Site

Minneapolis, Minnesota, United States, 55416

United States, Oklahoma

Research Site

Tulsa, Oklahoma, United States, 74136

United States, Pennsylvania

Research Site

Philadelphia, Pennsylvania, United States, 19134

United States, South Carolina

Research Site

Greenville, South Carolina, United States, 29615

United States, Texas

Research Site

Temple, Texas, United States, 76508

United States, Washington

Research Site

Spokane, Washington, United States, 99204

Canada, Ontario

Research Site

London, Ontario, Canada, N6A 4G5

France

Research Site

Montpellier Cedex, France, 34295

India

Research Site

Chennai, India, 600020

Research Site

New Dehli, India, 110029

Russian Federation

Research Site

Moscow, Russian Federation, 117036

United Kingdom

Research Site

London, United Kingdom, WC1N 3JH

Sponsors and Collaborators

AstraZeneca

Investigators

• Study Director: Yuri E Rukazenkov, MD; AstraZeneca

More Information

Additional Information:

AstraZeneca Clinical Trial Information - Outside US  CSR-D6873C00047.pdf 

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00094328 History of Changes
• Other Study ID Numbers: D6873C00047; BATT
• First Posted: October 18, 2004
• Results First Posted: July 9, 2009
• Last Update Posted: June 26, 2018
• Last Verified: June 2018

Keywords provided by AstraZeneca:

Testotoxicosis; Familial Male-limited Precocious Puberty (FMPP)

Additional relevant MeSH terms:

Puberty, Precocious; Gonadal Disorders; Endocrine System Diseases; Anastrozole; Bicalutamide; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Androgen Antagonists