Trial Outcomes & Findings for Effects of Triptorelin Pamoate in Children With Precocious Puberty - Follow up Study (NCT NCT00909844)

NCT ID: NCT00909844

Last Updated: 2019-01-15

Results Overview

The primary objective was to assess efficacy of triptorelin pamoate 11.25 mg with respect to percentage of children maintaining a regression or stabilisation of sexual maturity (based on Tanner breast \[girls\] or genital \[boys\] pubertal stage) until end of study. Study treatment lasted until end of the therapeutic period; visits for Months 36 and 48 were optional since a child may have already finished the study at a prior visit. The Final Visit only occurred if the child did not end the study by a complete visit such as at Months 24, 36 or 48. Results are presented only for percentage of girls with regression or stabilisation of Tanner breast pubertal stage (n=34). Since only one boy was included in the study, results for this outcome measure were listed only and no statistical analysis was performed. Please also note additional post-hoc analysis for regression or stabilisation of Tanner breast pubertal stage which applied the variable Last Visit on Treatment instead of Final Visit.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

35 participants

Primary outcome timeframe

Months 12, 24, 36, 48 and Final Visit (if applicable; up to 63 months)

Results posted on

2019-01-15

Participant Flow

The study was designed as a multicentre study and included 10 investigational sites in France. This follow up study was to start on the day of the last visit (Month 6) of the phase III 2-54-52014-143 study and was to end when the Investigator judged that the patient had completed his/her treatment, i.e. at around 11 years in girls and 13 in boys.

A maximum of 35 patients could be included in this study (i.e. the number of patients who had completed the phase III 2-54-52014-143 study). A total of 35 patients were screened and enrolled in this current study (2-54-52014-159).

Participant milestones

Participant milestones
Measure
Triptorelin Pamoate 11.25 mg
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Overall Study
STARTED
35
Overall Study
COMPLETED
31
Overall Study
NOT COMPLETED
4

Reasons for withdrawal

Reasons for withdrawal
Measure
Triptorelin Pamoate 11.25 mg
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Overall Study
Adverse Event
1
Overall Study
Withdrawal by Subject
1
Overall Study
Lost to Follow-up
2

Baseline Characteristics

Effects of Triptorelin Pamoate in Children With Precocious Puberty - Follow up Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Age, Continuous
8.73 years
STANDARD_DEVIATION 1.07 • n=5 Participants
Sex: Female, Male
Female
34 Participants
n=5 Participants
Sex: Female, Male
Male
1 Participants
n=5 Participants
Weight at Pretreatment
32.4 kilogram (kg)
STANDARD_DEVIATION 6.9 • n=5 Participants

PRIMARY outcome

Timeframe: Months 12, 24, 36, 48 and Final Visit (if applicable; up to 63 months)

Population: Analysis performed on female patients in the ITT population, consisting of all enrolled female patients who received at least one injection of study treatment in this follow up study.

The primary objective was to assess efficacy of triptorelin pamoate 11.25 mg with respect to percentage of children maintaining a regression or stabilisation of sexual maturity (based on Tanner breast \[girls\] or genital \[boys\] pubertal stage) until end of study. Study treatment lasted until end of the therapeutic period; visits for Months 36 and 48 were optional since a child may have already finished the study at a prior visit. The Final Visit only occurred if the child did not end the study by a complete visit such as at Months 24, 36 or 48. Results are presented only for percentage of girls with regression or stabilisation of Tanner breast pubertal stage (n=34). Since only one boy was included in the study, results for this outcome measure were listed only and no statistical analysis was performed. Please also note additional post-hoc analysis for regression or stabilisation of Tanner breast pubertal stage which applied the variable Last Visit on Treatment instead of Final Visit.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=34 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Percentage of Children With a Stabilisation or Regression of Tanner Pubertal Stage at the End of the Study (Final Visit), Compared to Pretreatment (Month -6) and Baseline (Month 0)
Compared to Pretreatment (Month -6)
61.8 percentage of patients
Interval 43.56 to 77.83
Percentage of Children With a Stabilisation or Regression of Tanner Pubertal Stage at the End of the Study (Final Visit), Compared to Pretreatment (Month -6) and Baseline (Month 0)
Compared to Baseline (Month 0)
52.9 percentage of patients
Interval 35.13 to 70.22

SECONDARY outcome

Timeframe: Months -6, 0 and 36

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

A suppressed LH response to the GnRH test was defined as a stimulated peak of LH ≤3 international units per litre (IU/L). Percentage of patients who had a suppressed LH response to the GnRH test is reported. It should be noted that almost no hormonal data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Percentage of Patients With a Suppressed Luteinizing Hormone (LH) Response to Gonadotropin-Releasing Hormone (GnRH) Test
Pretreatment (Month -6)
0 percentage of patients
At Pretreatment, 0 patients had suppressed LH response to the GnRH test so 95% confidence interval is not applicable.
Percentage of Patients With a Suppressed Luteinizing Hormone (LH) Response to Gonadotropin-Releasing Hormone (GnRH) Test
Baseline (Month 0)
91.4 percentage of patients
Interval 76.94 to 98.2
Percentage of Patients With a Suppressed Luteinizing Hormone (LH) Response to Gonadotropin-Releasing Hormone (GnRH) Test
Month 36
100 percentage of patients
Interval 2.5 to 100.0

SECONDARY outcome

Timeframe: Months -6, 0, 12, 36 and Final Visit (up to 63 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Mean levels of oestradiol in girls or testosterone in boys are reported. It should be noted that almost no hormonal data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA)
Oestradiol at Pretreatment (Girls)
18.59 picograms per millilitre (pg/mL)
Standard Deviation 9.79
Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA)
Oestradiol at Baseline (Girls)
8.71 picograms per millilitre (pg/mL)
Standard Deviation 4.51
Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA)
Oestradiol at Month 12 (Girls)
2.50 picograms per millilitre (pg/mL)
Standard Deviation NA
No SD is presented since mean value is derived from a single patient
Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA)
Oestradiol at Month 36 (Girls)
12.20 picograms per millilitre (pg/mL)
Standard Deviation NA
No SD is presented since mean value is derived from a single patient
Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA)
Oestradiol at Final Visit (Girls)
10.00 picograms per millilitre (pg/mL)
Standard Deviation NA
No SD is presented since mean value is derived from a single patient
Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA)
Testosterone at Pretreatment (Boy)
6.80 picograms per millilitre (pg/mL)
Standard Deviation NA
No SD is presented since mean value is derived from a single patient
Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA)
Testosterone at Baseline (Boy)
0.56 picograms per millilitre (pg/mL)
Standard Deviation NA
No SD is presented since mean value is derived from a single patient

SECONDARY outcome

Timeframe: Months -6, 0 and 36

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

A suppressed FSH response to the GnRH test was defined as a stimulated peak of FSH ≤3 IU/L. Percentage of patients who had a suppressed FSH response to the GnRH test is reported. It should be noted that almost no hormonal data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Percentage of Patients With a Suppressed Follicle Stimulating Hormone (FSH) Response to GnRH Test
Pretreatment (Month -6)
0 percentage of patients
At Pretreatment, 0 patients had suppressed LH response to the GnRH test so 95% confidence interval is not applicable.
Percentage of Patients With a Suppressed Follicle Stimulating Hormone (FSH) Response to GnRH Test
Baseline (Month 0)
82.9 percentage of patients
Interval 66.35 to 93.44
Percentage of Patients With a Suppressed Follicle Stimulating Hormone (FSH) Response to GnRH Test
Month 36
0 percentage of patients
No CIs are presented since percentage value is derived from a single patient

SECONDARY outcome

Timeframe: Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Mean changes of BMI from Pretreatment and from Baseline are reported. It should be noted that only limited patient data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Body Mass Index (BMI) for Chronological Age Variation
Change from Pretreatment at Baseline
0.43 kilograms per metre squared (kg/m^2)
Standard Deviation 0.74
Body Mass Index (BMI) for Chronological Age Variation
Change from Pretreatment at Month 12
1.60 kilograms per metre squared (kg/m^2)
Standard Deviation 1.29
Body Mass Index (BMI) for Chronological Age Variation
Change from Pretreatment at Month 24
1.69 kilograms per metre squared (kg/m^2)
Standard Deviation 1.60
Body Mass Index (BMI) for Chronological Age Variation
Change from Pretreatment at Month 36
1.69 kilograms per metre squared (kg/m^2)
Standard Deviation 2.48
Body Mass Index (BMI) for Chronological Age Variation
Change from Pretreatment at Month 48
1.06 kilograms per metre squared (kg/m^2)
Standard Deviation 1.29
Body Mass Index (BMI) for Chronological Age Variation
Change from Pretreatment at Final Visit
2.39 kilograms per metre squared (kg/m^2)
Standard Deviation 1.62
Body Mass Index (BMI) for Chronological Age Variation
Change from Baseline at Month 12
1.14 kilograms per metre squared (kg/m^2)
Standard Deviation 1.00
Body Mass Index (BMI) for Chronological Age Variation
Change from Baseline at Month 24
1.43 kilograms per metre squared (kg/m^2)
Standard Deviation 1.45
Body Mass Index (BMI) for Chronological Age Variation
Change from Baseline at Month 36
1.53 kilograms per metre squared (kg/m^2)
Standard Deviation 1.62
Body Mass Index (BMI) for Chronological Age Variation
Change from Baseline at Month 48
1.34 kilograms per metre squared (kg/m^2)
Standard Deviation 0.73
Body Mass Index (BMI) for Chronological Age Variation
Change from Baseline at Final Visit
1.91 kilograms per metre squared (kg/m^2)
Standard Deviation 1.50

SECONDARY outcome

Timeframe: Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Mean changes of BMI SD score from Pretreatment and from Baseline are reported. SD score is a standard term used in growth studies and represents standard deviations calculated as the patient value minus the mean divided by the SD. SD scores vary depending on the age and sex of the child. It should be noted that only limited patient data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Pretreatment at Baseline
0.06 SD score
Standard Deviation 0.27
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Pretreatment at Month 12
0.16 SD score
Standard Deviation 0.37
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Pretreatment at Month 24
-0.01 SD score
Standard Deviation 0.37
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Pretreatment at Month 36
-0.04 SD score
Standard Deviation 0.63
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Pretreatment at Month 48
-0.27 SD score
Standard Deviation 0.68
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Pretreatment at Final Visit
0.10 SD score
Standard Deviation 0.46
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Baseline at Month 12
0.09 SD score
Standard Deviation 0.27
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Baseline at Month 24
-0.03 SD score
Standard Deviation 0.27
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Baseline at Month 36
-0.04 SD score
Standard Deviation 0.38
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Baseline at Month 48
-0.15 SD score
Standard Deviation 0.45
BMI Standard Deviation (SD) Score for Chronological Age Variation
Change from Baseline at Final Visit
0.01 SD score
Standard Deviation 0.36

SECONDARY outcome

Timeframe: Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Mean changes of height SD score from Pretreatment and from Baseline are reported. SD score is a standard term used in growth studies and represents standard deviations calculated as the patient value minus the mean divided by the SD. SD scores vary depending on the age and sex of the child. It should be noted that only limited patient data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Auxological Parameters Variations: Height SD Score
Change from Pretreatment at Baseline
0.09 SD score
Standard Deviation 0.14
Auxological Parameters Variations: Height SD Score
Change from Pretreatment at Month 12
-0.05 SD score
Standard Deviation 0.25
Auxological Parameters Variations: Height SD Score
Change from Pretreatment at Month 24
-0.24 SD score
Standard Deviation 0.43
Auxological Parameters Variations: Height SD Score
Change from Pretreatment at Month 36
-0.83 SD score
Standard Deviation 1.00
Auxological Parameters Variations: Height SD Score
Change from Pretreatment at Month 48
-1.68 SD score
Standard Deviation 0.43
Auxological Parameters Variations: Height SD Score
Change from Pretreatment at Final Visit
-0.36 SD score
Standard Deviation 0.53
Auxological Parameters Variations: Height SD Score
Change from Baseline at Month 12
-0.12 SD score
Standard Deviation 0.22
Auxological Parameters Variations: Height SD Score
Change from Baseline at Month 24
-0.27 SD score
Standard Deviation 0.43
Auxological Parameters Variations: Height SD Score
Change from Baseline at Month 36
-0.96 SD score
Standard Deviation 0.74
Auxological Parameters Variations: Height SD Score
Change from Baseline at Month 48
-1.65 SD score
Standard Deviation 0.38
Auxological Parameters Variations: Height SD Score
Change from Baseline at Final Visit
-0.43 SD score
Standard Deviation 0.50

SECONDARY outcome

Timeframe: Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Mean changes of growth velocity SD score from Pretreatment and from Baseline are reported. SD score is a standard term used in growth studies and represents standard deviations calculated as the patient value minus the mean divided by the SD. SD scores vary depending on the age and sex of the child. It should be noted that only limited patient data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Auxological Parameters Variations: Growth Velocity SD Score
Change from Pretreatment at Baseline
-1.85 SD score
Standard Deviation 2.10
Auxological Parameters Variations: Growth Velocity SD Score
Change from Pretreatment at Month 12
-2.44 SD score
Standard Deviation 2.08
Auxological Parameters Variations: Growth Velocity SD Score
Change from Pretreatment at Month 24
-3.18 SD score
Standard Deviation 2.76
Auxological Parameters Variations: Growth Velocity SD Score
Change from Pretreatment at Month 36
-6.97 SD score
Standard Deviation 5.85
Auxological Parameters Variations: Growth Velocity SD Score
Change from Pretreatment at Month 48
-6.96 SD score
Standard Deviation 5.79
Auxological Parameters Variations: Growth Velocity SD Score
Change from Pretreatment at Final Visit
-2.70 SD score
Standard Deviation 2.47
Auxological Parameters Variations: Growth Velocity SD Score
Change from Baseline at Month 12
-1.06 SD score
Standard Deviation 1.44
Auxological Parameters Variations: Growth Velocity SD Score
Change from Baseline at Month 24
-0.92 SD score
Standard Deviation 1.50
Auxological Parameters Variations: Growth Velocity SD Score
Change from Baseline at Month 36
-2.79 SD score
Standard Deviation 1.18
Auxological Parameters Variations: Growth Velocity SD Score
Change from Baseline at Month 48
-2.65 SD score
Standard Deviation 1.01
Auxological Parameters Variations: Growth Velocity SD Score
Change from Baseline at Final Visit
-1.09 SD score
Standard Deviation 1.30

SECONDARY outcome

Timeframe: Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Mean changes of weight from Pretreatment and from Baseline are reported. It should be noted that only limited patient data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Auxological Parameters Variations: Weight Variation
Change from Pretreatment at Baseline
2.49 kg
Standard Deviation 1.53
Auxological Parameters Variations: Weight Variation
Change from Pretreatment at Month 12
7.56 kg
Standard Deviation 3.47
Auxological Parameters Variations: Weight Variation
Change from Pretreatment at Month 24
10.13 kg
Standard Deviation 4.34
Auxological Parameters Variations: Weight Variation
Change from Pretreatment at Month 36
12.70 kg
Standard Deviation 7.05
Auxological Parameters Variations: Weight Variation
Change from Pretreatment at Month 48
12.20 kg
Standard Deviation 1.70
Auxological Parameters Variations: Weight Variation
Change from Pretreatment at Final Visit
13.17 kg
Standard Deviation 6.21
Auxological Parameters Variations: Weight Variation
Change from Baseline at Month 12
5.06 kg
Standard Deviation 2.79
Auxological Parameters Variations: Weight Variation
Change from Baseline at Month 24
8.21 kg
Standard Deviation 4.17
Auxological Parameters Variations: Weight Variation
Change from Baseline at Month 36
10.27 kg
Standard Deviation 5.11
Auxological Parameters Variations: Weight Variation
Change from Baseline at Month 48
10.85 kg
Standard Deviation 0.92
Auxological Parameters Variations: Weight Variation
Change from Baseline at Final Visit
10.65 kg
Standard Deviation 6.02

SECONDARY outcome

Timeframe: Months -6, 0, 12 and Final Visit (up to 63 months)

Population: Analysis performed on female patients in the ITT population, consisting of all enrolled female patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Mean change of predicted adult height SD score from Pretreatment and from Baseline are reported. SD score is a standard term used in growth studies and represents standard deviations calculated as the patient value minus the mean divided by the SD. SD scores vary depending on the age and sex of the child. It should be noted that only limited patient data was collected after Baseline; all data analysed is presented. Also note that data for this endpoint was analysed for girls only.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=34 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Predicted Adult Height SD Score
Change from Pretreatment at Baseline
0.31 SD score
Standard Deviation 0.18
Predicted Adult Height SD Score
Change from Pretreatment at Month 12
0.82 SD score
Standard Deviation NA
No SD is presented since mean value is derived from a single patient
Predicted Adult Height SD Score
Change from Pretreatment at Final Visit
2.13 SD score
Standard Deviation 0.87
Predicted Adult Height SD Score
Change from Baseline at Final Visit
1.83 SD score
Standard Deviation 0.64

SECONDARY outcome

Timeframe: Months -6, 0 and Final Visit (up to 63 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Mean change in difference between bone age and chronological age from Pretreatment and from Baseline are reported. It should be noted that only limited patient data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Bone Age Maturation
Change from Pretreatment at Baseline
-0.16 years
Standard Deviation 0.53
Bone Age Maturation
Change from Pretreatment at Final Visit
-1.61 years
Standard Deviation 1.04
Bone Age Maturation
Change from Baseline at Final Visit
-1.69 years
Standard Deviation 0.85

SECONDARY outcome

Timeframe: Months -6, 0, 12, 24, 36 and Final Visit (up to 63 months)

Population: Analysis performed on female patients in the ITT population, consisting of all enrolled female patients who received at least one injection of study treatment in this follow up study. Only patients with data available at the timepoint of testing are reported.

Percentage of girls who had a uterine length \< 36 mm are reported. It should be noted that only limited patient data was collected after Baseline; all data analysed is presented.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=34 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Percentage of Girls With a Uterine Length < 36 Millimetres (mm)
Month 12
16.7 percentage of patients
Interval 0.42 to 64.12
Percentage of Girls With a Uterine Length < 36 Millimetres (mm)
Pretreatment
42.4 percentage of patients
Interval 25.48 to 60.78
Percentage of Girls With a Uterine Length < 36 Millimetres (mm)
Baseline
41.2 percentage of patients
Interval 24.65 to 59.3
Percentage of Girls With a Uterine Length < 36 Millimetres (mm)
Month 24
50.0 percentage of patients
Interval 6.76 to 93.24
Percentage of Girls With a Uterine Length < 36 Millimetres (mm)
Month 36
0 percentage of patients
No CIs are presented since percentage value is derived from a single patient
Percentage of Girls With a Uterine Length < 36 Millimetres (mm)
Final Visit
25.0 percentage of patients
Interval 0.63 to 80.59

SECONDARY outcome

Timeframe: Months 12, 24, 36, 48 and Final Visit (if applicable; up to 63 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study.

Pubic hair was measured by the Tanner method on a scale of 1 to 6. A low grade (i.e. 1) corresponds to a pre-pubertal stage and a high grade (i.e. 5 or 6) to an adult stage. Percentage of patients who had stabilisation or regression (no change in grade or a reduced grade) of Tanner pubic hair pubertal stage is reported. Study treatment was to last until the end of the therapeutic period; visits for Months 36 and 48 were optional because if the girl was already 11 and the boy already 13, they would have finished the study at a prior visit. The Final Visit was to occur only if the child did not end the study by a complete visit such as at Months 24, 36 or 48. Please also note the additional post-hoc analysis for percentage of children with a stabilisation or regression of Tanner pubic hair pubertal stage which applied the variable Last Visit on Treatment instead of Final Visit.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Percentage of Children With a Stabilisation or Regression of Tanner Pubic Hair Pubertal Stage at the End of the Study (Final Visit), Compared to Pretreatment (Month -6) and Baseline (Month 0)
Compared to Pretreatment (Month -6)
31.4 percentage of patients
Interval 16.85 to 49.29
Percentage of Children With a Stabilisation or Regression of Tanner Pubic Hair Pubertal Stage at the End of the Study (Final Visit), Compared to Pretreatment (Month -6) and Baseline (Month 0)
Compared to Baseline (Month 0)
37.1 percentage of patients
Interval 21.47 to 55.08

POST_HOC outcome

Timeframe: Months 12, 24, 36, 48 and Last Visit on Treatment (if applicable; up to 51 months)

Population: Analysis performed on female patients in the ITT population, consisting of all enrolled female patients who received at least one injection of study treatment in this follow up study.

One primary efficacy endpoint was to assess efficacy of triptorelin pamoate 11.25 mg with respect to percentage of girls maintaining a regression or stabilisation of sexual maturity (based on Tanner breast pubertal stage) until end of study. Results reported for this primary endpoint applied the variable 'Final Visit' for comparison to Pretreatment and Baseline. Since it was determined that the majority of patients had a Final Visit \>3 months after their last injection, a post-hoc analysis of the percentage of girls with regression or stabilisation of Tanner breast pubertal stage was performed which applied the derived variable 'Last Visit on Treatment' to compare to the Pretreatment stage and to Baseline. This post-hoc analysis was judged to be appropriate since triptorelin pamoate 3-month formulation allows release of the active compound over 3 months and beyond this time, pubertal development is expected to progress.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=34 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Percentage of Girls With a Stabilisation or Regression of Tanner Breast Pubertal Stage at the End of the Study (Last Visit on Treatment), Compared to Pretreatment (Month -6) and Baseline (Month 0)
Compared to Pretreatment (Month -6)
91.2 percentage of patients
Interval 76.32 to 98.14
Percentage of Girls With a Stabilisation or Regression of Tanner Breast Pubertal Stage at the End of the Study (Last Visit on Treatment), Compared to Pretreatment (Month -6) and Baseline (Month 0)
Compared to Baseline (Month 0)
91.2 percentage of patients
Interval 76.32 to 98.14

POST_HOC outcome

Timeframe: Months 12, 24, 36, 48 and Last Visit on Treatment (if applicable; up to 51 months)

Population: Analysis performed on the ITT population, consisting of all enrolled patients who received at least one injection of study treatment in this follow up study.

One secondary efficacy endpoint in this study was the percentage of children who had stabilisation or regression (no change in grade or a reduced grade) of Tanner pubic hair pubertal stage at the end of the study. Results reported for this secondary endpoint applied the variable 'Final Visit' for comparison to Pretreatment and Baseline. Since it was determined that the majority of patients had a Final Visit \>3 months after their last injection, a post-hoc analysis of the percentage of children with regression or stabilisation of Tanner pubic hair pubertal stage was performed which applied the derived variable 'Last Visit on Treatment' for comparison to the Pretreatment stage. This post-hoc analysis was judged to be appropriate since triptorelin pamoate 3-month formulation allows release of the active compound over 3 months and beyond this time, pubertal development is expected to progress.

Outcome measures

Outcome measures
Measure
Triptorelin Pamoate 11.25 mg
n=35 Participants
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Percentage of Children With a Stabilisation or Regression of Tanner Pubic Hair Pubertal Stage at the End of the Study (Last Visit on Treatment), Compared to Pretreatment (Month -6)
57.1 percentage of patients

Adverse Events

Triptorelin Pamoate 11.25 mg

Serious events: 3 serious events
Other events: 16 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Triptorelin Pamoate 11.25 mg
n=35 participants at risk
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
General disorders
Gait disturbance
2.9%
1/35 • Number of events 1 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Injury, poisoning and procedural complications
Foot fracture
2.9%
1/35 • Number of events 1 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Musculoskeletal and connective tissue disorders
Myalgia
2.9%
1/35 • Number of events 1 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Reproductive system and breast disorders
Vaginal haemorrhage
2.9%
1/35 • Number of events 1 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs

Other adverse events

Other adverse events
Measure
Triptorelin Pamoate 11.25 mg
n=35 participants at risk
11.25 mg triptorelin pamoate (prolonged release formulation) was administered via intramuscular (i.m.) injection once every 3 months from Baseline until end of the study treatment.
Gastrointestinal disorders
Abdominal pain
17.1%
6/35 • Number of events 9 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Gastrointestinal disorders
Vomiting
5.7%
2/35 • Number of events 2 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
General disorders
Injection site pain
11.4%
4/35 • Number of events 6 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Psychiatric disorders
Insomnia
5.7%
2/35 • Number of events 2 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Reproductive system and breast disorders
Pelvic pain
5.7%
2/35 • Number of events 2 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Reproductive system and breast disorders
Vaginal haemorrhage
5.7%
2/35 • Number of events 2 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Respiratory, thoracic and mediastinal disorders
Cough
5.7%
2/35 • Number of events 2 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Nervous system disorders
Headache
8.6%
3/35 • Number of events 3 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Vascular disorders
Hot flush
8.6%
3/35 • Number of events 3 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs
Investigations
Weight increased
5.7%
2/35 • Number of events 2 • Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse event (AE) data is reported as treatment-emergent AEs

Additional Information

Medical Director, Endocrinology

Ipsen Pharma

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60