DECAPUB: Efficacy and Safety Study of Pamoate of Triptorelin in Children With Precocious Puberty

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00564850
• Collaborator: (none)
• Enrollment: 37
• Locations: 18
• Arm: 1
• Duration (Months): 36
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the efficacy of triptorelin 11.25 mg pamoate in the delay of premature onset of puberty in girls less than 9 years and boys less than 10 years. This is measured by assessing the proportion of children who have a suppressed Luteinizing Hormone (LH) response to Gonadotropin Releasing Hormone (GnRH) test performed 3 months after injection with triptorelin 11.25 mg.

Condition or Disease	Intervention/Treatment	Phase
Precocious Puberty	Drug: Triptorelin pamoate 11.25mg (Decapeptyl® SR)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III, Multicentre, Non-comparative, Open and Single Stage Study to Assess the Efficacy and Safety of Pamoate of Triptorelin 11.25 MG in Children With Precocious Puberty
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Triptorelin pamoate 11.25mg (Decapeptyl® SR)	Drug: Triptorelin pamoate 11.25mg (Decapeptyl® SR); One intra muscular injection at day 1 and month 3.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L [3 months after the first injection of triptorelin pamoate 11.25 mg]

Secondary Outcome Measures

1. Number of Participants Whose Intravenous (i.v.) GnRH-stimulated LH Response Was ≤3 IU/L [Month 6]

2. Follicle Stimulating Hormone (FSH) Level Following GnRH Test [Screening, month 3 and 6]

3. Basal FSH Level [Month 0, 1, 2, 3, 4, 5, and 6]

4. Basal LH Level [Month 0, 1, 2, 3, 4, 5 and 6]

5. Number of Girls With Oestradiol Levels ≤ 20 pg/ml [Month 0, 1, 2, 3, 4, 5 and 6]

6. Testosterone Level [Month 0, 3 and 6]

7. Number of Girls With Inhibin B Levels < 6 pg/ml [Month 0, 3 and 6]

8. Change From Screening in Pubertal Stage (Tanner Method) at Month 6 [Between screening and month 6]

   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'.

9. Height Standard Deviation Score (SDS) [Month 0, 3 and 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.

10. Body Mass Index (BMI) SDS [Month 0, 3 and 6]

11. Change From Baseline in Growth Velocity (GV) SDS at Month 6 [Baseline and month 6]

    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.

12. Difference Between Bone Age and Chronological Age [Month 0 and 6]

    Bone age was defined according to Greulich and Pyle method. Chronological age was calculated using the date of birth.

13. Uterine Length [Month 0, 3 and 6]

14. Triptorelin Plasma Levels [Month 1, 2, 3, 4, 5 and 6]

Eligibility Criteria

Criteria

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

Inclusion Criteria in the screening phase:

• Onset of sex characteristics (Tanner method) breast development in girls or testicular enlargement in boys before the age of 8 years in girls and 9 years in boys.

• Weight ≥ 20 kg.

Inclusion Criteria in the treatment phase:

• Proven central precocious puberty defined as onset of sex characteristics development (according to Tanner method) diagnosed before the age of 8 years in girls and 9 years in boys.

• Age at evaluation less than 9 years for girls and 10 years for boys.

• A pubertal response of LH to GnRH test in both sexes (stimulated LH ≥ 5 IU/l).

• Difference Bone age (BA) (according to Greulich et Pyle method) - Chronological age (CA) > 1 year.

• Testosterone level ≥ 0.5 ng/ml in boys.

Exclusion Criteria:

• Patient with a peripheral precocious puberty: extrapituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroids secretion.

• Patient with a cerebral tumour requiring a neurosurgery or cerebral irradiation.

• Patient with a Body Weight ≥ 125% of the ideal weight for the height and age (growth curves).

• The patient has received a previous treatment with a GnRH analogue, or medroxyprogesterone or cyproterone acetate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Hotel-Dieu (CHU)	Angers		France	49033
2	Hôpital Saint-Jacques	Besancon		France	25030
3	Medical Centre	Bordeaux		France	33000
4	Hôpital du Bocage	Dijon		France	21034
5	Hôpital Flaubert	Le Havre		France	76083
6	Hôpital Jeanne de Flandre	Lille		France	59037
7	Hôpital Debrousse	Lyon		France	69322
8	Hôpital de la Timone Enfants	Marseille		France	13385
9	Hôpital Archet 2	Nice		France	06202
10	Hôpital Trousseau	Paris		France	75012
11	Hôpital St-Vincent de Paul	Paris		France	75014
12	Hôpital Necker - Enfants Malades	Paris		France	75015
13	Hôpital Robert Debré	Paris		France	75019
14	American Memorial Hospital	Reims		France	51092
15	Hôpital Charles Nicolle	Rouen		France	76031
16	Hôpital Hautepierre	Strasbourg		France	67100
17	Hôpital de la Gespe	Tarbes		France	65013
18	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: NCT00564850
• Other Study ID Numbers: 2-54-52014-143; 2005-005644-11
• First Posted: Nov 28, 2007
• Last Update Posted: Nov 22, 2019
• Last Verified: Nov 1, 2019

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

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Period Title: Overall Study
STARTED	37
COMPLETED	35
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Overall Participants	37
Age (Count of Participants)
<=18 years	37 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.2 (1.1)
Sex: Female, Male (Count of Participants)
Female	36 97.3%
Male	1 2.7%
Region of Enrollment (participants) [Number]
France	37 100%
Weight (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	32.76 (7.36)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L
Time Frame	3 months after the first injection of triptorelin pamoate 11.25 mg

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Yes [ITT (n=37)]	31 83.8%
No [ITT (n=37)]	6 16.2%
Yes [mITT (n=34)]	31 83.8%
No [mITT (n=34)]	3 8.1%
Yes [PP (n=32)]	30 81.1%
No [PP (n=32)]	2 5.4%

2. Secondary Outcome

Title	Number of Participants Whose Intravenous (i.v.) GnRH-stimulated LH Response Was ≤3 IU/L
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Yes (n=37)	32 86.5%
No (n=37)	5 13.5%

3. Secondary Outcome

Title	Follicle Stimulating Hormone (FSH) Level Following GnRH Test
Time Frame	Screening, month 3 and 6

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population. 3 participants and 2 participants had missing data at month 3 and month 6 respectively.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Screening (n=37)	11.84 (3.23)
Month 3 (n=34)	2.26 (2.5)
Month 6 (n=35)	2.34 (1.65)

4. Secondary Outcome

Title	Basal FSH Level
Time Frame	Month 0, 1, 2, 3, 4, 5, and 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Month 0 (screening, n=37)	4.13 (2.65)
Month 1 (n=35)	0.67 (0.53)
Month 2 (n=36)	1.07 (0.82)
Month 3 (n=35)	1.11 (0.73)
Month 4 (n=35)	0.78 (0.39)
Month 5 (n=34)	1.41 (2.09)
Month 6 (n=35)	1.36 (1.24)

5. Secondary Outcome

Title	Basal LH Level
Time Frame	Month 0, 1, 2, 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Month 0 (screening, n=37)	1.49 (1.78)
Month 1 (n=35)	0.42 (0.22)
Month 2 (n=36)	0.42 (0.31)
Month 3 (n=35)	0.43 (0.27)
Month 4 (n=35)	0.43 (0.23)
Month 5 (n=34)	0.48 (0.70)
Month 6 (n=35)	0.44 (0.42)

6. Secondary Outcome

Title	Number of Girls With Oestradiol Levels ≤ 20 pg/ml
Time Frame	Month 0, 1, 2, 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	36
Yes - month 0 (n=36)	22 59.5%
No - month 0 (n=36)	14 37.8%
Yes - month 1 (n=34)	34 91.9%
No - month 1 (n=34)	0 0%
Yes - month 2 (n=35)	34 91.9%
No - month 2 (n=35)	1 2.7%
Yes - month 3 (n=34)	33 89.2%
No - month 3 (n=34)	1 2.7%
Yes - month 4 (n=34)	34 91.9%
No - month 4 (n=34)	0 0%
Yes - month 5 (n=33)	33 89.2%
No - month 5 (n=33)	0 0%
Yes - month 6 (n=34)	33 89.2%
No - month 6 (n=34)	1 2.7%

7. Secondary Outcome

Title	Testosterone Level
Time Frame	Month 0, 3 and 6

Outcome Measure Data

Analysis Population Description

Testosterone level from the male patient in the ITT population.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	1
Month 0 (screening)	2.0
Month 3	0.12
Month 6	0.16

8. Secondary Outcome

Title	Number of Girls With Inhibin B Levels < 6 pg/ml
Time Frame	Month 0, 3 and 6

Outcome Measure Data

Analysis Population Description

Analysis was performed on female patients in the ITT population. 2 participants had missing data at month 3 and month 6.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	36
Yes - month 0 (screening, n=36)	18 48.6%
No - month 0 (screening, n=36)	18 48.6%
Yes - month 3 (n=34)	33 89.2%
No - month 3 (n=34)	1 2.7%
Yes - month 6 (n=34)	32 86.5%
No - month 6 (n=34)	2 5.4%

9. Secondary Outcome

Title	Change From Screening in Pubertal Stage (Tanner Method) at Month 6
Description	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'.
Time Frame	Between screening and month 6

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population. 2 participants had missing data for pubic hair stage and breast stage.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Pubic hair stage stabilised or reduced (n=35)	30 81.1%
Pubic hair stage increased (n=35)	5 13.5%
Breast stage stabilised or reduced (n=34)	32 86.5%
Breast stage increased (n=34)	2 5.4%
Penis stage stabilised or reduced (n=1)	1 2.7%
Penis stage increased (n=1)	0 0%

10. Secondary Outcome

Title	Height Standard Deviation Score (SDS)
Description	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.
Time Frame	Month 0, 3 and 6

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population. 2 participants had missing data at month 6.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Month 0 (baseline, n=37)	1.25 (1.14)
Month 3 (n=37)	1.32 (1.16)
Month 6 (n=35)	1.32 (1.16)

11. Secondary Outcome

Title	Body Mass Index (BMI) SDS
Time Frame	Month 0, 3 and 6

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population. 1 and 2 participants had missing data at month 0 and month 6 respectively.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Month 0 (baseline, n=36)	0.58 (0.85)
Month 3 (n=37)	0.64 (0.89)
Month 6 (n=35)	0.60 (0.78)

12. Secondary Outcome

Title	Change From Baseline in Growth Velocity (GV) SDS at Month 6
Description	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.
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Mean (Standard Deviation) [SD score]	-1.95 (2.07)

13. Secondary Outcome

Title	Difference Between Bone Age and Chronological Age
Description	Bone age was defined according to Greulich and Pyle method. Chronological age was calculated using the date of birth.
Time Frame	Month 0 and 6

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population. 33 participants were assessed. 4 participants had missing data at month 6.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Month 0 (screening, n=37)	2.09 (0.91)
Month 6 (n=33)	2.02 (0.88)

14. Secondary Outcome

Title	Uterine Length
Time Frame	Month 0, 3 and 6

Outcome Measure Data

Analysis Population Description

Analysis was performed on female patients in the ITT population. 2 participants had missing data at month 3 and 6.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	36
Month 0 (screening, n=35)	37.6 (10.6)
Month 3 (n=34)	37.4 (8.2)
Month 6 (n=34)	36.8 (6.9)

15. Secondary Outcome

Title	Triptorelin Plasma Levels
Time Frame	Month 1, 2, 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
Measure Participants	37
Month 1 (n=35)	0.187 (0.115)
Month 2 (n=36)	0.048 (0.023)
Month 3 (n=35)	0.034 (0.018)
Month 4 (n=34)	0.201 (0.120)
Month 5 (n=33)	0.045 (0.023)
Month 6 (n=35)	0.030 (0.017)

Adverse Events

Arm/Group Title	Triptorelin Pamoate 11.25 mg
Arm/Group Description	11.25 mg triptorelin pamoate via intramuscular injection at baseline and month 3.
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	1/37 (2.7%)
Injury, poisoning and procedural complications
Foot fracture	1/37 (2.7%)	1
Other (Not Including Serious) Adverse Events
	Triptorelin Pamoate 11.25 mg
	Affected / at Risk (%)	# Events
Total	7/37 (18.9%)
Gastrointestinal disorders
Abdominal pain	4/37 (10.8%)	4
General disorders
Injection site pain	2/37 (5.4%)	2
Vascular disorders
Hot flush	2/37 (5.4%)	2

Limitations/Caveats

[Not Specified]

More Information

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.