Clinical Studies

 

1-MONTH ADMINISTRATION

In a single, 18-year study, 1-month LUPRON DEPOT-PED demonstrated sustained, reversible suppression with follow-up data through adulthood1-3

Study Design for LUPRON DEPOT-PED 1-Month Administration

The 1-month LUPRON DEPOT-PED study was a prospective, multicenter, longitudinal study from 1991 to 2009 divided into 2 key phases: The open-label treatment period and the long-term, post-treatment follow-up period.2

Primary endpoint:2,3

Suppression of clinical sexual characteristics

Secondary endpoints:4

Gonadotropin concentrations; Sex hormone concentrations; Predicted mature height based on bone age; Ratio of bone age to chronological age; Growth rate

 

Results for LUPRON DEPOT-PED 1-Month Administration

Suppression of clinical sexual characteristics, based on Tanner staging.

    During 5 Years of Treatment

  • 66.7% to 90.6% of females had suppression of breast development1
  • 60% to 100% of males had suppression of genitalia development1

    At 6 Months Post-treatment

  • In females (n=35), increase in breast development was 66.7%3
  • 4 of 5 males showed Tanner genital stage advancement by Month 63

 

Secondary Endpoint Results for LUPRON DEPOT-PED 1-Month Administration

1-month LUPRON DEPOT-PED provided sustained suppression of mean peak LH, with hormone levels usually restored within 6 months of stopping treatment1

Mean Peak LHa Was Suppressed Throughout Treatment and Recovered After Therapy

 

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of patients achieved suppression by Week 4 of treatment with LUPRON DEPOT-PED1

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were suppressed to prepubertal levels during the first 5 years of treatment1

 

Long-term study showed that growth and bone maturation normalized in patients treated with 1-month LUPRON DEPOT-PED2

Mean growth rate was 10.6 cm/year at baseline2

 

Through year 5, growth rate ranged from 3.4 to 5.6 cm/year1

 

Bone maturation was delayed with therapy. Mean ratio of bone age to chronological age decreased from 1.5 at baseline to 1.1 by end of treatment1

 

Those patients observed
until they reached adult height had a mean increase in final adult height over predicted adult height, with a mean height standard deviation score of –0.21

Girls resumed reproductive development following treatment with 1-month LUPRON DEPOT-PED1

Mean time to menses was ~1.5 years1            |            Mean age was 12.9 years1


Safety Considerations1

During the early phase of therapy, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug. An increase in clinical signs and symptoms of puberty may be observed.

Psychiatric events have been reported in patients taking GnRH agonists, including LUPRON DEPOT‑PED. Events include emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms during treatment.

 

3-Month Administration

Sustained suppression with 3-month administration of LUPRON DEPOT-PED1

Study Design for LUPRON DEPOT-PED 3-Month Administration

Randomized, open-label clinical trial to assess the safety and efficacy of LUPRON DEPOT-PED 11.25 and 30 mg for 3-month administration in 84 subjects (n=76 females, n=8 males) with CPP between 1 and 11 years of age1

  • Efficacy was measured as the suppression of peak stimulated LH to < 4.0 mIU/mL, assessed at Months 2, 3, and 61
  • Both treatment groups had equal numbers of naïve and previously treated patients1

3-month 30-mg dosing suppressed LH concentrations at Months 2, 3, and 61

 

Stimulated and basal gonadotropins were reduced to prepubertal levels in 95.2% of patients with CPP.1

 

Suppression of Peak Stimulated LH< 4 mIU/mLa From Month 2 Through Month 6
With LUPRON DEPOT-PED 30 mg Every 3 Months1

Percent with suppression

Naïve (n=21)

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95% CI (%)c:

69.6, 98.8

Previous Treatmentb (n=21)

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95% CI (%)c:

83.9, 100

Total (n=42)

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95% CI (%)c:

83.8, 99.4

aPrimary endpoint.
bPreviously treated with GnRHa for at least the 6 months prior to enrollment in the study.
c2-sided 95% CI.

 

All LUPRON DEPOT-PED 1-month doses were represented in the previously treated patient population.6

 

Disposition of Previously Treated Patients in the 3-Month 30-mg Dosing Study Group (n=21)6,a

Prestudy Dose 30 mg Every
3 Months, No.
7.5 mg for 1 month 8
11.25 mg for 1 month 6
15 mg for 1 month 3
11.25 mg for 3 monthsb 4
Treatment Failures 0

aPreviously treated with GnRHa for at least the 6 months prior to study enrollment. Dosing was randomized for both prestudy and study treatments.

bThis formulation was not approved to treat central precocious puberty at the time of the study.

 

100% (n=42) of patients had sex steroid suppression to prepubertal levels* at all visits with LUPRON DEPOT-PED 30 mg for 3-month administration1

*Estradiol < 20 pg/mL or testosterone < 30 ng/dL.

 

 

Adverse Reactions

  • The most common adverse reactions with GnRH agonists, including LUPRON DEPOT-PED 7.5 mg, 11.25 mg, or 15 mg for 1-month administration and LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration, are injection site reactions/pain including abscess, general pain, headache, emotional lability and hot flushes/sweating.1

 

Percentage of patients with treatment-emergent adverse reactions occurring in ≥2% of pediatric patients receiving LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month duration:

Adverse Reaction No. (%) of patients
receiving 11.25 mg
(n=42)		 No. (%) of patients
receiving 30 mg
(n=42)
Injection site pain 8 (19) 9 (21)
Weight increased 3 (7) 3 (7)
Headache 1 (2) 3 (7)
Mood altered 2 (5) 2 (5)
Injection site swelling 1(2) 1 (2)


 

Open Label Extension Study

Open-Label Extension Study Provides Long-Term Data With 3-Month Dosing5

Study Design for LUPRON DEPOT-PED Extension Study

Phase 3, open-label, multicenter extension study

Objective: Assess the long-term safety of continued treatment with 11.25- and 30-mg 3-month LUPRON DEPOT-PED over 36 months of treatment in children with CPP.

  • Objective included the maintenance of LH suppression and the effects on pubertal symptoms, sex steroid levels, and bone age

Study population:

  • Included 65 female and 7 male subjects with CPP
    • Ranged from 2–11 years of age at the beginning of the pivotal 6-month study
  • Subjects had received 6 months of LUPRON DEPOT-PED at doses of 11.25 mg (n=34) or 30 mg (n=38) IM every 3 months during the pivotal study
    • Patients continued the same treatment in this 36-month extension study
  • All subjects had successfully completed the pivotal 6-month lead-in study with maintained LH suppression

Results for LUPRON DEPOT-PED 3-Month 30-mg Administration

Patients Completing and Discontinuing5

  • 24 subjects completed the 36-month treatment period
  • 48 subjects discontinued the study
    • -The most common resason for discontinuation of treatment was that the individual was considered ready for progress through physiologic puberty

 

Safety Considerations

  • LUPRON DEPOT-PED is contraindicated in patients who are hypersensitive to gonadotropin-releasing hormone (GnRH), GnRH agonists, or any of the product excipients or in females who are or may become pregnant during treatment, as LUPRON DEPOT-PED may cause fetal harm.
  • Increased clinical signs and symptoms of puberty, including vaginal bleeding, may occur during the first weeks of drug therapy or after subsequent doses.
  • Psychiatric events have been reported in patients taking GnRH agonists, including LUPRON DEPOT-PED. Postmarketing reports include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms during treatment.
  • Convulsions have been observed postmarketing in patients taking GnRH agonists, including LUPRON DEPOT-PED, with or without a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications that have been associated with convulsions, such as bupropion and selective serotonin reuptake inhibitors (SSRIs). Convulsions have also been reported in patients in the absence of any of the conditions mentioned above.
  • Pseudotumor cerebri (idiopathic intracranial hypertension) have been reported in pediatric patients receiving GnRH agonists, including LUPRON DEPOT-PED. Monitor patients for signs and symptoms of pseudotumor cerebri, including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.
  • Diagnostic tests of pituitary gonadotropic and gonadal functions may be affected when conducted during treatment and up to 6 months after discontinuation.