E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Central Precocious Puberty |
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E.1.1.1 | Medical condition in easily understood language |
Central Precocious Puberty |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073186 |
E.1.2 | Term | Central precocious puberty |
E.1.2 | System Organ Class | 100000004860 |
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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 |
The objective of the Phase 3 treatment period was to evaluate the safety and efficacy of leuprolide acetate for depot suspension in the treatment of CPP. Efficacy was evaluated based on Tanner staging and decrease of gonadotropins and sex steroids to prepubertal levels. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Phase 4 Protocol: Long-Term Post-Treatment Follow-up |
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E.3 | Principal inclusion criteria |
1. Clinical diagnosis of isosexual CPP with onset of Tanner scores of B2 (breast) or
P2 (pubic hair) earlier than age 8.0 years for girls or P2 (pubic hair) or G2
(genitalia) earlier than 9.0 years for boys.
2. Confirmation of diagnosis by a pubertal response to a GnRH stimulation test
(LH ≥ 10 U/L at baseline).
3. Chronological age less than 9.0 years for girls or less than 10.0 years for boys at
entry into the study at the time of the first injection.
4. Bone age advanced at least one year beyond chronological age by Fels Method at
entry into the study.
5. This condition may have been idiopathic or secondary to another lesion. If
secondary, therapy of the primary condition had been undertaken and stabilized.
6. No evidence of abnormal pituitary, adrenal, thyroid, and gonadal function except
for premature secretion of gonadotropins.
7. In general good health with no uncontrolled, clinically significant disease that
would mask the objectives of this protocol.
8. All the prestudy procedures were completed.
9. Eligible for therapy for at least 1 year.
10. The parent/guardian voluntarily signed the informed consent after its content was
explained. |
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E.4 | Principal exclusion criteria |
1. Irradiation to the central nervous system.
2. Prior therapy with medroxyprogesterone acetate and/or with any GnRH analog (including prior treatment with daily subcutaneous and depot formulations of leuprolide acetate). |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Breast Development in Females)
-Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Genital Development in Males) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time Frame: Weeks 4, 8, 12, 24, 36, 48, then every 6 months until end of treatment, and end of treatment day |
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E.5.2 | Secondary end point(s) |
-Mean Peak Stimulated Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Concentrations
-Mean Stimulated Estradiol Concentrations in Females
-Mean Stimulated Testosterone Concentrations in Males
-Mean Ratio of Bone Age to Chronological Age |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Hormone laboratory test results (LH suppression). Time Frame: Weeks 4, 8, 12, 24, 36, 48, and then every 6 months until end of treatment, and end of treatment day.
•Ratio of change in bone age to the change in chronological age. Time Frame: Weeks 24 and 48 then every 12 months until end of treatment and end of treatment day.
•Predicted mature height. Time Frame: Weeks 24 and 48, then every 12 months until end of treatment, and end of treatment day. |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 10 |