Clinical trial NCT01467882: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Central Precocious Puberty
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2011-11-09
Enrollment: 44
Sex: ALL
Minimum age (years): 2
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility 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).

Primary outcomes:
measure: Percentage of Children With Luteinizing Hormone (LH) Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Month 6
timeFrame: Month 6
Secondary outcomes:
measure: Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12
timeFrame: at Months 1, 2, 3, 9 and 12
measure: Percentage of Children Maintaining LH Suppression at Prepubertal Levels 30 Minutes After Leuprolide Stimulation From Month 6 to 12
timeFrame: from Month 6 to 12
measure: Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12
timeFrame: at Months 1, 2, 3, 6, 9 and 12
measure: Percentage of Children Maintaining LH Suppression at </= 4 IU/L 30 Minutes After Leuprolide Stimulation From Month 6 to 12
timeFrame: from Month 6 to 12
measure: Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12
timeFrame: Baseline to Months 1, 2, 3, 6, 9, and 12
measure: Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12
timeFrame: Baseline to Months 1, 2, 3, 6, 9, and 12
measure: Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12
timeFrame: Baseline to Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12
timeFrame: at Months 1, 2, 3, 6, 9, and 12
measure: Percentage of Children Without Higher Basal LH and Estradiol or Testosterone
timeFrame: at 2 days after second triptorelin injection (Day 171)
measure: Change From Baseline in Height-for-age Z-score Per 2000 CDC Growth Charts at Months 6 and 12
timeFrame: Baseline to Months 6 and 12
measure: Change From Baseline in Height-for-age Percentile Per 2000 CDC Growth Charts at Months 6 and 12
timeFrame: Baseline to Months 6 and 12
measure: Change From Baseline in Growth Velocity at Months 6 and 12
timeFrame: Baseline to Months 6 and 12
measure: Percentage of Participants Without Bone Age / Chronological Age Ratio Increase From Baseline at Months 6 and 12
timeFrame: Baseline to Months 6 and 12
measure: Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12
timeFrame: at Months 6 and 12
measure: Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12
timeFrame: Baseline to Months 6 and 12
measure: Percentage of Boys With Absence of Progression of Testis Volumes Compared to Baseline at Months 6 and 12
timeFrame: Baseline to Months 6 and 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pediatric Endocrinology of Phoenix
state: Arizona
city: San Diego
country: United States
facility: Children's National Medical Center
state: California
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Orlando
country: United States
facility: Arnold Palmer Pediatric Endocrinology Practice
state: Florida
city: Tallahassee
country: United States
facility: Nancy Wright MD P.A.
state: Florida
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Hackensack
country: United States
facility: Hackensack university medical center
state: New Jersey
city: Buffalo
country: United States
facility: Women's & Children's Hospital of Buffalo
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn health Science Institute
state: Oklahoma
city: Seattle
country: United States
facility: Swedish Pediatric Specialist
state: Washington
city: Santiago
country: Chile
facility: IDIMI
city: Monterrey
country: Mexico
facility: Hospital Universitario de Monterrey
Study officials:
affiliation: Pediatric Endocrinology of Phoenix, Arizona
name: Tala Dajani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Barry J. Reiner, MD, LLC, Baltimore, Maryland
name: Barry Reiner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SRCR, Inc, Bell Gardens, California
name: Galal Salem, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Endocrine Associates of Dallas, Plano, Texas
name: Heidi Shea, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pediatric Endocrine Associates, Atlanta, Georgia
name: Mark Rappaport, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Alzohaili Medical Consultants, Dearborn, Michigan
name: Opada Alzohaili, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Van Meter Pediatric Endocrinology, Peachtree City, Georgia
name: Quentin Van Meter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lynn health Science Institute, Oklahoma City
name: David Domek, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Women's & Children's Hospital of Buffalo, New York
name: Kathleen Bethin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's National Medical Center, Washington
name: Paul Kaplowitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's National Medical Center, San Diego, California
name: Karen Klein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University, St. Louis, Missouri
name: Diane Merritt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cincinnati Children's Hospital, Ohio
name: Susan Rose, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swedish Pediatric Specialist, Seattle, Washington
name: Gad Kletter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hackensack university medical center, New Jersey
name: Javier Aisenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Barnabas Medical Center, Livingston, New Jersey
name: Dennis Brenner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cleveland Clinic, Ohio
name: Douglas Rogers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Goryeb Children's Hospital, Morristown, New Jersey
name: Lawrence Silverman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Penn State Hershey Children's Hospital, Pennsylvania
name: Peter Lee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital, New Orleans, Louisiana
name: Ricardo Gomez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IDIMI, Santiago, Chile
name: Fernando Cassorla, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arnold Palmer Pediatric Endocrinology Practice, Orlando, Florida
name: Joshua Yang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: James Whitcomb Riley Hospital for Children, Indianapolis, Indiana
name: Erica Eugster, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de Monterrey, Mexico
name: Oscar Flores, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nancy Wright MD P.A., Tallahasse, Florida
name: Nancy Wright, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.