Efficacy, Safety, and Pharmacokinetics (PK) of Triptorelin 6-month Formulation in Patients With Central Precocious Puberty

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT01467882
First received: November 7, 2011
Last updated: August 5, 2015
Last verified: August 2015
  Purpose

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).


Condition Intervention Phase
Central Precocious Puberty
Drug: Triptorelin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • Percentage of Children With Luteinizing Hormone (LH) Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: at Months 1, 2, 3, 9 and 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: from Month 6 to 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: at Months 1, 2, 3, 6, 9 and 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: from Month 6 to 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Months 1, 2, 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percentage of Children Without Higher Basal LH and Estradiol or Testosterone [ Time Frame: at 2 days after second triptorelin injection (Day 171) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change From Baseline in Growth Velocity at Months 6 and 12 [ Time Frame: Baseline to Months 6 and 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12 [ Time Frame: at Months 6 and 12 ] [ Designated as safety issue: No ]
  • Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12 [ Time Frame: Baseline to Months 6 and 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: April 2012
Study Completion Date: July 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Triptorelin
Triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169
Drug: Triptorelin
Powder and solution for solution for injection
Other Name: Trelstar

  Eligibility

Ages Eligible for Study:   2 Years to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. 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.
  2. 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.
  3. Initiation of triptorelin treatment at the latest 18 months after onset of the first signs of precocious puberty.
  4. Difference (Δ) bone age (Greulich and Pyle method) - chronological age ≥ 1 year.
  5. Pubertal-type LH response 30 minutes following a GnRH agonist stimulation test before treatment initiation (leuprolide acetate 20 μg/kg SC) ≥ 6 IU/L.
  6. Clinical evidence of puberty, defined as Tanner Staging ≥ 2 for breast development for girls and testicular volume ≥ 4 mL (cc) for boys.
  7. 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:

  1. Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion.
  2. Non-progressing isolated premature thelarche.
  3. Presence of an unstable intracranial tumour or an intracranial tumour requiring neurosurgery or cerebral irradiation. Patients with hamartomas not requiring surgery are eligible.
  4. Evidence of renal (creatinine > 2 x ULN) or hepatic impairment (bilirubin or ASAT > 3 x ULN).
  5. 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).
  6. Prior or current therapy with a GnRH agonist, medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF 1).
  7. Major medical or psychiatric illness that could interfere with study visits.
  8. Diagnosis of short stature, i.e. > 2.25 SD below the mean height for age.
  9. Positive pregnancy test.
  10. Known hypersensibility to any of the test materials or related compounds.
  11. Use of anticoagulants (heparin and coumarin derivatives).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01467882

Locations
United States, Arizona
Pediatric Endocrinology of Phoenix
Phoenix, Arizona, United States, 85053
United States, California
Children's National Medical Center
San Diego, California, United States
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States
United States, Florida
Arnold Palmer Pediatric Endocrinology Practice
Orlando, Florida, United States
Nancy Wright MD P.A.
Tallahasse, Florida, United States, 32308
United States, Missouri
Washington University
St. Louis, Missouri, United States
United States, New Jersey
Hackensack university medical center
Hackensack, New Jersey, United States
United States, New York
Women's & Children's Hospital of Buffalo
Buffalo, New York, United States
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
United States, Oklahoma
Lynn health Science Institute
Oklahoma City, Oklahoma, United States, 73112
United States, Washington
Swedish Pediatric Specialist
Seattle, Washington, United States
Chile
IDIMI
Santiago, Chile
Mexico
Hospital Universitario de Monterrey
Monterrey, Mexico
Sponsors and Collaborators
Debiopharm International SA
Investigators
Principal Investigator: Tala Dajani, MD Pediatric Endocrinology of Phoenix, Arizona
Principal Investigator: Barry Reiner, MD Barry J. Reiner, MD, LLC, Baltimore, Maryland
Principal Investigator: Galal Salem, MD SRCR, Inc, Bell Gardens, California
Principal Investigator: Heidi Shea, MD Endocrine Associates of Dallas, Plano, Texas
Principal Investigator: Mark Rappaport, MD Pediatric Endocrine Associates, Atlanta, Georgia
Principal Investigator: Opada Alzohaili, MD Alzohaili Medical Consultants, Dearborn, Michigan
Principal Investigator: Quentin Van Meter, MD Van Meter Pediatric Endocrinology, Peachtree City, Georgia
Principal Investigator: David Domek, MD Lynn health Science Institute, Oklahoma City
Principal Investigator: Kathleen Bethin, MD Women's & Children's Hospital of Buffalo, New York
Principal Investigator: Paul Kaplowitz, MD Children's National Medical Center, Washington
Principal Investigator: Karen Klein, MD Children's National Medical Center, San Diego, California
Principal Investigator: Diane Merritt, MD Washington University, St. Louis, Missouri
Principal Investigator: Susan Rose, MD Cincinnati Children's Hospital, Ohio
Principal Investigator: Gad Kletter, MD Swedish Pediatric Specialist, Seattle, Washington
Principal Investigator: Javier Aisenberg, MD Hackensack university medical center, New Jersey
Principal Investigator: Dennis Brenner, MD St. Barnabas Medical Center, Livingston, New Jersey
Principal Investigator: Douglas Rogers, MD Cleveland Clinic, Ohio
Principal Investigator: Lawrence Silverman, MD Goryeb Children's Hospital, Morristown, New Jersey
Principal Investigator: Peter Lee, MD Penn State Hershey Children's Hospital, Pennsylvania
Principal Investigator: Ricardo Gomez, MD Children's Hospital, New Orleans, Louisiana
Principal Investigator: Fernando Cassorla, MD IDIMI, Santiago, Chile
Principal Investigator: Joshua Yang, MD Arnold Palmer Pediatric Endocrinology Practice, Orlando, Florida
Principal Investigator: Erica Eugster, MD James Whitcomb Riley Hospital for Children, Indianapolis, Indiana
Principal Investigator: Oscar Flores, MD Hospital Universitario de Monterrey, Mexico
Principal Investigator: Nancy Wright, MD Nancy Wright MD P.A., Tallahasse, Florida
  More Information

Additional Information:
Publications:
Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT01467882     History of Changes
Other Study ID Numbers: Debio 8206-CPP-301
Study First Received: November 7, 2011
Results First Received: June 25, 2015
Last Updated: August 5, 2015
Health Authority: United States: Food and Drug Administration
Chile: Instituto de Salud Pública de Chile
Mexico: Secretaria de Salud

Additional relevant MeSH terms:
Puberty, Precocious
Endocrine System Diseases
Gonadal Disorders
Triptorelin Pamoate
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Contraceptive Agents
Contraceptive Agents, Female
Luteolytic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 03, 2015