Pharmacokinetic Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty

Central Precocious Puberty Clinical Trial

Official title:

An Open-label, Single Arm, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Leuprolide Acetate 45 mg for Injectable Suspension Controlled Release in Subjects With Central (Gonadotropin-Dependent) Precocious Puberty—Part A and B

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02811471
• Other study ID #: 611
• Status: Recruiting
• Phase: Phase 3
• First received: June 21, 2016
• Last updated: June 21, 2016
• Start date: June 2016
• Est. completion date: July 2018

Study information

• Verified date: June 2016
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Exploring the efficacy in Leuprolide 45mg in slowing down or reversing Central Precocious Puberty in girls ages 2-8 and boys ages 2-9.

Description:

Primary Objectives Determine the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with CPP.

Secondary Objectives

• Evaluate the safety and tolerability of leuprolide acetate 45 mg for injectable suspension in children with CPP

• Characterize the burst kinetics of leuprolide acetate 45 mg after the first administration

• Characterize the pharmacodynamic (PD) relationship of leuprolide serum concentrations to concentrations of serum LH, FSH and to testosterone/estradiol

• Assess percent changes in height velocity and bone age progression after the first administration

• Assess changes in physical signs of puberty as measured by changes in Tanner stages or in changes or onset of menses

• Determine the dosing interval (5 or 6 months) at which leuprolide acetate is able to suppress LH concentration to <4 mIU/mL (after GnRHa stimulation test), as data permit

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: July 2018
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 9 Years

Eligibility

Inclusion Criteria:

1. Females age 2 to 8 years (inclusive) or males age 2 to 9 years (inclusive)

2. Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRH agonist treatment for CPP

3. Pubertal-type LH response following an abbreviated GnRHa stimulation test before treatment initiation > 5 mIU/mL

4. Clinical evidence of puberty, defined as Tanner stage = 2 for breast development in females or testicular volume = 4 mL in males

5. Willing and able to participate in the study

6. Difference between bone age (Greulich and Pyle method) and chronological age = 1 year

7. Signed Institutional Review Board/Independent Ethics Committee (IRB/IEC)-approved informed consent form (ICF) by one or both parents (per IRB/IEC requirements), by the custodial parent or by the legal guardian(s) (if required)

8. Signed Assent by subjects as per IRB/IEC requirements

Exclusion Criteria:

1. Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion

2. Prior or current GnRH treatment for CPP

3. Non-progressing isolated premature thelarche

4. Presence of an unstable intracranial tumor or an intracranial tumor requiring neurosurgery or cerebral irradiation. Subjects with hamartomas not requiring surgery are eligible.

5. Any other condition, chronic illness or treatment that, in the opinion of the Investigator, may interfere with growth or other study endpoints (eg, chronic steroid use [except mild topical steroids) renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor).

6. Prior or current therapy with 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 (ie, 2.25 standard deviations (SD) below the mean height for age)

9. Positive urine pregnancy test

10. Known hypersensitivity to GnRH or related compounds

11. Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study

12. Any other condition(s) which could significantly interfere with Protocol compliance

13. Treatment with an investigational product within 5 half-lives of that product in prior clinical studies before the baseline visit (Day 0)

14. Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions

15. Prior (within 6 months of Baseline (Day 0)) or current use of medications that, per Investigator opinion, have been associated with seizures or convulsions

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Central Precocious Puberty
• Puberty, Precocious

Intervention

Drug:
• Leuprolide

Locations

Country	Name	City	State
United States	Nemours Children's Hospital	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Nemours Children's Clinic	Tolmar Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Efficacy Endpoint	The percentage of subjects with serum LH concentrations <4 mIU/ml 30 minutes following an abbreviated GnRHa stimulation test at the month 6 visit	6 months	Yes