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

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ClinicalTrials.gov Identifier: NCT02993926
Recruitment Status : Completed
First Posted : December 15, 2016
Results First Posted : October 24, 2019
Last Update Posted : October 24, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

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

Condition or disease Intervention/treatment
Puberty, Central Precocious 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.

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Study Type : Observational
Actual Enrollment : 108 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: An Observational, Retrospective Study to Evaluate the Long Term Safety and Effectiveness of Leuprorelin in the Treatment of Central Precocious Puberty
Actual Study Start Date : June 24, 2017
Actual Primary Completion Date : September 30, 2018
Actual Study Completion Date : September 30, 2018


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 Name: 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




Primary Outcome Measures :
  1. Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) During Enantone Treatment Phase [ Time Frame: 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) ]
    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.

  2. Number of Participants With at Least One Treatment Emergent Adverse (TEAE) and Serious Adverse Event (SAE) During Follow-up Phase [ Time Frame: 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) ]
    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.

  3. Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Enantone Treatment Phase [ Time Frame: The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months ]
    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.

  4. Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Follow-Up Phase [ Time Frame: 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 ]
    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months ]
    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.

  2. 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 [ Time Frame: 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 ]
    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.

  3. Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase [ Time Frame: The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months ]
    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.

  4. Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase [ Time Frame: 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 ]
    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.

  5. Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Enantone Treatment Phase [ Time Frame: The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months ]
    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.

  6. Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Follow-up Phase [ Time Frame: 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 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants diagnosed with CPP will be observed.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02993926


Locations
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China, Hubei
The Children's Hospital, Zhejiang University School of Medicine
Wuhan, Hubei, China, 430030
China, Hunan
Childrens Hospital of Hunan province
Changsha, Hunan, China, 410007
China, Jiangsu
Jiangsu Province Hosptial
Nanjing, Jiangsu, China, 210036
China, Jiangxi
Children's Hospital of Jiangxi province
Nanchang, Jiangxi, China, 330006
China, Shanghai
Children's Hospital of Shanghai
Shanghai, Shanghai, China, 200040
China, Zhejiang
The Children's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China, 310053
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director Clinical Science Takeda
  Study Documents (Full-Text)

Documents provided by Takeda:
Statistical Analysis Plan  [PDF] January 22, 2019
Study Protocol  [PDF] January 26, 2018

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02993926    
Other Study ID Numbers: Leuprorelin-5001
First Posted: December 15, 2016    Key Record Dates
Results First Posted: October 24, 2019
Last Update Posted: October 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
Drug Therapy
Additional relevant MeSH terms:
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Puberty, Precocious
Gonadal Disorders
Endocrine System Diseases
Leuprolide
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents