Back to resultsEfficacy, Safety, and Pharmacokinetics (PK) of Triptorelin 6-month Formulation in Patients With Central Precocious Puberty
Primary Purpose
Central Precocious Puberty
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Triptorelin
Sponsored by
About this trial
This is an interventional treatment trial for Central Precocious Puberty
Eligibility Criteria
Inclusion criteria:
- Onset of development of sex characteristics before 8 and 9 years in girls and boys, respectively (breast development in girls or testicular enlargement in boys according to the Tanner method), and candidate to receive at least 12 months of GnRH agonist therapy after study entry.
- Aged 2-8 years inclusive (i.e. < 9 years) for girls and 2-9 years inclusive (i.e. < 10 years) for boys at initiation of triptorelin treatment.
- Initiation of triptorelin treatment at the latest 18 months after onset of the first signs of precocious puberty.
- Difference (Δ) bone age (Greulich and Pyle method) - chronological age ≥ 1 year.
- Pubertal-type LH response 30 minutes following a GnRH agonist stimulation test before treatment initiation (leuprolide acetate 20 μg/kg SC) ≥ 6 IU/L.
- Clinical evidence of puberty, defined as Tanner Staging ≥ 2 for breast development for girls and testicular volume ≥ 4 mL (cc) for boys.
- 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.
Non-inclusion criteria:
- Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion.
- Non-progressing isolated premature thelarche.
- Presence of an unstable intracranial tumour or an intracranial tumour requiring neurosurgery or cerebral irradiation. Patients with hamartomas not requiring surgery are eligible.
- Evidence of renal (creatinine > 2 x ULN) or hepatic impairment (bilirubin or ASAT > 3 x ULN).
- Any other condition or chronic illness or treatment possibly interfering with growth or other study endpoints (e.g. chronic steroid use [except mild topical steroids], renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumour).
- Prior or current therapy with a GnRH agonist, medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF 1).
- Major medical or psychiatric illness that could interfere with study visits.
- Diagnosis of short stature, i.e. > 2.25 SD below the mean height for age.
- Positive pregnancy test.
- Known hypersensibility to any of the test materials or related compounds.
- Use of anticoagulants (heparin and coumarin derivatives).
Sites / Locations
- Pediatric Endocrinology of Phoenix
- Children's National Medical Center
- Children's National Medical Center
- Arnold Palmer Pediatric Endocrinology Practice
- Nancy Wright MD P.A.
- Washington University
- Hackensack university medical center
- Women's & Children's Hospital of Buffalo
- Cincinnati Children's Hospital
- Lynn health Science Institute
- Swedish Pediatric Specialist
- IDIMI
- Hospital Universitario de Monterrey
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Triptorelin
Arm Description
Triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Outcomes
Primary Outcome Measures
Percentage of Children With Luteinizing Hormone (LH) Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Month 6
This is a lab test to see what percentage of participants were returned to normal before-puberty levels at Month 6.
Secondary Outcome Measures
Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12
This is a lab test to see what percentage of children were returned to normal before-puberty levels by the drug at each time point.
Percentage of Children Maintaining LH Suppression at Prepubertal Levels 30 Minutes After Leuprolide Stimulation From Month 6 to 12
This is a lab test to see what percentage of children stayed at the normal before-puberty level from month 6 to month 12.
Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12
This is a lab test to see what percentage of children were returned to lower than normal before-puberty levels by the drug at each time point.
Percentage of Children Maintaining LH Suppression at </= 4 IU/L 30 Minutes After Leuprolide Stimulation From Month 6 to 12
This is a lab test to see what percentage of children stayed at the lower than normal before-puberty level from month 6 to month 12.
Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12
Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12
Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12
Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12
Percentage of Children Without Higher Basal LH and Estradiol or Testosterone
Change From Baseline in Height-for-age Z-score Per 2000 CDC Growth Charts at Months 6 and 12
Change From Baseline in Height-for-age Percentile Per 2000 CDC Growth Charts at Months 6 and 12
Change From Baseline in Growth Velocity at Months 6 and 12
Percentage of Participants Without Bone Age / Chronological Age Ratio Increase From Baseline at Months 6 and 12
Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12
Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12
Percentage of Boys With Absence of Progression of Testis Volumes Compared to Baseline at Months 6 and 12
Full Information
NCT ID
NCT01467882
First Posted
November 7, 2011
Last Updated
July 27, 2017
Sponsor
Debiopharm International SA
1. Study Identification
Unique Protocol Identification Number
NCT01467882
Brief Title
Efficacy, Safety, and Pharmacokinetics (PK) of Triptorelin 6-month Formulation in Patients With Central Precocious Puberty
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Debiopharm International SA
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study will investigate the efficacy, safety and pharmacokinetics of triptorelin 22.5 mg 6-month formulation in 44 patients suffering from central precocious puberty. The total study duration per patient will be 12 months (48 weeks).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Central Precocious Puberty
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Triptorelin
Arm Type
Experimental
Arm Description
Triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Intervention Type
Drug
Intervention Name(s)
Triptorelin
Other Intervention Name(s)
Trelstar
Intervention Description
Powder and solution for solution for injection
Primary Outcome Measure Information:
Title
Percentage of Children With Luteinizing Hormone (LH) Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Month 6
Description
This is a lab test to see what percentage of participants were returned to normal before-puberty levels at Month 6.
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12
Description
This is a lab test to see what percentage of children were returned to normal before-puberty levels by the drug at each time point.
Time Frame
at Months 1, 2, 3, 9 and 12
Title
Percentage of Children Maintaining LH Suppression at Prepubertal Levels 30 Minutes After Leuprolide Stimulation From Month 6 to 12
Description
This is a lab test to see what percentage of children stayed at the normal before-puberty level from month 6 to month 12.
Time Frame
from Month 6 to 12
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
Description
This is a lab test to see what percentage of children were returned to lower than normal before-puberty levels by the drug at each time point.
Time Frame
at Months 1, 2, 3, 6, 9 and 12
Title
Percentage of Children Maintaining LH Suppression at </= 4 IU/L 30 Minutes After Leuprolide Stimulation From Month 6 to 12
Description
This is a lab test to see what percentage of children stayed at the lower than normal before-puberty level from month 6 to month 12.
Time Frame
from Month 6 to 12
Title
Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12
Time Frame
Baseline to Months 1, 2, 3, 6, 9, and 12
Title
Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12
Time Frame
Baseline to Months 1, 2, 3, 6, 9, and 12
Title
Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12
Time Frame
Baseline to Months 1, 2, 3, 6, 9, and 12
Title
Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12
Time Frame
at Months 1, 2, 3, 6, 9, and 12
Title
Percentage of Children Without Higher Basal LH and Estradiol or Testosterone
Time Frame
at 2 days after second triptorelin injection (Day 171)
Title
Change From Baseline in Height-for-age Z-score Per 2000 CDC Growth Charts at Months 6 and 12
Time Frame
Baseline to Months 6 and 12
Title
Change From Baseline in Height-for-age Percentile Per 2000 CDC Growth Charts at Months 6 and 12
Time Frame
Baseline to Months 6 and 12
Title
Change From Baseline in Growth Velocity at Months 6 and 12
Time Frame
Baseline to Months 6 and 12
Title
Percentage of Participants Without Bone Age / Chronological Age Ratio Increase From Baseline at Months 6 and 12
Time Frame
Baseline to Months 6 and 12
Title
Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12
Time Frame
at Months 6 and 12
Title
Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12
Time Frame
Baseline to Months 6 and 12
Title
Percentage of Boys With Absence of Progression of Testis Volumes Compared to Baseline at Months 6 and 12
Time Frame
Baseline to Months 6 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
9 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Onset of development of sex characteristics before 8 and 9 years in girls and boys, respectively (breast development in girls or testicular enlargement in boys according to the Tanner method), and candidate to receive at least 12 months of GnRH agonist therapy after study entry.
Aged 2-8 years inclusive (i.e. < 9 years) for girls and 2-9 years inclusive (i.e. < 10 years) for boys at initiation of triptorelin treatment.
Initiation of triptorelin treatment at the latest 18 months after onset of the first signs of precocious puberty.
Difference (Δ) bone age (Greulich and Pyle method) - chronological age ≥ 1 year.
Pubertal-type LH response 30 minutes following a GnRH agonist stimulation test before treatment initiation (leuprolide acetate 20 μg/kg SC) ≥ 6 IU/L.
Clinical evidence of puberty, defined as Tanner Staging ≥ 2 for breast development for girls and testicular volume ≥ 4 mL (cc) for boys.
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.
Non-inclusion criteria:
Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion.
Non-progressing isolated premature thelarche.
Presence of an unstable intracranial tumour or an intracranial tumour requiring neurosurgery or cerebral irradiation. Patients with hamartomas not requiring surgery are eligible.
Evidence of renal (creatinine > 2 x ULN) or hepatic impairment (bilirubin or ASAT > 3 x ULN).
Any other condition or chronic illness or treatment possibly interfering with growth or other study endpoints (e.g. chronic steroid use [except mild topical steroids], renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumour).
Prior or current therapy with a GnRH agonist, medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF 1).
Major medical or psychiatric illness that could interfere with study visits.
Diagnosis of short stature, i.e. > 2.25 SD below the mean height for age.
Positive pregnancy test.
Known hypersensibility to any of the test materials or related compounds.
Use of anticoagulants (heparin and coumarin derivatives).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tala Dajani, MD
Organizational Affiliation
Pediatric Endocrinology of Phoenix, Arizona
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barry Reiner, MD
Organizational Affiliation
Barry J. Reiner, MD, LLC, Baltimore, Maryland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Galal Salem, MD
Organizational Affiliation
SRCR, Inc, Bell Gardens, California
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Heidi Shea, MD
Organizational Affiliation
Endocrine Associates of Dallas, Plano, Texas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark Rappaport, MD
Organizational Affiliation
Pediatric Endocrine Associates, Atlanta, Georgia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Opada Alzohaili, MD
Organizational Affiliation
Alzohaili Medical Consultants, Dearborn, Michigan
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Quentin Van Meter, MD
Organizational Affiliation
Van Meter Pediatric Endocrinology, Peachtree City, Georgia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Domek, MD
Organizational Affiliation
Lynn health Science Institute, Oklahoma City
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kathleen Bethin, MD
Organizational Affiliation
Women's & Children's Hospital of Buffalo, New York
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Kaplowitz, MD
Organizational Affiliation
Children's National Medical Center, Washington
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Karen Klein, MD
Organizational Affiliation
Children's National Medical Center, San Diego, California
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Diane Merritt, MD
Organizational Affiliation
Washington University, St. Louis, Missouri
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Susan Rose, MD
Organizational Affiliation
Cincinnati Children's Hospital, Ohio
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gad Kletter, MD
Organizational Affiliation
Swedish Pediatric Specialist, Seattle, Washington
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Javier Aisenberg, MD
Organizational Affiliation
Hackensack university medical center, New Jersey
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dennis Brenner, MD
Organizational Affiliation
St. Barnabas Medical Center, Livingston, New Jersey
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Douglas Rogers, MD
Organizational Affiliation
Cleveland Clinic, Ohio
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lawrence Silverman, MD
Organizational Affiliation
Goryeb Children's Hospital, Morristown, New Jersey
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Lee, MD
Organizational Affiliation
Penn State Hershey Children's Hospital, Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ricardo Gomez, MD
Organizational Affiliation
Children's Hospital, New Orleans, Louisiana
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fernando Cassorla, MD
Organizational Affiliation
IDIMI, Santiago, Chile
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joshua Yang, MD
Organizational Affiliation
Arnold Palmer Pediatric Endocrinology Practice, Orlando, Florida
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Erica Eugster, MD
Organizational Affiliation
James Whitcomb Riley Hospital for Children, Indianapolis, Indiana
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Oscar Flores, MD
Organizational Affiliation
Hospital Universitario de Monterrey, Mexico
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nancy Wright, MD
Organizational Affiliation
Nancy Wright MD P.A., Tallahasse, Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pediatric Endocrinology of Phoenix
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85053
Country
United States
Facility Name
Children's National Medical Center
City
San Diego
State/Province
California
Country
United States
Facility Name
Children's National Medical Center
City
Washington, D.C.
State/Province
District of Columbia
Country
United States
Facility Name
Arnold Palmer Pediatric Endocrinology Practice
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Nancy Wright MD P.A.
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Hackensack university medical center
City
Hackensack
State/Province
New Jersey
Country
United States
Facility Name
Women's & Children's Hospital of Buffalo
City
Buffalo
State/Province
New York
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Lynn health Science Institute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Swedish Pediatric Specialist
City
Seattle
State/Province
Washington
Country
United States
Facility Name
IDIMI
City
Santiago
Country
Chile
Facility Name
Hospital Universitario de Monterrey
City
Monterrey
Country
Mexico
12. IPD Sharing Statement
Citations:
PubMed Identifier
19332438
Citation
Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR; ESPE-LWPES GnRH Analogs Consensus Conference Group; Antoniazzi F, Berenbaum S, Bourguignon JP, Chrousos GP, Coste J, Deal S, de Vries L, Foster C, Heger S, Holland J, Jahnukainen K, Juul A, Kaplowitz P, Lahlou N, Lee MM, Lee P, Merke DP, Neely EK, Oostdijk W, Phillip M, Rosenfield RL, Shulman D, Styne D, Tauber M, Wit JM. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009 Apr;123(4):e752-62. doi: 10.1542/peds.2008-1783. Epub 2009 Mar 30.
Results Reference
background
PubMed Identifier
16995580
Citation
Martinez-Aguayo A, Hernandez MI, Beas F, Iniguez G, Avila A, Sovino H, Bravo E, Cassorla F. Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation. J Pediatr Endocrinol Metab. 2006 Aug;19(8):963-70. doi: 10.1515/jpem.2006.19.8.963.
Results Reference
background
PubMed Identifier
19189683
Citation
Houk CP, Kunselman AR, Lee PA. The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-minute post-stimulation LH sample is adequate. J Pediatr Endocrinol Metab. 2008 Dec;21(12):1113-8. doi: 10.1515/jpem.2008.21.12.1113.
Results Reference
background
PubMed Identifier
10969915
Citation
Lahlou N, Carel JC, Chaussain JL, Roger M. Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics. J Pediatr Endocrinol Metab. 2000 Jul;13 Suppl 1:723-37. doi: 10.1515/jpem.2000.13.s1.723.
Results Reference
background
Links:
URL
http://www.debiopharm.com
Description
Study sponsor
Learn more about this trial
Efficacy, Safety, and Pharmacokinetics (PK) of Triptorelin 6-month Formulation in Patients With Central Precocious Puberty
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