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

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00909844
• Collaborator: (none)
• Enrollment: 35
• Locations: 10
• Arm: 1
• Duration (Months): 93
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of the protocol is to assess the efficacy of triptorelin 11.25 mg with respect to the proportion of children who maintain a regression or stabilisation of sexual maturity until the end of the study.

Condition or Disease	Intervention/Treatment	Phase
Precocious Puberty	Drug: Triptorelin (I.N.N.)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Follow-up of the Phase III, Multicentre, Non Comparative, One Single Group, Open Study to Assess the Long-term Efficacy and Tolerability of Pamoate of Triptorelin 11.25 mg in Children With Precocious Puberty
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Triptorelin	Drug: Triptorelin (I.N.N.); Decapeptyl® SR 11.25mg

Outcome Measures

Primary Outcome Measures

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

   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.

Secondary Outcome Measures

1. Percentage of Patients With a Suppressed Luteinizing Hormone (LH) Response to Gonadotropin-Releasing Hormone (GnRH) Test [Months -6, 0 and 36]

   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.

2. Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA) [Months -6, 0, 12, 36 and Final Visit (up to 63 months)]

   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.

3. Percentage of Patients With a Suppressed Follicle Stimulating Hormone (FSH) Response to GnRH Test [Months -6, 0 and 36]

   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.

4. Body Mass Index (BMI) for Chronological Age Variation [Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)]

   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.

5. BMI Standard Deviation (SD) Score for Chronological Age Variation [Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)]

   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.

6. Auxological Parameters Variations: Height SD Score [Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)]

   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.

7. Auxological Parameters Variations: Growth Velocity SD Score [Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)]

   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.

8. Auxological Parameters Variations: Weight Variation [Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)]

   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.

9. Predicted Adult Height SD Score [Months -6, 0, 12 and Final Visit (up to 63 months)]

   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.

10. Bone Age Maturation [Months -6, 0 and Final Visit (up to 63 months)]

    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.

11. Percentage of Girls With a Uterine Length < 36 Millimetres (mm) [Months -6, 0, 12, 24, 36 and Final Visit (up to 63 months)]

    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.

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

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The child must have completed study 2-54-52014-143

• The child must have an effective response to 2 injections of triptorelin 11.25 mg according to investigator's evaluation with no significant treatment side effects

Exclusion Criteria:

• The patient has a known hypersensitivity to any of the test materials or related compounds

• The patient is unable or unwilling to comply fully with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Hôtel Dieu (CHU)	Angers		France	49033
2	Medical Centre	Bordeaux		France	33000
3	Hôpital Flaubert	Le Havre		France	76083
4	Hôpital Archet II	Nice		France	06202
5	Hôpital Robert Debré	Paris		France	75019
6	American Memorial Hospital	Reims		France	51092
7	Hôpital Charles Nicolle	Rouen		France	76031
8	Hôpital Hautepierre	Strasbourg		France	67100
9	Hôpital de la Gespe	Tarbes		France	65013
10	Hôpital des Enfants	Toulouse		France	31026

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT00909844
• Other Study ID Numbers: 2-54-52014-159; 2008-000565-39
• First Posted: May 29, 2009
• Last Update Posted: Jan 15, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Puberty, Precocious; Triptorelin Pamoate

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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).

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	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.
Period Title: Overall Study
STARTED	35
COMPLETED	31
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	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 Participants	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.73 (1.07)
Sex: Female, Male (Count of Participants)
Female	34 97.1%
Male	1 2.9%
Weight at Pretreatment (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	32.4 (6.9)

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	Months 12, 24, 36, 48 and Final Visit (if applicable; up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	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.
Measure Participants	34
Compared to Pretreatment (Month -6)	61.8
Compared to Baseline (Month 0)	52.9

2. Secondary Outcome

Title	Percentage of Patients With a Suppressed Luteinizing Hormone (LH) Response to Gonadotropin-Releasing Hormone (GnRH) Test
Description	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.
Time Frame	Months -6, 0 and 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Pretreatment (Month -6)	0
Baseline (Month 0)	91.4
Month 36	100

3. Secondary Outcome

Title	Levels of Oestradiol in Girls or Testosterone in Boys Both Measured by Radioimmunoassay (RIA)
Description	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.
Time Frame	Months -6, 0, 12, 36 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Oestradiol at Pretreatment (Girls)	18.59 (9.79)
Oestradiol at Baseline (Girls)	8.71 (4.51)
Oestradiol at Month 12 (Girls)	2.50 (NA)
Oestradiol at Month 36 (Girls)	12.20 (NA)
Oestradiol at Final Visit (Girls)	10.00 (NA)
Testosterone at Pretreatment (Boy)	6.80 (NA)
Testosterone at Baseline (Boy)	0.56 (NA)

4. Secondary Outcome

Title	Percentage of Patients With a Suppressed Follicle Stimulating Hormone (FSH) Response to GnRH Test
Description	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.
Time Frame	Months -6, 0 and 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Pretreatment (Month -6)	0
Baseline (Month 0)	82.9
Month 36	0

5. Secondary Outcome

Title	Body Mass Index (BMI) for Chronological Age Variation
Description	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.
Time Frame	Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Change from Pretreatment at Baseline	0.43 (0.74)
Change from Pretreatment at Month 12	1.60 (1.29)
Change from Pretreatment at Month 24	1.69 (1.60)
Change from Pretreatment at Month 36	1.69 (2.48)
Change from Pretreatment at Month 48	1.06 (1.29)
Change from Pretreatment at Final Visit	2.39 (1.62)
Change from Baseline at Month 12	1.14 (1.00)
Change from Baseline at Month 24	1.43 (1.45)
Change from Baseline at Month 36	1.53 (1.62)
Change from Baseline at Month 48	1.34 (0.73)
Change from Baseline at Final Visit	1.91 (1.50)

6. Secondary Outcome

Title	BMI Standard Deviation (SD) Score for Chronological Age Variation
Description	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.
Time Frame	Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Change from Pretreatment at Baseline	0.06 (0.27)
Change from Pretreatment at Month 12	0.16 (0.37)
Change from Pretreatment at Month 24	-0.01 (0.37)
Change from Pretreatment at Month 36	-0.04 (0.63)
Change from Pretreatment at Month 48	-0.27 (0.68)
Change from Pretreatment at Final Visit	0.10 (0.46)
Change from Baseline at Month 12	0.09 (0.27)
Change from Baseline at Month 24	-0.03 (0.27)
Change from Baseline at Month 36	-0.04 (0.38)
Change from Baseline at Month 48	-0.15 (0.45)
Change from Baseline at Final Visit	0.01 (0.36)

7. Secondary Outcome

Title	Auxological Parameters Variations: Height SD Score
Description	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.
Time Frame	Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Change from Pretreatment at Baseline	0.09 (0.14)
Change from Pretreatment at Month 12	-0.05 (0.25)
Change from Pretreatment at Month 24	-0.24 (0.43)
Change from Pretreatment at Month 36	-0.83 (1.00)
Change from Pretreatment at Month 48	-1.68 (0.43)
Change from Pretreatment at Final Visit	-0.36 (0.53)
Change from Baseline at Month 12	-0.12 (0.22)
Change from Baseline at Month 24	-0.27 (0.43)
Change from Baseline at Month 36	-0.96 (0.74)
Change from Baseline at Month 48	-1.65 (0.38)
Change from Baseline at Final Visit	-0.43 (0.50)

8. Secondary Outcome

Title	Auxological Parameters Variations: Growth Velocity SD Score
Description	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.
Time Frame	Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Change from Pretreatment at Baseline	-1.85 (2.10)
Change from Pretreatment at Month 12	-2.44 (2.08)
Change from Pretreatment at Month 24	-3.18 (2.76)
Change from Pretreatment at Month 36	-6.97 (5.85)
Change from Pretreatment at Month 48	-6.96 (5.79)
Change from Pretreatment at Final Visit	-2.70 (2.47)
Change from Baseline at Month 12	-1.06 (1.44)
Change from Baseline at Month 24	-0.92 (1.50)
Change from Baseline at Month 36	-2.79 (1.18)
Change from Baseline at Month 48	-2.65 (1.01)
Change from Baseline at Final Visit	-1.09 (1.30)

9. Secondary Outcome

Title	Auxological Parameters Variations: Weight Variation
Description	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.
Time Frame	Months -6, 0, 12, 24, 36, 48 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Change from Pretreatment at Baseline	2.49 (1.53)
Change from Pretreatment at Month 12	7.56 (3.47)
Change from Pretreatment at Month 24	10.13 (4.34)
Change from Pretreatment at Month 36	12.70 (7.05)
Change from Pretreatment at Month 48	12.20 (1.70)
Change from Pretreatment at Final Visit	13.17 (6.21)
Change from Baseline at Month 12	5.06 (2.79)
Change from Baseline at Month 24	8.21 (4.17)
Change from Baseline at Month 36	10.27 (5.11)
Change from Baseline at Month 48	10.85 (0.92)
Change from Baseline at Final Visit	10.65 (6.02)

10. Secondary Outcome

Title	Predicted Adult Height SD Score
Description	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.
Time Frame	Months -6, 0, 12 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	34
Change from Pretreatment at Baseline	0.31 (0.18)
Change from Pretreatment at Month 12	0.82 (NA)
Change from Pretreatment at Final Visit	2.13 (0.87)
Change from Baseline at Final Visit	1.83 (0.64)

11. Secondary Outcome

Title	Bone Age Maturation
Description	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.
Time Frame	Months -6, 0 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Change from Pretreatment at Baseline	-0.16 (0.53)
Change from Pretreatment at Final Visit	-1.61 (1.04)
Change from Baseline at Final Visit	-1.69 (0.85)

12. Secondary Outcome

Title	Percentage of Girls With a Uterine Length < 36 Millimetres (mm)
Description	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.
Time Frame	Months -6, 0, 12, 24, 36 and Final Visit (up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	34
Pretreatment	42.4
Baseline	41.2
Month 12	16.7
Month 24	50.0
Month 36	0
Final Visit	25.0

13. Secondary Outcome

Title	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)
Description	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.
Time Frame	Months 12, 24, 36, 48 and Final Visit (if applicable; up to 63 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Compared to Pretreatment (Month -6)	31.4
Compared to Baseline (Month 0)	37.1

14. Post-Hoc Outcome

Title	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)
Description	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.
Time Frame	Months 12, 24, 36, 48 and Last Visit on Treatment (if applicable; up to 51 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	34
Compared to Pretreatment (Month -6)	91.2
Compared to Baseline (Month 0)	91.2

15. Post-Hoc Outcome

Title	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)
Description	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.
Time Frame	Months 12, 24, 36, 48 and Last Visit on Treatment (if applicable; up to 51 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate (prolonged release formulation) was administered via i.m. injection once every 3 months from Baseline until end of the study treatment.
Measure Participants	35
Number [percentage of patients]	57.1

Adverse Events

Time Frame	Up to 51 months (up to 48 months treatment + 3 months follow up)
Adverse Event Reporting Description	Adverse event (AE) data is reported as treatment-emergent AEs
Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	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.
All Cause Mortality
	Triptorelin Pamoate 11.25 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Triptorelin Pamoate 11.25 mg
	Affected / at Risk (%)	# Events
Total	3/35 (8.6%)
General disorders
Gait disturbance	1/35 (2.9%)	1
Injury, poisoning and procedural complications
Foot fracture	1/35 (2.9%)	1
Musculoskeletal and connective tissue disorders
Myalgia	1/35 (2.9%)	1
Reproductive system and breast disorders
Vaginal haemorrhage	1/35 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Triptorelin Pamoate 11.25 mg
	Affected / at Risk (%)	# Events
Total	16/35 (45.7%)
Gastrointestinal disorders
Abdominal pain	6/35 (17.1%)	9
Vomiting	2/35 (5.7%)	2
General disorders
Injection site pain	4/35 (11.4%)	6
Investigations
Weight increased	2/35 (5.7%)	2
Nervous system disorders
Headache	3/35 (8.6%)	3
Psychiatric disorders
Insomnia	2/35 (5.7%)	2
Reproductive system and breast disorders
Pelvic pain	2/35 (5.7%)	2
Vaginal haemorrhage	2/35 (5.7%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/35 (5.7%)	2
Vascular disorders
Hot flush	3/35 (8.6%)	3

Limitations/Caveats

Since almost no hormonal data was collected after Baseline and only limited data was collected after Baseline for all other efficacy endpoints, only limited post-Baseline data is reported for the trial overall. All data analysed has been presented.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.