Central Precocious Puberty
Conditions
Brief summary
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.
Interventions
DRUGTriptorelin pamoate 15mg
Intramuscular injection (IM)
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 10 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Luteinising Hormone (LH) Suppression After Gonadotropin-Releasing Hormone (GnRH) Stimulation | At Month 3 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With LH Suppression After GnRH Stimulation | At Months 6 and 12 | 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). |
| Change From Baseline in Peak LH and FSH Level After GnRH Stimulation | Baseline (Day 1) and at Months 3, 6 and 12 | 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. |
| Percentage of Participants With Prepubertal Levels of Sex Steroids | At Months 3, 6, 9 and 12 | 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. |
| Change From Baseline in Estradiol Levels | Baseline (Day 1) and at Months 3, 6 ,9 and 12 | 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. |
| Change From Baseline in Testosterone Levels | Baseline (Day 1) and at Months 3, 6 ,9 and 12 | 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. |
| Percentage of Participants With Change From Baseline in Pubertal Stage | Baseline (Day 1) and at Months 6 and 12 | 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. |
| Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Baseline (Day 1) and at Months 6 and 12 | 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. |
| Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | Baseline (Day 1) and at Months 3, 6, 9 and 12 | 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. |
| Change From Baseline in Auxological Parameter: Weight | Baseline (Day 1) and at Months 3, 6, 9 and 12 | 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. |
| Change From Baseline in Auxological Parameter: Growth Velocity | Baseline (Day 1) and at Months 3, 6, 9 and 12 | 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. |
| Change From Baseline in Auxological Parameter: Body Mass Index (BMI) | Baseline (Day 1) and at Months 3, 6, 9 and 12 | 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. |
| Change From Baseline in Bone Age (BA) | Baseline (Day 1) and at Months 6 and 12 | 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. |
| Change From Baseline Difference Between BA and Chronological Age (CA) | Baseline (Day 1) and at Months 6 and 12 | 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. |
| Change From Baseline in Uterine Length | Baseline (Day 1) and at Months 6 and12 | 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. |
| Change From Baseline of Testicular Volume | Baseline (Day 1) and at Months 6 and 12 | 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. |
| Change From Baseline in Auxological Parameter: Height | Baseline (Day 1) and at Months 3, 6, 9 and 12 | 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. |
Countries
China
Participant flow
Recruitment details
This prospective, Phase 3, open-label, single arm, 2-phase (main study phase and an extension phase) study was conducted in children with central precocious puberty (CPP) at 6 investigational sites in China.
Pre-assignment details
This study consisted of screening period (up to 28 days), main study phase (6 months) and an optional extension phase (6 months). A total of 32 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants received triptorelin pamoate 15 mg IM injection on Day 1 visit and Month 3 visit (Day 91) during the main study phase. Participants had an option to continue with the triptorelin pamoate in extension phase of the study. As per Investigator decision, eligible participants continued to receive IM injections of triptorelin pamoate on Month 6 (Day 182) and Month 9 (Day 271) during the extension phase. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Phase | Withdrawal by Parent/Guardian | 1 |
| Main Study Phase | Withdrawal by Parent/Guardian | 2 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 32 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 7.6 years STANDARD_DEVIATION 0.8 |
| Race/Ethnicity, Customized Chinese | 32 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 32 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 27 / 32 |
| serious Total, serious adverse events | 2 / 32 |
Outcome results
Primary
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
Population: The modified ITT (mITT) population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Percentage of Participants With Luteinising Hormone (LH) Suppression After Gonadotropin-Releasing Hormone (GnRH) Stimulation | 100 percentage of participants |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline Difference Between BA and Chronological Age (CA) | Month 6 | -0.44 years | Standard Deviation 0.53 |
| All Participants | Change From Baseline Difference Between BA and Chronological Age (CA) | Month 12 | -0.48 years | Standard Deviation 0.57 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Auxological Parameter: Body Mass Index (BMI) | Month 3 | 0.142 kg/meter square | Standard Deviation 0.702 |
| All Participants | Change From Baseline in Auxological Parameter: Body Mass Index (BMI) | Month 6 | 0.470 kg/meter square | Standard Deviation 0.791 |
| All Participants | Change From Baseline in Auxological Parameter: Body Mass Index (BMI) | Month 9 | 0.585 kg/meter square | Standard Deviation 0.849 |
| All Participants | Change From Baseline in Auxological Parameter: Body Mass Index (BMI) | Month 12 | 0.895 kg/meter square | Standard Deviation 1.081 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Auxological Parameter: Growth Velocity | Month 3 | -0.895 cm/year | Standard Deviation 3.637 |
| All Participants | Change From Baseline in Auxological Parameter: Growth Velocity | Month 6 | -3.769 cm/year | Standard Deviation 2.806 |
| All Participants | Change From Baseline in Auxological Parameter: Growth Velocity | Month 9 | -4.804 cm/year | Standard Deviation 2.927 |
| All Participants | Change From Baseline in Auxological Parameter: Growth Velocity | Month 12 | -2.052 cm/year | Standard Deviation 3.089 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Auxological Parameter: Height | Month 3 | 2.24 centimeter (cm) | Standard Deviation 0.62 |
| All Participants | Change From Baseline in Auxological Parameter: Height | Month 6 | 3.55 centimeter (cm) | Standard Deviation 0.69 |
| All Participants | Change From Baseline in Auxological Parameter: Height | Month 9 | 4.63 centimeter (cm) | Standard Deviation 0.81 |
| All Participants | Change From Baseline in Auxological Parameter: Height | Month 12 | 6.54 centimeter (cm) | Standard Deviation 0.88 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Auxological Parameter: Weight | Month 3 | 1.284 kilogram (kg) | Standard Deviation 1.319 |
| All Participants | Change From Baseline in Auxological Parameter: Weight | Month 6 | 2.533 kilogram (kg) | Standard Deviation 1.647 |
| All Participants | Change From Baseline in Auxological Parameter: Weight | Month 9 | 3.290 kilogram (kg) | Standard Deviation 1.899 |
| All Participants | Change From Baseline in Auxological Parameter: Weight | Month 12 | 4.818 kilogram (kg) | Standard Deviation 2.385 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | LH, Month 3 | -0.6906 IU/L | Standard Deviation 1.6417 |
| All Participants | Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | LH, Month 6 | -0.7411 IU/L | Standard Deviation 1.6606 |
| All Participants | Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | LH, Month 9 | -0.7415 IU/L | Standard Deviation 1.6817 |
| All Participants | Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | LH, Month 12 | -0.9310 IU/L | Standard Deviation 1.6367 |
| All Participants | Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | FSH, Month 3 | -2.3531 IU/L | Standard Deviation 1.8079 |
| All Participants | Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | FSH, Month 6 | -2.2307 IU/L | Standard Deviation 1.7445 |
| All Participants | Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | FSH, Month 9 | -2.0740 IU/L | Standard Deviation 1.7979 |
| All Participants | Change From Baseline in Basal LH and Follicle-Stimulating Hormone (FSH) Serum Levels | FSH, Month 12 | -1.9413 IU/L | Standard Deviation 1.6996 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Bone Age (BA) | Month 12 | 0.586 years | Standard Deviation 0.544 |
| All Participants | Change From Baseline in Bone Age (BA) | Month 6 | 0.233 years | Standard Deviation 0.307 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data for female participants were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Estradiol Levels | Month 3 | -8.0047 pg/mL | Standard Deviation 15.6905 |
| All Participants | Change From Baseline in Estradiol Levels | Month 6 | -8.3011 pg/mL | Standard Deviation 15.9093 |
| All Participants | Change From Baseline in Estradiol Levels | Month 9 | -7.7458 pg/mL | Standard Deviation 15.8683 |
| All Participants | Change From Baseline in Estradiol Levels | Month 12 | -8.6204 pg/mL | Standard Deviation 16.1359 |
Secondary
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.
Time frame: Baseline (Day 1) and at Months 3, 6 and 12
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Peak LH and FSH Level After GnRH Stimulation | LH, Month 3 | -23.0969 IU/L | Standard Deviation 17.9856 |
| All Participants | Change From Baseline in Peak LH and FSH Level After GnRH Stimulation | LH, Month 6 | -24.3596 IU/L | Standard Deviation 17.918 |
| All Participants | Change From Baseline in Peak LH and FSH Level After GnRH Stimulation | LH, Month 12 | -23.7221 IU/L | Standard Deviation 18.3669 |
| All Participants | Change From Baseline in Peak LH and FSH Level After GnRH Stimulation | FSH, Month 3 | -11.2757 IU/L | Standard Deviation 4.5026 |
| All Participants | Change From Baseline in Peak LH and FSH Level After GnRH Stimulation | FSH, Month 6 | -11.2536 IU/L | Standard Deviation 4.5267 |
| All Participants | Change From Baseline in Peak LH and FSH Level After GnRH Stimulation | FSH, Month 12 | -10.4701 IU/L | Standard Deviation 4.8424 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data for male participants were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Testosterone Levels | Month 3 | -1.3650 ng/mL | Standard Deviation 1.1734 |
| All Participants | Change From Baseline in Testosterone Levels | Month 6 | -1.3650 ng/mL | Standard Deviation 1.1734 |
| All Participants | Change From Baseline in Testosterone Levels | Month 9 | -1.3650 ng/mL | Standard Deviation 1.1734 |
| All Participants | Change From Baseline in Testosterone Levels | Month 12 | -1.3650 ng/mL | Standard Deviation 1.1734 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the female participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Uterine Length | Month 6 | -0.4012 cm | Standard Deviation 0.4391 |
| All Participants | Change From Baseline in Uterine Length | Month 12 | -0.3771 cm | Standard Deviation 0.6534 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the male participants analyzed were reported. The Number Analyzed for left and right are not consistent for each month because one participant did not have the examination on the left testicular throughout the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline of Testicular Volume | Left, Month 6 | -2.4022 mL | Standard Deviation 1.7109 |
| All Participants | Change From Baseline of Testicular Volume | Right, Month 6 | -4.7334 mL | Standard Deviation 4.4222 |
| All Participants | Change From Baseline of Testicular Volume | Left, Month 12 | -2.8840 mL | — |
| All Participants | Change From Baseline of Testicular Volume | Right, Month 12 | -6.7975 mL | Standard Deviation 6.3958 |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Breast development stage for female participants, Month 6, No change | 35.7 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Breast development stage for female participants, Month 6, Reduced | 57.1 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Breast development stage for female participants, Month 6, Increased | 3.6 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Breast development stage for female participants, Month 6, Missing | 3.6 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Genital development stage for male participants, Month 6, No change | 33.3 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Genital development stage for male participants, Month 6, Reduced | 66.7 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Genital development stage for male participants, Month 6, Increased | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Genital development stage for male participants, Month 6, Missing | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for female participants, Month 6, No change | 96.4 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for female participants, Month 6, Reduced | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for female participants, Month 6, Increased | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for female participants, Month 6, Missing | 3.6 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for male participants, Month 6, No change | 66.7 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for male participants, Month 6, Reduced | 33.3 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for male participants, Month 6, Increased | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for male participants, Month 6, Missing | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Breast development stage for female participants, Month 12, No change | 39.3 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Breast development stage for female participants, Month 12, Reduced | 50.0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Breast development stage for female participants, Month 12, Increased | 3.6 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Breast development stage for female participants, Month 12, Missing | 7.1 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Genital development stage for male participants, Month 12, No change | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Genital development stage for male participants, Month 12, Reduced | 100 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Genital development stage for male participants, Month 12, Increased | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Genital development stage for male participants, Month 12, Missing | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for female participants, Month 12, No change | 82.1 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for female participants, Month 12, Reduced | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for female participants, Month 12, Increased | 10.7 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for female participants, Month 12, Missing | 7.1 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for male participants, Month 12, No change | 66.7 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for male participants, Month 12, Reduced | 33.3 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for male participants, Month 12, Increased | 0 percentage of participants |
| All Participants | Percentage of Participants With Change From Baseline in Pubertal Stage | Pubic hair development stage for male participants, Month 12, Missing | 0 percentage of participants |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Percentage of Participants With LH Suppression After GnRH Stimulation | Month 6 | 93.5 percentage of participants |
| All Participants | Percentage of Participants With LH Suppression After GnRH Stimulation | Month 12 | 93.5 percentage of participants |
Secondary
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Percentage of Participants With Prepubertal Levels of Sex Steroids | Month 3 | 100 percentage of participants |
| All Participants | Percentage of Participants With Prepubertal Levels of Sex Steroids | Month 6 | 96.8 percentage of participants |
| All Participants | Percentage of Participants With Prepubertal Levels of Sex Steroids | Month 9 | 90.3 percentage of participants |
| All Participants | Percentage of Participants With Prepubertal Levels of Sex Steroids | Month 12 | 93.5 percentage of participants |
Secondary
Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline
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
Population: The mITT population consisted of all treated participants with at least 1 baseline and Month 3 post-baseline assessment of the primary efficacy endpoint. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Breast development stage for girls, Month 6 | 92.9 percentage of participants |
| All Participants | Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Genital development stage for boys, Month 6 | 100 percentage of participants |
| All Participants | Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Pubic hair development stage for girls, Month 6 | 96.4 percentage of participants |
| All Participants | Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Pubic hair development stage for boys, Month 6 | 100 percentage of participants |
| All Participants | Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Breast development stage for girls, Month 12 | 89.3 percentage of participants |
| All Participants | Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Genital development stage for boys, Month 12 | 100 percentage of participants |
| All Participants | Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Pubic hair development stage for girls, Month 12 | 82.1 percentage of participants |
| All Participants | Percentage of Participants With Stabilized Pubertal Stage Compared to Baseline | Pubic hair development stage for boys, Month 12 | 100 percentage of participants |