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

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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).

Condition or disease	Intervention/treatment	Phase
Central Precocious Puberty	Drug: Triptorelin	Phase 3

Study Design

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	44 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	April 2012
Actual Primary Completion Date :	August 2013
Actual Study Completion Date :	July 2014

Arms and Interventions

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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

Outcome Measures

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Percentage of Children With Luteinizing Hormone (LH) Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Month 6 [ Time Frame: 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 :

1. 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 ]
   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.
2. 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 ]
   This is a lab test to see what percentage of children stayed at the normal before-puberty level from month 6 to month 12.
3. 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 ]
   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.
4. 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 ]
   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.
5. 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 ]
6. 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 ]
7. 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 ]
8. 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 ]
9. Percentage of Children Without Higher Basal LH and Estradiol or Testosterone [ Time Frame: at 2 days after second triptorelin injection (Day 171) ]
10. 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 ]
11. 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 ]
12. Change From Baseline in Growth Velocity at Months 6 and 12 [ Time Frame: Baseline to Months 6 and 12 ]
13. 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 ]
14. Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12 [ Time Frame: at Months 6 and 12 ]
15. Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12 [ Time Frame: Baseline to Months 6 and 12 ]
16. 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 ]

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	2 Years to 9 Years (Child)
Sexes Eligible for Study:	All
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

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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, D.C., District of Columbia, United States
United States, Florida
Arnold Palmer Pediatric Endocrinology Practice
Orlando, Florida, United States
Nancy Wright MD P.A.
Tallahassee, Florida, United States, 32308
United States, Missouri
Washington University
Saint 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

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Study sponsor 

Publications:

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. Review.

Martínez-Aguayo A, Hernández MI, Beas F, Iñiguez 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.

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.

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. Review.

Responsible Party:	Debiopharm International SA
ClinicalTrials.gov Identifier:	NCT01467882 History of Changes
Other Study ID Numbers:	Debio 8206-CPP-301
First Posted:	November 9, 2011
Results First Posted:	September 4, 2015
Last Update Posted:	July 28, 2017
Last Verified:	July 2017

Additional relevant MeSH terms:

Puberty, Precocious; Gonadal Disorders; Endocrine System Diseases; Triptorelin Pamoate; Luteolytic Agents; Contraceptive Agents, Female	Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents