A Study to Assess the Safety and Efficacy of Enantone (Leuprorelin) in Central Precocious Puberty (CPP) Among Chinese Participants

An Observational, Retrospective Study to Evaluate the Long Term Safety and Effectiveness of Leuprorelin in the Treatment of Central Precocious Puberty

The purpose of this study is to evaluate the long-term safety and efficacy of Enantone in the treatment of CPP in Chinese participants.

Study Overview

• Status: Completed
• Conditions: Central Precocious Puberty
• Intervention / Treatment: Drug: Enantone; Drug: GnRH agonist

Detailed Description

The drug being evaluated in this study is called Enantone (leuprorelin). Enantone is used to treat children who have CPP. This study will look at long term safety and efficacy of leuprorelin in the treatment of Chinese participants with CPP.

The study will enroll approximately 300 participants.

All participants who have received leuprorelin 30 mcg/kg to <90 mcg/kg or 90 mcg/kg to 180 mcg/kg per body weight, injection, subcutaneously, every 4 weeks up to at least 9 continuous months during the index period from September 1st 1998 to September 30th 2018 will be observed.

This multi-center trial will be conducted in China. Data will be collected over period of 20 months.

• Study Type: Observational
• Enrollment (Actual): 108

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • The Children's Hospital, Zhejiang University school of medicine
  • Hunan
    • Changsha, Hunan, China, 410007
      • Childrens Hospital of Hunan province
  • Jiangsu
    • Nanjing, Jiangsu, China, 210036
      • JiangSu Province Hosptial
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Children's Hospital of Jiangxi province
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Children's Hospital of Shanghai
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310053
      • The Children's Hospital, Zhejiang University school of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants diagnosed with CPP will be observed.

Description

Inclusion Criteria:

1. Has diagnosis of idiopathic CPP.
2. Has been treated with leuprorelin acetate (Enantone) for at least 9 continuous months of therapy with either a stable dose of high dose (greater than or equal to [>=] 90 mcg/kg up to 180 mcg/kg) or low dose (< 90 mcg/kg down to 30 mcg/kg).
3. Has initiated and completed treatment during the index period from September 1st 1998 to September 30th 2018.
4. Have the following information prior to initiation of enantone and at least one record of each of the following parameters at the end of enantone treatment in the medical records: Tanner staging, estradiol or testosterone level, and FSH and LH level. The participant should have at least one record of bone age prior to the initiation gonadotropin releasing hormone analogs (GnRHa) therapy with enantone to support the diagnosis of CPP. In addition, should have at least one record of bone age during treatment with enantone.

Exclusion Criteria:

1. Has been treated with leuprorelin acetate or any other GnRHa for conditions other than CPP.
2. Has used any other GnRHa products for CPP treatment prior to initiation of enantone therapy.
3. CPP participants with identified etiology, such as brain tumor or cranial irradiation.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment Phase: Enantone; Participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).	Drug: Enantone; Enantone suspension for injection; Other Names: Leuprorelin
Follow Up: Participants No longer Treated for CPP; Participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).
Follow Up: Treated with Non-Enantone GnRHa after Enantone; Participants who were continuing their CPP treatment with a non-Enantone gonadotropin releasing hormone agonist (GnRHa) after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).	Drug: GnRH agonist; A non-Enantone GnRH agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) During Enantone Treatment Phase	A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	During treatment with and up to 30 days post last dose of Enantone (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months)
Number of Participants With at Least One Treatment Emergent Adverse (TEAE) and Serious Adverse Event (SAE) During Follow-up Phase	A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Mean duration of follow-up=8.75 months (range: 1.9-29.5 months) for No longer treated for CPP group; 10.80 months (range: 2.8-20.5 months) for Treated with Non-Enantone GnRHa group after treatment with Enantone (while on another GnRHa)
Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Enantone Treatment Phase	Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.	The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months
Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Follow-Up Phase	Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.	No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase	The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.	The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months
Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase	The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.	No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone
Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase	Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.	The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months
Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase	Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.	No longer treated for CPP group-Month: 27 (766-855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group-Month 21 (586-675 days) post last dose of Enantone
Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Enantone Treatment Phase	Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.	The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months
Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Follow-up Phase	Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.	No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 18 (496-585 days) post last dose of Enantone

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2017
• Primary Completion (Actual): September 30, 2018
• Study Completion (Actual): September 30, 2018

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (Estimate): December 15, 2016

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: Leuprorelin-5001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No