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

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 .

Study Overview

• Status: Completed
• Conditions: Puberty, Precocious
• Intervention / Treatment: Drug: Anastrozole; Drug: Bicalutamide

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • Research Site
• France
  • Montpellier Cedex, France, 34295
    • Research Site
• India
  • Chennai, India, 600020
    • Research Site
  • New Dehli, India, 110029
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 117036
    • Research Site
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Research Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Research Site
  • Texas
    • Temple, Texas, United States, 76508
      • Research Site
  • Washington
    • Spokane, Washington, United States, 99204
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Bicalutamide with Anastrozole; Bicalutamide in combination with Anastrozole	Drug: Anastrozole; oral; Other Names: ZD1033; Arimidex; Drug: Bicalutamide; oral; Other Names: Casodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Growth Rate (cm/Year)	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).	Assessed after 12 months treatment
Change in Growth Rate (SD Units)	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).	Assessed after 12 months treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Growth Rate (cm/Year)	Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.	Assessed after 6 months treatment
Change in Growth Rate (SD Units)	Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.	Assessed after 6 months treatment
Change in Bone Age Maturation Rate (cm/Year)	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.	Assessed after 6 and 12 months treatment
Change in Bone Age to Chronological Age Ratio	Change in bone age to chronological age ratio after 6 and 12 months treatment relative to the baseline ratio for all patients.	Assessed after 6 and 12 months of treatment
Number of Patients With Height Between 5th and 95th Percentile	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.	Assessed after 3, 6, 9 and 12 months of treatment
Change in Predicted Adult Height (PAH)	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.	Assessed after 12 months treatment
Change in Average Testicular Volume	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.	Assessed after 6 and 12 months of treatment

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Yuri E Rukazenkov, MD, AstraZeneca

Publications and helpful links

Helpful Links

• CSR-D6873C00047.pdf

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2004
• Primary Completion (Actual): May 22, 2008
• Study Completion (Actual): December 6, 2017

Study Registration Dates

• First Submitted: October 16, 2004
• First Submitted That Met QC Criteria: October 16, 2004
• First Posted (Estimate): October 18, 2004

Study Record Updates

• Last Update Posted (Actual): June 26, 2018
• Last Update Submitted That Met QC Criteria: June 25, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Testotoxicosis; Familial Male-limited Precocious Puberty (FMPP)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Androgen Antagonists; Bicalutamide; Anastrozole
• Other Study ID Numbers: D6873C00047; BATT