Clinical Studies

LUPRON DEPOT-PED 1-Month Administration

Sustained, reversible suppression with 1-month CPP therapy, demonstrated through 18 years of clinical trial data1,2

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 endpoint2,3:

Suppression of clinical sexual characteristics

Secondary endpoints4:

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

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

Mean Incremental Growth Rates (With Standard Deviation)5

Reproductive Function Post-Treatment for LUPRON DEPOT-PED 1-Month Administration

Girls treated with LUPRON DEPOT-PED resumed normal pubertal development and began menstruation after treatment ended

The mean time to menses was approximately

1.5 years

after stopping treatment1

12 pregnancies were reported in 7 of 20 women1

Include multiple pregnancies in 4 women

(post-treatment survey; n=20)


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
  • 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.
  • Postmarketing reports of convulsions have been observed in patients on GnRH agonists, including LUPRON DEPOT‑PED. These included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absense of any of the conditions mentioned above.1
     

LUPRON DEPOT-PED 3-Month Administration

Sustained suppression that continued throughout treatment with 3-month
30 mg administration1

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

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

 

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.7

 

Disposition of Previously Treated Patients in the 3-Month 30-mg Dosing Study Group (n=21)a,7

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.
b
This 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.
  • 2 female patients did not achieve the primary efficacy endpoint in the treatment-naïve 30-mg arm of the study8
    • Patient 1: Month 2 (LH: 4.5 mIU/mL). LH peak values dropped to 2.5 mIU/mL at Month 3. Patient only received first injection during study
    • Patient 2: Month 2 (LH: 11 mIU/mL). No evidence that the peak LH dropped any time post Month 2. Patient only received first injection during study

 

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

 

Open Label Extension Study

Open-Label Extension Study Provides Long-Term Data With 3-Month Dosing6

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 Discontinuing

  • 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

 

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
  • New occurrence of the following symptoms were seen in the open-label extension10:
    • - Anger (n=1), vaginal discharge (n=1), and vaginal hemorrhage (n=1)

References: 1.  LUPRON DEPOT-PED [package insert]. North Chicago, IL: AbbVie Inc.  2. Lee PA, Neely EK, Fuqua J, et al. Efficacy of leuprolide acetate 1-month depot for central precocious puberty (CPP): growth outcomes during a prospective, longitudinal study. Int J Pediatr Endocrinol. 2011; 2011(1):7. doi:10.1186/1687-9856-2011-7. Epub 2011 Jul 12. 3. Neely EK, Lee PA, Bloch CA, et al. Leuprolide acetate 1-month depot for central precocious puberty: hormonal suppression and recovery. Int J Pediatr Endocrinol. 2010;2010:398639. doi:10.1155/2010/398639. Epub 2011 4. Data on file ABVRRTI62554, AbbVie, Inc. 5. Data on file ABVRRTI62559. AbbVie, Inc. 6. Lee PA, Klein K, Mauras N, Lev-Vaisler T, Bacher P. 36-month treatment experience of two doses of leuprolide acetate 3-month depot for children with central precocious puberty. J Clin Endocrinol Metab. 2014;99(9):3153-3159.  7. Data on file ABVRRTI62799. AbbVie, Inc. 8. Data on file ABVRRTI62801. AbbVie, Inc. 9. Data on file ABVRRTI63014. AbbVie, Inc. 10. Data on file ABVRRTI63015. AbbVie, Inc.