Clinical Trial Results:
Study of Lupron Depot In The Treatment of Central Precocious Puberty
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Summary
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EudraCT number |
2014-004495-36 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
22 Apr 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Apr 2016
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First version publication date |
13 Jun 2015
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Other versions |
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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 |
M90-516
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00660010 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AbbVie
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Sponsor organisation address |
1 North Waukegan Road, North Chicago, IL, United States, 60064
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Public contact |
Global Medical Information, AbbVie, 001 800-633-9110,
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Scientific contact |
Kristof Chwalisz MD, AbbVie, kristof.chwalisz@abbvie.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 |
22 Apr 2009
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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 |
22 Apr 2009
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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 |
The purpose of this study is to determine if Lupron (leuprolide acetate) is safe and effective in treating children with Central Precocious Puberty (CPP), and to assess long term effects of leuprolide acetate treatment after therapy is discontinued.
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Protection of trial subjects |
Prior to the initiation of any screening or study-specific procedures, the investigator or his representative explained the nature of the study to the subject and the subject's parent or legal guardian and answered all questions regarding this study. The informed consent statement was reviewed and signed and dated by the subject's parent or legal guardian and by the person who administered the informed consent.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Jan 1991
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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: 55
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Worldwide total number of subjects |
55
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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) |
2
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Children (2-11 years) |
53
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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 |
- | ||||||||||||||||
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Pre-assignment
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Screening details |
This study included 1 treatment group and subjects were assigned the initial dosage depending on their weight. The minimum starting dose was 7.5 mg every 28 days. Study drug was discontinued either when puberty occurred at 12 years +- 6 months for males and 11 years +- 6 months for females or at the discretion of the investigator. | ||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Leuprolide Acetate 1 Month Depot | ||||||||||||||||
Arm description |
Leuprolide acetate dosing was initiated at 300 mcg/kg (minimum dose 7.5 mg) administered intramuscularly (IM) every 28 days. Incremental adjustments to dosing at 3.75 mg increments were made at each visit. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Leuprolide acetate
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Investigational medicinal product code |
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Other name |
Lupron
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Leuprolide acetate was administered monthly by intramuscular injection starting at 300 mcg/kg with adjustments of 3.75 mg upward, at subsequent clinic visits based on physical and laboratory parameters. Dosing continued until New Drug Application (NDA) was approved, or until subject no longer required leuprolide acetate to treat CPP.
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Baseline characteristics reporting groups
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Reporting group title |
Leuprolide Acetate 1 Month Depot
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Reporting group description |
Leuprolide acetate dosing was initiated at 300 mcg/kg (minimum dose 7.5 mg) administered intramuscularly (IM) every 28 days. Incremental adjustments to dosing at 3.75 mg increments were made at each visit. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Leuprolide Acetate 1 Month Depot
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Reporting group description |
Leuprolide acetate dosing was initiated at 300 mcg/kg (minimum dose 7.5 mg) administered intramuscularly (IM) every 28 days. Incremental adjustments to dosing at 3.75 mg increments were made at each visit. | ||
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End point title |
Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Breast Development in Females) [1] | ||||||||||||||||||||||
End point description |
Suppression of clinical sexual characteristics was defined as regression (improvement) or no progression of breast development in females. Tanner staging is a scale of physical development that defines primary and secondary sex characteristics including size of breasts. The final visit occurred at a mean age +/- SD of 11.05 +/- 1.14 years (range, 6.96 to 12.95 years). The intent-to-treat (ITT) population and safety analysis set were identical for the treatment period. The starting population comprised 49 females (breast development suppression). Study drug was discontinued at the initiation of puberty. N=subjects with evaluable data at given time point.
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End point type |
Primary
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End point timeframe |
Week 4, Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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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: Descriptive data were summarized for this end point per protocol. |
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Genital Development in Males) [2] | ||||||||||||||||||||||
End point description |
Suppression of clinical sexual characteristics was defined as regression (improvement) or no progression of genital development in males. Tanner staging is a scale of physical development that defines primary and secondary sex characteristics including size of genitals. The final visit occurred at a mean age +/- SD of 12.35 +/-1.35 years (range, 10.71 to 14.07 years). The intent-to-treat (ITT) population and safety analysis set were identical for the treatment period. The starting population comprised 6 males (genital development suppression). Study drug was discontinued at the initiation of puberty. N=subjects with evaluable data at given time point.
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End point type |
Primary
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End point timeframe |
Week 4, Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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| Notes [2] - 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: Descriptive data were summarized for this end point per protocol. |
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Mean Peak Stimulated Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Mean peak stimulated visit LH and FSH concentrations were assessed according to the DELFIA (registered trademark) assay. The final visit for measurement of both hormone concentrations occurred at a mean age +/- SD of 11.13 +/- 1.23 (range, 6.73 to 14.07) years. The intent-to-treat (ITT) population and safety analysis set were identical for the treatment period. The starting population comprised 49 females and 6 males. Study drug was discontinued at the initiation of puberty. N=subjects with evaluable data at given time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Mean Stimulated Estradiol Concentrations in Females | ||||||||||||||||||||||||||||
End point description |
Mean estradiol concentrations were assessed according to the DELFIA (registered trademark) assay. The lower limit of quantitation for estradiol is 5 pg/mL and measurements below this limit are given a value of 5 pg/mL. The final visit for measurement estradiol concentrations occurred at a mean age +/- SD of 10.93 +/- 1.27 (range, 5.59 to 13.24) years. All females in the intent-to-treat (ITT) population and safety analysis set were identical for the treatment period. Study drug was discontinued at the initiation of puberty. N=subjects with evaluable data at given time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Mean Stimulated Testosterone Concentrations in Males | ||||||||||||||||||||||||||||
End point description |
Mean stimulated testosterone concentrations were assessed according to the DELFIA (registered trademark) assay. The final visit for measurement of testosterone occurred at a mean age +/- SD of 12.34 +/- 1.16 (range, 11.14 to 14.07) years. All males in the intent-to-treat (ITT) population and safety analysis set were identical for the treatment period. Study drug was discontinued at the initiation of puberty. N=subjects with evaluable data at given time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Mean Ratio of Bone Age to Chronological Age | ||||||||||||||||||||||||
End point description |
Bone age was determined by radiography of the wrist according to the Fels Method. The mean ratio of bone age to chronological age provides information about the slowing of bone age progression. A score = 1 indicates that bone age is equal to chronological age. The intent-to-treat (ITT) population and safety analysis set were identical for the treatment period. Study drug was discontinued at the initiation of puberty. N=subjects with evaluable data at given time point.
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End point type |
Secondary
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End point timeframe |
Week 24 and Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Posttreatment Height (ht.) Compared to Standard Population and as Predicted From Ht. at Baseline (BL) | ||||||||||||||||
End point description |
Height was measured by stadiometer and was standardized for age according to standard growth charts. A standardized score of 0 indicated a mean ht. equivalent to mean of a standard population from 2000 CDC standardized ht. charts. Height gain was calculated as ht. - predicted ht. from the Bayley-Pinneau method on the basis of bone age at baseline. Final adult ht. was determined by measurement at final adult ht., if available, or by ht. collected during the follow-up period associated with a growth velocity <1 cm/year or a bone age >14 yrs in females or >15 yrs in males. For the follow-up posttreatment period, the ITT population=40 subjects and the safety population=55 subjects who received at least 1 injection of study drug during the treatment period. Study drug was discontinued at the initiation of puberty. The mean age of subjects at final questionnaire completion was 24.76 years with a range of 18.87 to 26.66. N=subjects with evaluable data at given time point.
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End point type |
Other pre-specified
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End point timeframe |
Final ht. (measured or provided for final questionnaire in subjects >= 18 years of age) or near final adult ht. (<1 cm/year or bone age > 14 years for females or > 15 years for males)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Mean Time to or Mean Age at Regular Menses in Females After Treatment | ||||||||||||
End point description |
Regular menses was defined as 3 or more consecutive days of menstrual-like bleeding and was defined by the investigator's clinical judgment. During the posttreatment period, data were obtained from 32 female subjects. Twenty-seven subjects reported the start of menses, but only 26 subjects reported a menses start date.
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End point type |
Other pre-specified
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End point timeframe |
Posttreatment during the follow-up period (subjects observed every 6 months until physical and laboratory observations are at pubertal levels)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Female Subjects Who Reported Regular Menses at Adulthood | ||||||||||||
End point description |
Subjects were required to complete final adult questionnaire to provide information on adult reproductive function. Regular menses was defined as 3 or more consecutive days of menstrual-like bleeding. A long-term follow-up questionnaire was sent to all subjects who completed at least 1 visit in the posttreatment follow-up period or who discontinued treatment because they entered puberty naturally at the appropriate age. Twenty female subjects (mean age 24.76 years, range 18.87 to 26.66 years) and 0 male subjects completed the questionnaire.
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End point type |
Other pre-specified
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End point timeframe |
Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects Who Reported Pregnancies at Final Questionnaire | ||||||||||||
End point description |
The final questionnaire was completed by 20 females who were at least 18 years of age. The subjects reported on total number of pregnancies resulting in live births or number of miscarriages (spontaneous or elective) and whether the subject was currently pregnant. A long-term follow-up questionnaire was sent to all subjects who completed at least 1 visit in the posttreatment follow-up period or who discontinued treatment because they entered puberty naturally at the appropriate age. Twenty female subjects (mean age 24.76 years, range 18.87 to 26.66 years) and 0 male subjects completed the questionnaire.
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End point type |
Other pre-specified
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End point timeframe |
Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Pregnancies Reported by Subjects at Final Questionnaire | ||||||||||||||
End point description |
The final questionnaire was completed by 20 female subjects who were at least 18 years of age. The total number of pregnancies were reported. A long-term follow-up questionnaire was sent to all subjects who completed at least 1 visit in the posttreatment follow-up period or who discontinued treatment because they entered puberty naturally at the appropriate age. Twenty female subjects (mean age 24.76 years, range 18.87 to 26.66 years) and 0 male subjects completed the questionnaire.
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End point type |
Other pre-specified
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End point timeframe |
Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)
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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 |
Each investigator monitored each subject for clinical and laboratory evidence of adverse events at Weeks 4, 8, 12, 24, 36, 48, and then every 6 months until the study drug was discontinued.
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Adverse event reporting additional description |
Adverse events were reported from onset after the first injection of study drug through 30 days after treatment was completed. Treatment completion was defined as 28 days after the final study drug injection. The posttreatment follow-up period did not require the reporting of adverse events.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
COSTART | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
COSTART
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Reporting groups
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Reporting group title |
Leuprolide acetate 1 Month Depot
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Reporting group description |
Leuprolide acetate dosing was initiated at 300 mcg/kg (minimum dose 7.5 mg) administered intramuscularly (IM) every 28 days. Incremental adjustments to dosing at 3.75 mg increments were made at each visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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18 Aug 1993 |
● Incorporated the Phase 4 protocol |
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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. | |||
| Study drug was discontinued usually at the initiation of puberty (12 years for males and 11 years for females) with the concurrence of the investigator, or at the discretion of the investigator. Adverse events are coded with the COSTART dictionary. | |||
