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

Central Precocious Puberty Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01467882
• Other study ID #: Debio 8206-CPP-301
• Status: Completed
• Phase: Phase 3
• First received: November 7, 2011
• Last updated: July 27, 2017
• Start date: April 2012
• Est. completion date: July 2014

Study information

• Verified date: July 2017
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: July 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 9 Years

Eligibility

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 (?) 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).

Related Conditions & MeSH terms

• Central Precocious Puberty
• Puberty, Precocious

Intervention

Drug:
• Triptorelin
Powder and solution for solution for injection

Locations

Country	Name	City	State
Chile	IDIMI	Santiago
Mexico	Hospital Universitario de Monterrey	Monterrey
United States	Women's & Children's Hospital of Buffalo	Buffalo	New York
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Hackensack university medical center	Hackensack	New Jersey
United States	Lynn health Science Institute	Oklahoma City	Oklahoma
United States	Arnold Palmer Pediatric Endocrinology Practice	Orlando	Florida
United States	Pediatric Endocrinology of Phoenix	Phoenix	Arizona
United States	Washington University	Saint Louis	Missouri
United States	Children's National Medical Center	San Diego	California
United States	Swedish Pediatric Specialist	Seattle	Washington
United States	Nancy Wright MD P.A.	Tallahassee	Florida
United States	Children's National Medical Center	Washington, D.C.	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

United States,  Chile,  Mexico, 

References & 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. Review. — View 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. — View 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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	at Months 1, 2, 3, 9 and 12
Secondary	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.	from Month 6 to 12
Secondary	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.	at Months 1, 2, 3, 6, 9 and 12
Secondary	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.	from Month 6 to 12
Secondary	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
Secondary	Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12		Baseline to Months 1, 2, 3, 6, 9, and 12
Secondary	Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12		Baseline to Months 1, 2, 3, 6, 9, and 12
Secondary	Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12		at Months 1, 2, 3, 6, 9, and 12
Secondary	Percentage of Children Without Higher Basal LH and Estradiol or Testosterone		at 2 days after second triptorelin injection (Day 171)
Secondary	Change From Baseline in Height-for-age Z-score Per 2000 CDC Growth Charts at Months 6 and 12		Baseline to Months 6 and 12
Secondary	Change From Baseline in Height-for-age Percentile Per 2000 CDC Growth Charts at Months 6 and 12		Baseline to Months 6 and 12
Secondary	Change From Baseline in Growth Velocity at Months 6 and 12		Baseline to Months 6 and 12
Secondary	Percentage of Participants Without Bone Age / Chronological Age Ratio Increase From Baseline at Months 6 and 12		Baseline to Months 6 and 12
Secondary	Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12		at Months 6 and 12
Secondary	Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12		Baseline to Months 6 and 12
Secondary	Percentage of Boys With Absence of Progression of Testis Volumes Compared to Baseline at Months 6 and 12		Baseline to Months 6 and 12

External Links

•   Study sponsor