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

NCT01467882 | Completed Phase 3 Results

• 1 other identifier: Debio 8206-CPP-301
• Study Type: interventional
• Target: 44
• Locations: 3 countries
• Sites: 13

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).

Conditions

Central Precocious Puberty

Outcome Measures

Primary Outcomes (1)

• 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.

  Month 6

Secondary Outcomes (16)

• Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12

  at Months 1, 2, 3, 9 and 12

• Percentage of Children Maintaining LH Suppression at Prepubertal Levels 30 Minutes After Leuprolide Stimulation From Month 6 to 12

  from Month 6 to 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

  at Months 1, 2, 3, 6, 9 and 12

• Percentage of Children Maintaining LH Suppression at </= 4 IU/L 30 Minutes After Leuprolide Stimulation From Month 6 to 12

  from Month 6 to 12

• Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12

  Baseline to Months 1, 2, 3, 6, 9, and 12

Study Arms (1)

Triptorelin

EXPERIMENTAL

Triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169

Drug: Triptorelin

Interventions

Triptorelin DRUG

Powder and solution for solution for injection

Also known as: Trelstar

Triptorelin

Eligibility Criteria

• Age: 2 Years - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (13)

Pediatric Endocrinology of Phoenix

Phoenix, Arizona, 85053, United States

Location

Children's National Medical Center

San Diego, California, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, United States

Location

Arnold Palmer Pediatric Endocrinology Practice

Orlando, Florida, United States

Location

Nancy Wright MD P.A.

Tallahassee, Florida, 32308, United States

Location

Washington University

St Louis, Missouri, United States

Location

Hackensack university medical center

Hackensack, New Jersey, United States

Location

Women's & Children's Hospital of Buffalo

Buffalo, New York, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Location

Lynn health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Swedish Pediatric Specialist

Seattle, Washington, United States

Location

IDIMI

Santiago, Chile

Location

Hospital Universitario de Monterrey

Monterrey, Mexico

Location

Related Publications (4)

• 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.

  PMID: 19332438 BACKGROUND

• 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.

  PMID: 16995580 BACKGROUND

• 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.

  PMID: 19189683 BACKGROUND

• 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.

  PMID: 10969915 BACKGROUND

Related Links

• Study sponsor

MeSH Terms

Conditions

Puberty, Precocious

Interventions

Triptorelin Pamoate

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Eija Lundström
• Organization: Debiopharm International, S.A.

eija.lundstrom@debiopharm.com

:+41 21 3210111

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2011
• First Posted: November 9, 2011
• Study Start: April 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: July 1, 2014
• Last Updated: July 28, 2017
• Results First Posted: September 4, 2015

Record last verified: 2017-07

Locations

US (11); ME (1); CL (1)