Trial Outcomes & Findings for Efficacy and Safety Study of Pamoate of Triptorelin in Children With Precocious Puberty (NCT NCT00564850)
NCT ID: NCT00564850
Last Updated: 2022-10-12
Results Overview
COMPLETED
PHASE3
37 participants
3 months after the first injection of triptorelin pamoate 11.25 mg
2022-10-12
Participant Flow
62 participants were screened, of which 37 met the study's entry criteria and received at least one dose of investigational medicinal product. 25 participants failed screening. Participants were recruited from October 2007 at 18 Hospital clinics across France.
Participant milestones
| Measure |
Triptorelin Pamoate 11.25 mg
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Overall Study
STARTED
|
37
|
|
Overall Study
COMPLETED
|
35
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Triptorelin Pamoate 11.25 mg
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Overall Study
Protocol Violation
|
2
|
Baseline Characteristics
Efficacy and Safety Study of Pamoate of Triptorelin in Children With Precocious Puberty
Baseline characteristics by cohort
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Age, Categorical
<=18 years
|
37 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
8.2 years
STANDARD_DEVIATION 1.1 • n=99 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=99 Participants
|
|
Region of Enrollment
France
|
37 participants
n=99 Participants
|
|
Weight
|
32.76 Kg
STANDARD_DEVIATION 7.36 • n=99 Participants
|
PRIMARY outcome
Timeframe: 3 months after the first injection of triptorelin pamoate 11.25 mgPopulation: Analyses performed on: * Intention to Treat (ITT): all patients having received ≥1 injection. Any subject with missing data is considered a non-responder. * Modified ITT (mITT): all ITT patients with ≥ Month 3 post-baseline assessment of primary efficacy criterion. * Per Protocol (PP): all mITT patients without major protocol deviations.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L
Yes [ITT (n=37)]
|
31 participants
Interval 68.0 to 93.8
|
|
Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L
No [ITT (n=37)]
|
6 participants
|
|
Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L
Yes [mITT (n=34)]
|
31 participants
Interval 76.3 to 98.1
|
|
Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L
No [mITT (n=34)]
|
3 participants
|
|
Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L
Yes [PP (n=32)]
|
30 participants
Interval 79.2 to 99.2
|
|
Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L
No [PP (n=32)]
|
2 participants
|
SECONDARY outcome
Timeframe: Month 6Population: Analysis was performed on Intention to Treat population (ITT) defined as all participants having received at least one injection of 11.25 mg triptorelin pamoate. "n" indicates the number of patients who had an assessment at the visit.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Number of Participants Whose Intravenous (i.v.) GnRH-stimulated LH Response Was ≤3 IU/L
Yes (n=37)
|
32 participants
Interval 71.2 to 95.5
|
|
Number of Participants Whose Intravenous (i.v.) GnRH-stimulated LH Response Was ≤3 IU/L
No (n=37)
|
5 participants
|
SECONDARY outcome
Timeframe: Screening, month 3 and 6Population: Analysis was performed on the ITT population. 3 participants and 2 participants had missing data at month 3 and month 6 respectively.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Follicle Stimulating Hormone (FSH) Level Following GnRH Test
Screening (n=37)
|
11.84 IU/L
Standard Deviation 3.23
|
|
Follicle Stimulating Hormone (FSH) Level Following GnRH Test
Month 3 (n=34)
|
2.26 IU/L
Standard Deviation 2.5
|
|
Follicle Stimulating Hormone (FSH) Level Following GnRH Test
Month 6 (n=35)
|
2.34 IU/L
Standard Deviation 1.65
|
SECONDARY outcome
Timeframe: Month 0, 1, 2, 3, 4, 5, and 6Population: Analysis was performed on the ITT population. 2 participants had missing data at month 1, 3, 4 and 6. 1 and 3 participants had missing data at month 2 and month 5 respectively.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Basal FSH Level
Month 0 (screening, n=37)
|
4.13 IU/L
Standard Deviation 2.65
|
|
Basal FSH Level
Month 1 (n=35)
|
0.67 IU/L
Standard Deviation 0.53
|
|
Basal FSH Level
Month 2 (n=36)
|
1.07 IU/L
Standard Deviation 0.82
|
|
Basal FSH Level
Month 3 (n=35)
|
1.11 IU/L
Standard Deviation 0.73
|
|
Basal FSH Level
Month 4 (n=35)
|
0.78 IU/L
Standard Deviation 0.39
|
|
Basal FSH Level
Month 5 (n=34)
|
1.41 IU/L
Standard Deviation 2.09
|
|
Basal FSH Level
Month 6 (n=35)
|
1.36 IU/L
Standard Deviation 1.24
|
SECONDARY outcome
Timeframe: Month 0, 1, 2, 3, 4, 5 and 6Population: Analysis was performed on ITT population. 2 participants had missing data at month 1, 3, 4 and 6. 1 and 3 participants had missing data at month 2 and month 5 respectively.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Basal LH Level
Month 0 (screening, n=37)
|
1.49 IU/L
Standard Deviation 1.78
|
|
Basal LH Level
Month 1 (n=35)
|
0.42 IU/L
Standard Deviation 0.22
|
|
Basal LH Level
Month 2 (n=36)
|
0.42 IU/L
Standard Deviation 0.31
|
|
Basal LH Level
Month 3 (n=35)
|
0.43 IU/L
Standard Deviation 0.27
|
|
Basal LH Level
Month 4 (n=35)
|
0.43 IU/L
Standard Deviation 0.23
|
|
Basal LH Level
Month 5 (n=34)
|
0.48 IU/L
Standard Deviation 0.70
|
|
Basal LH Level
Month 6 (n=35)
|
0.44 IU/L
Standard Deviation 0.42
|
SECONDARY outcome
Timeframe: Month 0, 1, 2, 3, 4, 5 and 6Population: Analysis was performed on female patients in the ITT population. 2 participants had missing data at month 1, 3, 4 and 6. 1 participant and 3 participants had missing data at month 2 and 5 respectively.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=36 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
Yes - month 0 (n=36)
|
22 participants
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
No - month 0 (n=36)
|
14 participants
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
Yes - month 1 (n=34)
|
34 participants
Interval 89.7 to 99.9
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
No - month 1 (n=34)
|
0 participants
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
Yes - month 2 (n=35)
|
34 participants
Interval 85.1 to 99.9
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
No - month 2 (n=35)
|
1 participants
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
Yes - month 3 (n=34)
|
33 participants
Interval 84.7 to 99.9
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
No - month 3 (n=34)
|
1 participants
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
Yes - month 4 (n=34)
|
34 participants
Interval 89.7 to 100.0
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
No - month 4 (n=34)
|
0 participants
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
Yes - month 5 (n=33)
|
33 participants
Interval 89.4 to 100.0
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
No - month 5 (n=33)
|
0 participants
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
Yes - month 6 (n=34)
|
33 participants
Interval 84.7 to 99.9
|
|
Number of Girls With Oestradiol Levels ≤ 20 pg/ml
No - month 6 (n=34)
|
1 participants
|
SECONDARY outcome
Timeframe: Month 0, 3 and 6Population: Testosterone level from the male patient in the ITT population.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=1 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Testosterone Level
Month 0 (screening)
|
2.0 ng/ml
|
|
Testosterone Level
Month 3
|
0.12 ng/ml
|
|
Testosterone Level
Month 6
|
0.16 ng/ml
|
SECONDARY outcome
Timeframe: Month 0, 3 and 6Population: Analysis was performed on female patients in the ITT population. 2 participants had missing data at month 3 and month 6.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=36 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Number of Girls With Inhibin B Levels < 6 pg/ml
Yes - month 0 (screening, n=36)
|
18 participants
|
|
Number of Girls With Inhibin B Levels < 6 pg/ml
No - month 0 (screening, n=36)
|
18 participants
|
|
Number of Girls With Inhibin B Levels < 6 pg/ml
Yes - month 3 (n=34)
|
33 participants
Interval 84.7 to 99.9
|
|
Number of Girls With Inhibin B Levels < 6 pg/ml
No - month 3 (n=34)
|
1 participants
|
|
Number of Girls With Inhibin B Levels < 6 pg/ml
Yes - month 6 (n=34)
|
32 participants
Interval 80.3 to 99.3
|
|
Number of Girls With Inhibin B Levels < 6 pg/ml
No - month 6 (n=34)
|
2 participants
|
SECONDARY outcome
Timeframe: Between screening and month 6Population: Analysis was performed on the ITT population. 2 participants had missing data for pubic hair stage and breast stage.
Pubertal stage (graded from 1 to 5 for penis and breast development, graded from 1 to 6 for pubic hair development) according to the Tanner method was collected. A low stage (i.e. 1) corresponds to a pre-pubertal stage and a high stage (i.e. 5 or 6) to an adult stage. Any increase of grade was defined as 'increased' and no change in grade or a reduced grade was defined as 'stabilised or reduced'.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Change From Screening in Pubertal Stage (Tanner Method) at Month 6
Pubic hair stage stabilised or reduced (n=35)
|
30 participants
|
|
Change From Screening in Pubertal Stage (Tanner Method) at Month 6
Pubic hair stage increased (n=35)
|
5 participants
|
|
Change From Screening in Pubertal Stage (Tanner Method) at Month 6
Breast stage stabilised or reduced (n=34)
|
32 participants
|
|
Change From Screening in Pubertal Stage (Tanner Method) at Month 6
Breast stage increased (n=34)
|
2 participants
|
|
Change From Screening in Pubertal Stage (Tanner Method) at Month 6
Penis stage stabilised or reduced (n=1)
|
1 participants
|
|
Change From Screening in Pubertal Stage (Tanner Method) at Month 6
Penis stage increased (n=1)
|
0 participants
|
SECONDARY outcome
Timeframe: Month 0, 3 and 6Population: Analysis was performed on the ITT population. 2 participants had missing data at month 6.
Standard deviation (SD) is a standard term used in growth studies and represents Standard Deviations calculated as the patient value minus the mean divided by the standard deviation. Standard Deviation Scores vary depending on the age and sex of the child.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Height Standard Deviation Score (SDS)
Month 0 (baseline, n=37)
|
1.25 SD score
Standard Deviation 1.14
|
|
Height Standard Deviation Score (SDS)
Month 3 (n=37)
|
1.32 SD score
Standard Deviation 1.16
|
|
Height Standard Deviation Score (SDS)
Month 6 (n=35)
|
1.32 SD score
Standard Deviation 1.16
|
SECONDARY outcome
Timeframe: Month 0, 3 and 6Population: Analysis was performed on the ITT population. 1 and 2 participants had missing data at month 0 and month 6 respectively.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Body Mass Index (BMI) SDS
Month 0 (baseline, n=36)
|
0.58 SD score
Standard Deviation 0.85
|
|
Body Mass Index (BMI) SDS
Month 3 (n=37)
|
0.64 SD score
Standard Deviation 0.89
|
|
Body Mass Index (BMI) SDS
Month 6 (n=35)
|
0.60 SD score
Standard Deviation 0.78
|
SECONDARY outcome
Timeframe: Baseline and month 6Population: Analysis was performed on the ITT population. If GV at screening was missing, the value was derived from data recorded between 5 to 19 months ago otherwise GV at screening was considered missing. 9 participants had missing data.
Change from baseline of GV was calculated as: GV at month 6 - GV at baseline. GV SDS was calculated using SAS algorithm. Growth velocity during the study was calculated using the two height measures as: GV = (Height at baseline - Height at screening)\*365/delay between two height measures.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Change From Baseline in Growth Velocity (GV) SDS at Month 6
|
-1.95 SD score
Standard Deviation 2.07
|
SECONDARY outcome
Timeframe: Month 0 and 6Population: Analysis was performed on the ITT population. 33 participants were assessed. 4 participants had missing data at month 6.
Bone age was defined according to Greulich and Pyle method. Chronological age was calculated using the date of birth.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Difference Between Bone Age and Chronological Age
Month 0 (screening, n=37)
|
2.09 years
Standard Deviation 0.91
|
|
Difference Between Bone Age and Chronological Age
Month 6 (n=33)
|
2.02 years
Standard Deviation 0.88
|
SECONDARY outcome
Timeframe: Month 0, 3 and 6Population: Analysis was performed on female patients in the ITT population. 2 participants had missing data at month 3 and 6.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=36 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Uterine Length
Month 0 (screening, n=35)
|
37.6 mm
Standard Deviation 10.6
|
|
Uterine Length
Month 3 (n=34)
|
37.4 mm
Standard Deviation 8.2
|
|
Uterine Length
Month 6 (n=34)
|
36.8 mm
Standard Deviation 6.9
|
SECONDARY outcome
Timeframe: Month 1, 2, 3, 4, 5 and 6Population: Analysis was performed on the Pharmacokinetics (PK) Valid population defined as all participants who received at least one injection of 11.25 mg triptorelin pamoate and had at least one PK assessment. 2 participants had data missing at month 1,3 and 6. 1, 3 and 4 participants had data missing at month 2, 4 and 5 respectively.
Outcome measures
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 Participants
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Triptorelin Plasma Levels
Month 1 (n=35)
|
0.187 ng/mL
Standard Deviation 0.115
|
|
Triptorelin Plasma Levels
Month 2 (n=36)
|
0.048 ng/mL
Standard Deviation 0.023
|
|
Triptorelin Plasma Levels
Month 3 (n=35)
|
0.034 ng/mL
Standard Deviation 0.018
|
|
Triptorelin Plasma Levels
Month 4 (n=34)
|
0.201 ng/mL
Standard Deviation 0.120
|
|
Triptorelin Plasma Levels
Month 5 (n=33)
|
0.045 ng/mL
Standard Deviation 0.023
|
|
Triptorelin Plasma Levels
Month 6 (n=35)
|
0.030 ng/mL
Standard Deviation 0.017
|
Adverse Events
Triptorelin Pamoate 11.25 mg
Serious adverse events
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 participants at risk
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Injury, poisoning and procedural complications
Foot fracture
|
2.7%
1/37 • Number of events 1
|
Other adverse events
| Measure |
Triptorelin Pamoate 11.25 mg
n=37 participants at risk
11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
10.8%
4/37 • Number of events 4
|
|
General disorders
Injection site pain
|
5.4%
2/37 • Number of events 2
|
|
Vascular disorders
Hot flush
|
5.4%
2/37 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60