Efficacy and Safety Study of Triptorelin 3-Month Formulation in Chinese Children With Central Precocious Puberty.

Ipsen32 enrolled

Overview

The purpose of this research was to confirm the effectiveness and safety of the study drug, Triptorelin pamoate 15mg 3-month formulation, in a Chinese population of Central Precocious Puberty (CPP) children.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Central Precocious Puberty

Interventions

Triptorelin pamoate 15mgDRUG

Intramuscular injection (IM)

Eligibility

Sex: ALLMax age: 10 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Onset of development of secondary 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: Stage II * Pubertal response of LH to GnRH stimulation test (stimulated peak LH ≥5 IU/L) * Difference between bone age (BA) (according to Greulich and Pyle method) and chronological age (CA) \>1 year * Girls with Tanner staging ≥2 for breast development and enlarged uterine length and several follicles with diameter \>4 mm in the ovary at Screening visit; boys who have testicular volume ≥4 mL at Screening visit * Age \< 9 years old for girls and \< 10 years old for boys at initiation of triptorelin treatment * Weight at least 20 kg * Subjects will qualify for the extension phase if they sign the corresponding specific consent form, are still benefiting from treatment at the end the primary study and have not experienced any unacceptable safety issues. Exclusion Criteria: * Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion * Non-progressing isolated premature thelarche * Presence of an unstable intracranial tumour or an intracranial tumour requiring neurosurgery or cerebral irradiation. Participants with hamartomas not requiring surgery are eligible * Evidence of renal (creatinine \>1.5 x upper limit of normal (ULN)) or hepatic impairment (bilirubin \>1.5 x ULN or alanine aminotransferase (ALT)/aspartate transaminase (AST) \>3 x ULN) * Any other condition or chronic illness or treatment possibly interfering with growth or other study endpoints (e.g. chronic steroid use except topical steroids, renal failure, diabetes, moderate to severe scoliosis) * Prior or current therapy with a GnRH agonist (GnRHa), medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1) * Diagnosis of short stature, i.e. \>2.25 standard deviation (SD) below the mean height for age * Major medical or psychiatric illness that could interfere with study visits * Known hypersensitivity to any of the test materials or related compounds * Use of anticoagulants (heparin and coumarin derivatives) within the 2 weeks prior to the Screening visit.

Locations (7)

Chengdu Women's and Children's Central Hospital

Chengdu, China

Jiangxi Provincial Children's Hospital

Nanchang, China

Children's Hospital of Nanjing

Nanjing, China

Tangshan Maternal & Child Health Hospital

Tangshan, China

Outcomes

Primary Outcomes

Percentage of Participants With Luteinising Hormone (LH) Suppression After Gonadotropin-Releasing Hormone (GnRH) Stimulation

The LH suppression was defined as stimulated peak LH ≤3 International Units/Liter (IU/L). The GnRH stimulation test was performed by using an intravenous (IV) injection of gonadorelin (synthetic GnRH) to stimulate gonadotrophin release and blood samples were collected after the gonadorelin injection for central assessment of serum LH levels.

Time frame: At Month 3

Secondary Outcomes

Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels

Basal LH and FSH serum concentrations were analyzed centrally. Change from baseline was defined as the value for LH and FSH levels at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 3, 6, 9 and 12

Percentage of Participants With LH Suppression After GnRH Stimulation

A synthetic GnRH (gonadorelin) was used for gonadotrophin stimulation. Blood samples were collected prior to gonadorelin injection (timepoint T0) and at 30 minutes (T30), 60 minutes (T60) and 90 minutes (T90) (±5 minutes at each timepoint) after a single IV injection of gonadorelin. A suppressed LH response to GnRH stimulation test was defined as peak LH ≤3 IU/L among the 4 timepoints T0, T30, T60 and T90).

Time frame: At Months 6 and 12

Change From Baseline in Peak LH and FSH Level After GnRH Stimulation

A synthetic GnRH was used for gonadotrophin stimulation. Blood samples were collected prior to gonadorelin injection (timepoint T0) and at 30 minutes (T30), 60 minutes (T60) and 90 minutes (T90) (±5 minutes at each timepoint) after a single IV injection of gonadorelin. The FSH response to GnRH stimulation was the peak FSH level among the 4 timepoints (T0, T30, T60 and T90). The LH response to GnRH stimulation test was defined as peak LH ≤3 IU/L among the 4 timepoints T0, T30, T60 and T90). Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Data from ClinicalTrials.gov

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Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, China

Wuxi Children's Hospital

Wuxi, China

Henan Children's Hospital, Zhengzhou Children's Hospital

Zhengzhou, China

Time frame: Baseline (Day 1) and at Months 3, 6 and 12

Percentage of Participants With Prepubertal Levels of Sex Steroids

Prepubertal sex steroids assessment included estradiol in female participants and testosterone in male participants. Prepubertal sex steroids levels were defined as: estradiol ≤20 picogram (pg)/milliliter (mL) in female participants and testosterone ≤0.3 nanogram (ng)/mL in male participants.

Time frame: At Months 3, 6, 9 and 12

Change From Baseline in Estradiol Levels

Estradiol serum concentration was analyzed centrally. Change from baseline was defined as the value for estradiol levels at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 3, 6 ,9 and 12

Change From Baseline in Testosterone Levels

Testosterone serum concentration was analyzed centrally. Change from baseline was defined as the value for testosterone levels at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 3, 6 ,9 and 12

Percentage of Participants With Change From Baseline in Pubertal Stage

Pubertal stage parameters were analyzed using Tanner method. Pubertal stage parameters included genital stage in male participants, breast stage in female participants and pubic hair stage in both sexes.

Time frame: Baseline (Day 1) and at Months 6 and 12

Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline

Time frame: Baseline (Day 1) and at Months 6 and 12

Change From Baseline in Auxological Parameter: Height

Auxological parameter including height was analyzed. Change from baseline was defined as the value for each auxological parameter at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 3, 6, 9 and 12

Change From Baseline in Auxological Parameter: Weight

Auxological parameter including weight was analyzed. Change from baseline was defined as the value for each auxological parameter at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 3, 6, 9 and 12

Change From Baseline in Auxological Parameter: Growth Velocity

Auxological parameter including growth velocity was analyzed. Change from baseline was defined as the value for each auxological parameter at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 3, 6, 9 and 12

Change From Baseline in Auxological Parameter: Body Mass Index (BMI)

Auxological parameter including BMI was analyzed. Change from baseline was defined as the value for each auxological parameter at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 3, 6, 9 and 12

Change From Baseline in Bone Age (BA)

BA was determined using X-rays of the hand and wrist. Change from baseline was defined as the value for BA at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 6 and 12

Change From Baseline Difference Between BA and Chronological Age (CA)

BA was determined using X-rays of the hand and wrist. Change from baseline was defined as the difference between BA and CA value at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 6 and 12

Change From Baseline in Uterine Length

Uterine length was determined by type B ultrasound. Change from baseline was defined as the value of uterine length at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 6 and12

Change From Baseline of Testicular Volume

Testicular volume was determined by type B ultrasound. Change from baseline was defined as the value of testicular volume at indicated timepoints minus the value at baseline. Baseline was defined as the last non-missing measurement taken prior to the first dose administered.

Time frame: Baseline (Day 1) and at Months 6 and 12