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Triptorelin 6-month formulation for children who mature too early because of a brain hormone

Conditions
Central Precocious Puberty
MedDRA version: 18.0Level: PTClassification code 10058084Term: Precocious pubertySystem Organ Class: 10014698 - Endocrine disorders
Therapeutic area: Body processes [G] - Biological Phenomena [G16]
Registration Number
EUCTR2015-001607-30-Outside-EU/EEA
Lead Sponsor
Debiopharm International, S.A.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
A
Sex
All
Target Recruitment
44
Inclusion Criteria

1. Onset of development of sex characteristics before 8 and 9 years in girls and boys, respectively (breast development in girls or testicular enlargement in boys according to the Tanner method), and candidate to receive at least 12 months of GnRH agonist therapy after study entry.
2. Aged 2-8 years inclusive (i.e. < 9 years) for girls and 2-9 years inclusive (i.e. < 10 years) for boys at initiation of triptorelin treatment.
3. Initiation of triptorelin treatment at the latest 18 months after onset of the first signs of precocious puberty.
4. Difference (?) bone age (Greulich and Pyle method) - chronological age = 1 year.
5. Pubertal-type LH response 30 minutes following a GnRH agonist stimulation test before treatment initiation (leuprolide acetate 20 µg/kg SC) = 6 IU/L.
6. Clinical evidence of puberty, defined as Tanner Staging = 2 for breast development for girls and testicular volume = 4 mL (cc) for boys.
7. Informed consent signed by one parent or both parents (as per local requirements), by the liable parent or by the legal guardian (when applicable); assent signed by the child if = 7 years.

Are the trial subjects under 18? yes
Number of subjects for this age range: 44
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion.
2. Non-progressing isolated premature thelarche.
3. Presence of an unstable intracranial tumour or an intracranial tumour requiring neurosurgery or cerebral irradiation. Patients with hamartomas not requiring surgery are eligible.
4. Evidence of renal (creatinine > 2 x ULN) or hepatic impairment (bilirubin or ASAT > 3 x ULN).
5. Any other condition or chronic illness or treatment possibly interfering with growth or other study endpoints (e.g. chronic steroid use [except mild topical steroids], renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumour).
6. Prior or current therapy with a GnRH agonist, medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF 1).
7. Major medical or psychiatric illness that could interfere with study visits.
8. Diagnosis of short stature, i.e. > 2.25 SD below the mean height for age.
9. Positive pregnancy test.
10. Known hypersensibility to any of the test materials or related compounds.
11. Use of anticoagulants (heparin and coumarin derivatives).

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate the efficacy of triptorelin pamoate (embonate) 22.5 mg 6-month formulation IM in achieving LH suppression to prepubertal levels (defined as serum LH = 5 IU/L 30 minutes after SC GnRH agonist stimulation [leuprolide acetate 20 µg/kg SC]) at Month 6 (Day 169) in children with CPP.;Secondary Objective: Safety and pharmacokinetics of triptorelin 22.5 mg 6-month formulation in 44 patients suffering from central precocious puberty.;Primary end point(s): Percentage of children with LH suppression to prepubertal levels at Month 6;Timepoint(s) of evaluation of this end point: At month 6
Secondary Outcome Measures
NameTimeMethod
Timepoint(s) of evaluation of this end point: 1. At months 1, 2, 3, 6, 9 and 12<br>2. At months 1, 2, 3, 6, 9 and 12<br>3. Within 12 months<br>4. Within 12 months<br>5. Within 12 months<br>;Secondary end point(s): 1. Percentage of children with LH, FSH, estradiol/testosterone suppression to prepubertal levels <br>2. Triptorelin serum levels<br>3. Percentage of children with adverse events<br>4. Change from baseline in growth<br>5. Change from baseline in sexual maturation <br>
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