Trial Outcomes & Findings for Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis] (NCT NCT00094328)
NCT ID: NCT00094328
Last Updated: 2018-06-26
Results Overview
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).
COMPLETED
PHASE2
14 participants
Assessed after 12 months treatment
2018-06-26
Participant Flow
The first patient was enrolled on 22 November 2004 and the last patient completed the 12 months visit on 7 May 2008. Patients were allocated treatment at 9 centres in 3 countries: India, the UK and the USA. Care for two patients, transferred from one US to a new approved US centre, therefore, patients were treated at 10 centres in total
Of the 24 patients enrolled, 10 failed eligibility criteria and were classed as screening failures while the remaining 14 patients were allocated treatment.
Participant milestones
| Measure |
Open Label Bicalutamide With Anastrozole
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
|
|---|---|
|
Overall Study
STARTED
|
14
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Open Label Bicalutamide With Anastrozole
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
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|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis]
Baseline characteristics by cohort
| Measure |
Open Label Bicalutamide With Anastrozole
n=14 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
|
|---|---|
|
Age, Continuous
|
3.5 Years
n=99 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Race · Caucasian
|
12 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Race · Black
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · Hispanic/Latino
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · African/American
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · Asian
|
3 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Ethnic group · Not Applicable
|
9 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Assessed after 12 months treatmentPopulation: All treated (AT) set
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).
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=13 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
|
|---|---|
|
Change in Growth Rate (cm/Year)
|
-1.62 cm/year
Standard Deviation 5.13
|
PRIMARY outcome
Timeframe: Assessed after 12 months treatmentPopulation: All treated (AT) set
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).
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=13 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
|
|---|---|
|
Change in Growth Rate (SD Units)
|
-0.07 SD units
Standard Deviation 1.78
|
SECONDARY outcome
Timeframe: Assessed after 6 months treatmentPopulation: All treated (AT) set
Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=13 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
|
|---|---|
|
Change in Growth Rate (cm/Year)
|
-0.70 cm/year
Standard Deviation 5.77
|
SECONDARY outcome
Timeframe: Assessed after 6 months treatmentPopulation: All treated (AT) set
Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period.
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=13 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
|
|---|---|
|
Change in Growth Rate (SD Units)
|
-0.14 SD units
Standard Deviation 1.67
|
SECONDARY outcome
Timeframe: Assessed after 6 and 12 months treatmentPopulation: Calculated on All treated analysis set for those patients who had a 6-month pre study radiograph.
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.
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=6 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
|
|---|---|
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Change in Bone Age Maturation Rate (cm/Year)
After 6 months treatment
|
-2.03 cm/year
Standard Deviation 0.38
|
|
Change in Bone Age Maturation Rate (cm/Year)
After 12 months treatment
|
-2.29 cm/year
Standard Deviation 0.51
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SECONDARY outcome
Timeframe: Assessed after 6 and 12 months of treatmentPopulation: All treated (AT) set
Change in bone age to chronological age ratio after 6 and 12 months treatment relative to the baseline ratio for all patients.
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=13 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
|
|---|---|
|
Change in Bone Age to Chronological Age Ratio
After 6 months treatment
|
-0.09 Ratio
Standard Deviation 0.14
|
|
Change in Bone Age to Chronological Age Ratio
After 12 months treatment
|
-0.24 Ratio
Standard Deviation 0.18
|
SECONDARY outcome
Timeframe: Assessed after 3, 6, 9 and 12 months of treatmentPopulation: All treated (AT) set
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.
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=13 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
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|---|---|
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Number of Patients With Height Between 5th and 95th Percentile
After 3 months treatment
|
3 Participants
|
|
Number of Patients With Height Between 5th and 95th Percentile
After 6 months treatment
|
3 Participants
|
|
Number of Patients With Height Between 5th and 95th Percentile
After 9 months treatment
|
3 Participants
|
|
Number of Patients With Height Between 5th and 95th Percentile
After 12 months treatment
|
3 Participants
|
SECONDARY outcome
Timeframe: Assessed after 12 months treatmentPopulation: Calculated on All treated analysis set, however, if bone age is less than 6 years or bone age is less than 7 years and bone age\>=(chronological age-1) then PAH cannot be calculated using the Bayley and Pinneau method.
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.
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=9 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
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|---|---|
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Change in Predicted Adult Height (PAH)
|
6.21 cm
Standard Deviation 3.93
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SECONDARY outcome
Timeframe: Assessed after 6 and 12 months of treatmentPopulation: All treated (AT) set
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.
Outcome measures
| Measure |
Open Label Bicalutamide With Anastrozole
n=13 Participants
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
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|---|---|
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Change in Average Testicular Volume
After 6 months treatment
|
1.46 mL
Standard Deviation 2.29
|
|
Change in Average Testicular Volume
After 12 months treatment
|
2.69 mL
Standard Deviation 2.51
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Adverse Events
Open Label Bicalutamide With Anastrozole
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Open Label Bicalutamide With Anastrozole
n=14 participants at risk
Patients with testotoxicosis (familial male-limited precocious puberty) were given study drugs (bicalutamide in combination with anastrozole) orally once-daily for 12 months. The dosing of bicalutamide and anastrozole was independently tailored for each patient.
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|---|---|
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Gastrointestinal disorders
Abdominal Pain
|
14.3%
2/14
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Acne
|
14.3%
2/14
|
|
Investigations
Alanine Aminotransferase Increased
|
7.1%
1/14
|
|
Investigations
Aspartate Aminotransferase Increased
|
7.1%
1/14
|
|
General disorders
Asthenia
|
7.1%
1/14
|
|
Reproductive system and breast disorders
Breast Pain
|
7.1%
1/14
|
|
Reproductive system and breast disorders
Breast Tenderness
|
14.3%
2/14
|
|
Skin and subcutaneous tissue disorders
Cafe Au Lait Spots
|
7.1%
1/14
|
|
Eye disorders
Conjunctivitis
|
14.3%
2/14
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.1%
1/14
|
|
Infections and infestations
Croup Infectious
|
14.3%
2/14
|
|
Psychiatric disorders
Crying
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
7.1%
1/14
|
|
Gastrointestinal disorders
Diarrhoea
|
7.1%
1/14
|
|
Infections and infestations
Ear Infection
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Eosinophilia
|
7.1%
1/14
|
|
Injury, poisoning and procedural complications
Fall
|
7.1%
1/14
|
|
General disorders
Fatigue
|
7.1%
1/14
|
|
Infections and infestations
Furuncle
|
7.1%
1/14
|
|
Infections and infestations
Gastroenteritis
|
14.3%
2/14
|
|
Reproductive system and breast disorders
Gynaecomastia
|
50.0%
7/14
|
|
Nervous system disorders
Headache
|
21.4%
3/14
|
|
Infections and infestations
Labyrinthitis
|
7.1%
1/14
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Microcytosis
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
7.1%
1/14
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
2/14
|
|
Gastrointestinal disorders
Nausea
|
14.3%
2/14
|
|
Infections and infestations
Otitis Externa
|
7.1%
1/14
|
|
Endocrine disorders
Precocious Puberty
|
42.9%
6/14
|
|
Infections and infestations
Pyoderma
|
7.1%
1/14
|
|
General disorders
Pyrexia
|
21.4%
3/14
|
|
Infections and infestations
Respiratory Tract Infection Viral
|
7.1%
1/14
|
|
Infections and infestations
Rhinitis
|
7.1%
1/14
|
|
Immune system disorders
Seasonal Allergy
|
7.1%
1/14
|
|
Infections and infestations
Sinusitis
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Skin Hyperpigmentation
|
7.1%
1/14
|
|
Injury, poisoning and procedural complications
Skin Laceration
|
7.1%
1/14
|
|
Infections and infestations
Staphylococcal Abscess
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
7.1%
1/14
|
|
Injury, poisoning and procedural complications
Sunburn
|
7.1%
1/14
|
|
Infections and infestations
Tonsillitis
|
14.3%
2/14
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
14.3%
2/14
|
|
Infections and infestations
Varicella
|
7.1%
1/14
|
|
Infections and infestations
Viral Infection
|
7.1%
1/14
|
|
Gastrointestinal disorders
Vomiting
|
35.7%
5/14
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI agrees to collaborate with AstraZeneca on the contents and formation of any publication or disclosure and to pay due consideration to comments and opinions offered. AstraZeneca have 60 days for final manuscript review and may require that submission for publication be delayed for a further 90 days in order to file patent applications.
- Publication restrictions are in place
Restriction type: OTHER