Efficacy, Safety, and Pharmacokinetics of Leuprolide Mesylate in Subjects With Central Precocious Puberty

Inclusion Criteria:

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

2. Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have notreceived prior GnRHa treatment for CPP.

3. Pubertal-type LH response at 60 minutes post GnRHa stimulation test before treatmentinitiation > 5 mIU/mL.

4. Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development infemales 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 ≥ 1year.

7. Bone age < 13 years for girls and < 14 years for boys.

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

9. Signed Assent by patients as per IRB/IEC requirements.

Exclusion Criteria:

1. Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretionof gonadotropins or gonadotropin-independent gonadal or adrenal sex steroidsecretion. This includes true CPP triggered by other conditions, such as congenitaladrenal hyperplasia.

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 requiringneurosurgery or cerebral irradiation. Patients with hamartomas or adenomas notrequiring surgery are eligible.

5. Any other condition, chronic illness or treatment that, in the opinion of theInvestigator, may interfere with growth or other study endpoints (e.g., chronicsteroid use [except mild topical steroids], renal failure, diabetes, moderate tosevere scoliosis, previously treated intracranial tumor).

6. Prior or current therapy with medroxyprogesterone acetate, growth hormone orinsulin-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 standard deviations (SD) below the meanheight 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 ofthe Investigator, may make it undesirable for the patients to participate in thestudy.

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 inprior clinical studies before the baseline visit (Day 0).

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

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