A Phase 3, Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy and Safety of Leuprolide Acetate 11.25 and 30 mg Formulations in Children With Central Precocious Puberty
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Abbott
- 入组人数
- 84
- 试验地点
- 25
- 主要终点
- Percentage of Participants With Suppression of Peak Stimulated Luteinizing Hormone (<4 mIU/mL) From Month 2 Through Month 6
研究概览
简要总结
The purpose of this study is to determine if 11.25 and 30 mg formulations of leuprolide are effective in treating children with Central Precocious Puberty (CPP).
详细描述
Study Design:
A total of 80 children with confirmed CPP were planned to be enrolled and randomized in a 1:1 ratio to receive 2 injections of either leuprolide acetate 11.25 mg or 30 mg depot formulation, each injection administered 3 mo apart (6 mo of treatment):
This study includes a 4-week Screening Period, two 3-mo treatment cycles, and a posttreatment follow-up period (12 weeks following the Mo 6 visit). Study visits will occur at Screening, Day 1, Week 2 (only for subjects participating in the pharmacokinetic subset), Mo 1, 2, 3, Mo 6/Early Termination, and 12 weeks later, for the Posttreatment Follow-up Visit.
This study was conducted at 18 sites in the United States and 4 sites in Puerto Rico.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has a clinical diagnosis of CPP.
- •Eligible to receive at least 6 mo of therapy to treat CPP after study entry.
- •Bone age advanced at least 1 year beyond the chronological age at time of diagnosis or first treatment.
- •In general good health with no uncontrolled, clinically significant disease which would interfere with bone maturation or mask the objectives of this protocol as assessed by the investigator.
- •Additional criteria for subjects who have not had previous treatment:
- •Girls 2-8 years inclusive or Boys 2-9 years inclusive at Day
- •Has pretreatment pubertal response to leuprolide acetate stimulation (luteinizing hormone ≥8 mIU/mL) at Screening.
- •Breast pubertal staging of at least 2 in girls; testicular volume of at least 4 cc or testicular length greater than 2.5 cm in boys at Screening.
- •Additional criteria for subjects previously treated:
- •Girls 2-10 years inclusive or boys 2-11 years inclusive at Day
- •Must have been on standard gonadotropin releasing hormone analog therapy for at least the 6 mo prior to Day
- •Has documented maintenance of luteinizing hormone suppression as evidenced by peak stimulated level <4 mIU/mL at Screening.
排除标准
- •Incomplete precocious puberty (premature thelarche, premature adrenarche).
- •Peripheral precocious puberty: gonadal or adrenal tumors, congenital adrenal hyperplasia, testotoxicosis in boys, human chorionic gonadotropin secreting tumor or McCune-Albright syndrome in girls.
- •Evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid and gonadal function other than premature secretion of gonadotropins not adequately controlled.
- •Unstable intracranial tumors (unresponsive to treatment/expanding) except hamartoma.
- •Previous treatment with GnRHa therapy requiring leuprolide acetate for depot suspension >15 mg monthly.
- •Bone age >13 years for girls and >14 years for boys.
- •Any other condition interfering with growth, ie, skeletal dysplasia, cerebral palsy.
- •Chronic illness requiring treatment that may interfere with growth, ie, chronic steroid use, renal failure, moderate to severe scoliosis.
- •Diagnosis of short stature, ie more than 2.25 standard deviations below the mean height for age (growth chart measurement).
- •Prior or current therapy with medroxyprogesterone acetate or growth hormone.
- •Has an abnormal laboratory value suggesting a clinically significant underlying disease .
- •Creatinine >1.5 mg/dL, alanine aminotransferase and/or aspartate aminotransferase >2.0 x upper limit of normal, or total bilirubin >2.0 mg/dL with aspartate aminotransferase/alanine aminotransferase elevated above normal limits.
- •Positive pregnancy test.
- •Known hypersensitivity to study medication or its excipients.
- •Participation in another drug research within 3 mo of enrollment into this study.
- •Prior or current therapy with insulin-like growth factor-
- •Use of an estrogen preparation within 2 mo prior to Day 1.
研究组 & 干预措施
Leuprolide acetate 11.25 mg
There are 2 arms that received leuprolide acetate 11.25 mg. Subjects who are treatment naive to leuprolide acetate are designated to be in Arm A and subjects who have previously been treated with leuprolide acetate are designated to be in Arm B.
干预措施: Leuprolide acetate 11.25 mg (Drug)
Leuprolide acetate 30 mg
There are 2 arms that received leuprolide acetate 30 mg. Subjects who are treatment naive to leuprolide acetate are designated to be in Arm C and subjects who have previously been treated with leuprolide acetate are designated to be in Arm D.
干预措施: Leuprolide acetate 30 mg (Drug)
结局指标
主要结局
Percentage of Participants With Suppression of Peak Stimulated Luteinizing Hormone (<4 mIU/mL) From Month 2 Through Month 6
时间窗: Month 2 through 6
Percentage of participants with suppression of peak stimulated luteinizing hormone that was measured after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test at Month (Mo) 2, 3, and 6. The analysis was performed according to a life table method. Subjects who withdrew without peak-stimulated luteinizing hormone \>= 4 mIU/mL were censored at their last measurement of peak-stimulated luteinizing hormone.
次要结局
- Percentage of Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) at Month 6(Month 6)
- Percentage of Participants With Suppression of Basal Estradiol <20 pg/mL by Visit(Month 1, 2, 3 and 6)
- Percentage of Participants With Suppression of Testosterone in <30 ng/dL by Visit(Month 1, 2, 3 and 6)
- Peak-stimulated Luteinizing Hormone Concentration by Visit(Baseline, Month 1, 2, 3 and 6)
- Percentage of Participants With Suppression of the Physical Signs of Puberty (Breast Development) at Month 6(Month 6)
- Change From Baseline in Incremental Growth Rate (cm/Year) at Month 6(Baseline and Month 6)
- Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age at Month 6(Baseline to Month 6)