Clinical Trial Results:
An open-label, non-comparative, multicenter study on the efficacy, safety, and pharmacokinetics of triptorelin pamoate (embonate) 22.5 mg 6-month formulation in patients suffering from central (gonadotropin-dependent) precocious puberty
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Summary
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EudraCT number |
2015-001607-30 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
14 Jul 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
07 Apr 2016
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First version publication date |
11 Jul 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
Debio8206-CPP-301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01467882 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Debiopharm International, S.A.
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Sponsor organisation address |
Case postale 5911, Chemin Messidor 5-7, Lausanne, Switzerland, 1002
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Public contact |
Dr Eija Lundström, Debiopharm International, S.A., 41 21321 0111, eija.lundstrom@debiopharm.com
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Scientific contact |
Dr Eija Lundström, Debiopharm International, S.A., 41 21321 0111, eija.lundstrom@debiopharm.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Sep 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Jul 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of triptorelin pamoate (embonate) 22.5 mg 6-month formulation IM in achieving LH suppression to prepubertal levels (defined as serum LH ≤ 5 IU/L 30 minutes after SC GnRH agonist stimulation [leuprolide acetate 20 μg/kg SC]) at Month 6 (Day 169) in children with CPP.
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Protection of trial subjects |
After being fully informed about the trial, ethics-approved parental informed consent was signed in conformation with the Declaration of Helsinki and local laws was obtained from one or both parents (as per local requirements), by the liable parent or by the legal guardian prior to any study procedures. Assent was also collected from children aged 7 or more years. Participants were allowed to be withdrawn voluntarily or if the investigator determined the child's safety or well-being was at risk.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Apr 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 28
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Country: Number of subjects enrolled |
Mexico: 1
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Country: Number of subjects enrolled |
Chile: 15
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Worldwide total number of subjects |
44
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
44
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A group of 39 girls and 5 boys (44 children) with central precocious puberty (CPP) were enrolled by 13 centers in the USA, Chile, and Mexico. | ||||||
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Pre-assignment
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Screening details |
Girls up to age 9 and boys up to age 10 were screened for a diagnosis of central precocious puberty. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Children | ||||||
Arm description |
All children enrolled | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Triptorelin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Two intramuscular (IM) injections of triptorelin pamoate 22.5 mg 6-month formulation
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Children
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Reporting group description |
All children enrolled | ||
Subject analysis set title |
All Children - Luteinizing Hormone
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All children with luteinizing hormone values
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Subject analysis set title |
All Children - Follicle Stimulating Hormone
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All children with follicle stimulating hormone values
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Subject analysis set title |
Girls
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All girls enrolled
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Subject analysis set title |
Boys
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All boys enrolled
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Subject analysis set title |
AOC Subset
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Acute-on-chronic (AOC) Subset, defined as 50% of the population randomly assigned
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End point title |
Percentage of children with LH suppression to prepubertal levels 30 minutes after leuprolide stimulation at month 6 [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at month 6
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was conducted; two sided 95% confidence interval is provided in the data table. Database constraints require only comparative groups to populate the statistical analysis module. Therefore, because this was a single arm study, the database can only state "no statistical analyses for this end point" which, while inaccurate, may appear in the record. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of children with LH suppression to prepubertal levels 30 minutes after leuprolide stimulation at months 1, 2, 3, 9 and 12 | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at months 1, 2, 3, 9 and 12
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of children maintaining LH suppression at prepubertal levels 30 minutes after leuprolide stimulation from month 6 to 12 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from Month 6 to Month 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of children with LH suppression (LH ≤ 4 IU/L)30 minutes after leuprolide stimulation at months 1, 2, 3, 6, 9 and 12 | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at months 1, 2, 3, 6, 9 and 12
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Percentage of children maintaining LH suppression at </= 4 IU/L 30 minutes after leuprolide stimulation from month 6 to 12 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from month 6 to 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline in luteinizing hormone (LH) and follicle stimulating hormone (FSH) at months 1, 2, 3, 6, 9, and 12 | ||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at months 1, 2, 3, 6, 9, and 12
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Change from baseline in estradiol levels at months 1, 2, 3, 6, 9, and 12 | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at Months 1, 2, 3, 6, 9, and 12
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Change in testosterone levels at months 1, 2, 3, 6, 9, and 12 | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at months 1, 2, 3, 6, 9, and 12
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Percentage of children with prepubertal estradiol or testosterone levels at months 1, 2, 3, 6, 9, and 12 | ||||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at months 1, 2, 3, 6, 9, and 12
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of children without higher basal LH and estradiol or testosterone 2 days after second triptorelin injection | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at 2 days after second triptorelin injection (Day 171)
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline in height-for-age Z-score and percentile per 2000 CDC growth charts at months 6 and 12 | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At months 6 and 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change in growth velocity at months 6 and 12 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At months 6 and 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants without bone age / chronological age ratio increase from baseline at months 6 and 12 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At months 6 and 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of children achieving stabilisation of sexual maturation at months 6 and 12 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At months 6 and 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of girls with regression of uterine length at months 6 and 12 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At months 6 and 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of boys with absence of progression of testis volumes at months 6 and 12 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At months 6 and 12
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
12 months
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Children
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Reporting group description |
All children enrolled | ||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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22 Nov 2011 |
The amendment was required to improve some practical and pharmacovigilance-related aspects of the study.
1. Further to a shortage of leuprolide acetate on the US market, the suppliers initially identified were removed from the protocol and study centers were able to purchase any commercial leuprolide acetate. In addition, the number of alcohol pads in the injection kit was no longer specified to accommodate different suppliers.
2. The total volume of the vial of water for injection was no longer specified to accommodate different suppliers.
3. The CT scan or MRI of the brain initially to be performed at screening could be replaced by a brain CT or MRI performed within three months of the first IMP injection.
4. Reporting of SAEs to the Sponsor was corrected to comply with the Sponsor's pharmacovigilance procedure (contact person).
5. Reporting of SAEs in case of premature discontinuation was included to accomodate the triptorelin 6-month sustained-release formulation (reporting period of 7 months [6 months + 30 days] after the last triptorelin administration). |
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25 Jan 2012 |
The amendment was required because the blood volume necessary for measurement of hormone levels post-leuprolide stimulation had increased from 1 mL to 2 mL. In addition, inclusion criterion No. 7 was modified to allow parental signature of informed consent as per local requirements.
1. Two mL of blood instead of 1 mL were required post-leuprolide stimulation because of the minimal blood volume requirement of the analytical device. Despite this increase, the volume sampled per child remained within the limits recommended by the European ethical guidelines (Directive 2001/20/EC related to GCP) and were in accordance with ICH guidelines for clinical studies in a pediatric population.
2. Inclusion criterion No. 7 was modified (bold characters) to read: "Informed consent signed by one parent or both parents (as per local requirements), by the liable parent or by the legal guardian (when applicable); assent signed by the child if ≥ 7 years". |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
