E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
testotoxicosis (precocious puberty) |
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E.1.1.1 | Medical condition in easily understood language |
condition that causes early puberty including growth in height and development of muscles and sexual organs |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063654 |
E.1.2 | Term | Testotoxicosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy defined by reduction in growth rate after 12 months treatment |
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E.2.2 | Secondary objectives of the trial |
Efficacy defined by reduction in bone maturation rate, normalization of growth rate, increase in predicted adult height, safety and tolerability, PK and PD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Provision of written infromed consent of parent/legal guardian and subject assent (as needed by local requirements)
Male aged 2 years and over
Diagnosis of testotoxicosis based on:
- Cinical features of progressive sexual precocity documented by Tanner staging and evidence of symmetrical testiclular 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 gonadotrophins;
- lack of an increase in serum gonadotrophin levels following GnRH stimulation.
Other pathology excluded by:
- undetectable plasma b human chorionic gonadotroin (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 aromatose 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 longer) washout period from prior medication for testotoxicosis.
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in growth rate (cm/year)
Change in growth rate (SD units) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed after 12 months treatment |
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E.5.2 | Secondary end point(s) |
Change in bone maturation rate.
Normalization of growth rate.
Change in predicted adult height (PAH) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessed after 12 months treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Argentina |
Brazil |
Canada |
France |
Germany |
India |
Russian Federation |
South Africa |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |