Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00667446
First received: April 24, 2008
Last updated: January 8, 2014
Last verified: January 2014

April 24, 2008
January 8, 2014
December 2008
October 2012   (final data collection date for primary outcome measure)
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone [ Time Frame: Day 1, Months 6, 12, 24, and 36 ] [ Designated as safety issue: No ]
Luteinizing Hormone (LH) suppression is defined as peak-stimulated LH < 4 mIU/mL. Peak-stimulated LH refers to the maximum LH concentration measured 30 and 60 minutes after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test. Participants who failed suppression at previous visit and prematurely discontinued were counted as having failed future visits also. Final visit is the participant's last visit closest to Month 36.
Suppression of luteinizing hormone concentrations (<4 mIU/mL). [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00667446 on ClinicalTrials.gov Archive Site
  • Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) [ Time Frame: Day 1, Months 3, 6, 9, 12, and 24 ] [ Designated as safety issue: No ]

    The percentage of female participants with suppression of basal estradiol to prepubertal levels, defined as estradiol < 20 pg/mL.

    The estradiol assay was changed in June of 2010, and the lower limit of quantitation (LLOQ) was increased from 1 pg/mL to 10 pg/mL. This outcome measure reports data for assays performed before this change occurred, with an LLOQ of 1 pg/mL. Final visit is the participant's last visit closest to Month 36.

  • Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) [ Time Frame: Months 6, 9, 12, 24, 30, and 36 ] [ Designated as safety issue: No ]

    The percentage of female participants with suppression of basal estradiol to prepubertal levels, defined as estradiol < 20 pg/mL.

    The estradiol assay was changed in June of 2010, and the lower limit of quantitation (LLOQ) was increased from 1 pg/mL to 10 pg/mL. This outcome measure reports data for assays performed after this change occurred, with an LLOQ of 10 pg/mL. Final visit is the participant's last visit closest to Month 36.

  • Percentage of Male Participants With Suppression of Basal Testosterone [ Time Frame: Day 1, Months 3, 6, 9, 12, 24, 30, and 36 ] [ Designated as safety issue: No ]
    The percentage of male participants with suppression of basal testosterone to prepubertal levels, defined as testosterone < 30 ng/dL. Final visit is the participant's last visit closest to Month 36.
  • Mean Peak-stimulated Luteinizing Hormone Concentration by Visit [ Time Frame: Baseline of the lead-in study L-CP07-167, Day 1, Months 6, 12, 24, and 36 ] [ Designated as safety issue: No ]
    Peak-stimulated luteinizing hormone refers to the maximum luteinizing hormone concentration measured 30 and 60 minutes after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test. Final visit is the participant's last visit closest to Month 36.
  • Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) [ Time Frame: Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36 ] [ Designated as safety issue: No ]
    The percentage of female participants with suppression of breast development. Breast development was rated from Stage 1 (early development) through Stage 5 (full development) according to a modified Tanner Staging pictogram. Suppression of breast development is defined as regression or no progression of breast development from Baseline (of the lead-in study L-CP07-167) according to pubertal staging. Girls entering the study with fully developed breasts (Stage 5) were excluded from this analysis. Final visit is the participant's last visit closest to Month 36.
  • Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) [ Time Frame: Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36 ] [ Designated as safety issue: No ]
    The percentage of male participants with suppression of testicular volume and genital staging. Testicular volume was calculated from the length, width and height of each testicle measured by ultrasound. External genital development (testes and penis) was rated from Stage 1 (early development) through Stage 5 (full development) according to a modified Tanner Staging pictogram. Suppression is defined as regression or no progression in both testicular volume and genital staging from Baseline (of the lead-in study L-CP07-167) according to pubertal staging. Boys entering the study with fully developed genitals (Stage 5) were excluded from this analysis. Final visit is the participant's last visit closest to Month 36.
  • Change From Baseline in Growth Rate [ Time Frame: Baseline (the 1 year prior to the start of treatment in the lead-in study), and Day 1, Months 6, 12, 18, 24, 30, and 36 ] [ Designated as safety issue: No ]
    Baseline growth rate was the growth rate in the one year prior to Day 1 of the lead-in study L-CP07-167. Growth rates were calculated as the ratio of the change in height to the change in chronological age with an approximate 6-month interval for Day 1, Months 6, 12, 18, 24, 30, 36 and the Final Treatment Visit.
  • Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age [ Time Frame: Baseline (of the lead-in study L-CP07-167), and Day 1, Months 12, 24, and 36 ] [ Designated as safety issue: No ]

    Bone age was determined by left hand/wrist bone age radiographs that were evaluated using the Fels Method by a central reader. The ratio of change from Baseline in bone age (BA)/change from Baseline in chronological age (CA) was calculated using the following formula:

    (BA at Post-baseline Treatment Visit - BA at Baseline) / (CA at Post-baseline Treatment Visit - CA at Baseline).

  • Suppression of sex steroids (estradiol <20 pg/mL in girls and testosterone <30 ng/dL in boys). [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: Yes ]
  • Peak stimulated luteinizing hormone concentrations. [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: Yes ]
  • Suppression of the physical signs of puberty. [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: Yes ]
  • Change from baseline (from the lead-in study) in growth rate within each of the subgroups of children not previously treated and and previously treated. [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: Yes ]
  • The ratio of change from baseline (form the lead-in study) in bone age/change from baseline in chronological age within each of the subgroups of children not previously treated and previously treated. [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty
A 36 Month, Multi-Center, Open-Label Extension Study to Evaluate the Safety of Leuprolide Acetate 11.25 mg and 30 mg Formulations in Children With Central Precocious Puberty

The purpose of this extension study is to determine if leuprolide acetate (11.25 mg and 30 mg) is safe in treating children with Central Precocious Puberty over a longer period of time (36 months).

This study includes a 36-month Study Drug Treatment Period (3-month treatment cycles), and a Safety Follow-up Period (12 weeks following the Month 36 visit). Participants will receive a total of twelve injections of the same treatment they received in the lead-in study, L-CP07-167 (NCT00635817) either leuprolide acetate 11.25 mg or 30 mg depot formulation. Each injection will be administered 3 months apart for up to 36 months of treatment. Study visits will occur on Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30 and 33 (1st through the 12th leuprolide acetate depot injections, respectively), Month 36, and 12 weeks later for the Safety Follow-up Visit.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Precocious
  • Leuprolide Acetate
  • Luteinizing Hormone (LH)
  • Gonadotrophin-releasing Hormone Agonist (GnRHa)
  • Tanner Staging
  • Depot Formulation
  • Suppression of LH
  • Central Precocious Puberty (CPP)
  • Gonadotrophin-releasing Hormone (GnRH)
  • Lupron
  • GnRH Analog
  • Pediatrics Central Precocious Puberty
Drug: Leuprolide Acetate 3 Month Depot
Other Names:
  • ABT-818
  • Lupron
  • Leuprorelin acetate
  • Experimental: Leuprolide Acetate 3M Depot 11.25 mg
    Twelve intramuscular injections of leuprolide acetate for depot suspension 11.25 mg administered 3 months (3M) apart.
    Intervention: Drug: Leuprolide Acetate 3 Month Depot
  • Experimental: Leuprolide Acetate 3M Depot 30 mg
    Twelve intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 months apart.
    Intervention: Drug: Leuprolide Acetate 3 Month Depot
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 Sep;99(9):3153-9. doi: 10.1210/jc.2013-4471. Epub 2014 Jun 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
72
January 2013
October 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subject completed the Treatment Period of the lead-in study, L-CP07-167 (NCT00635817), and has documented luteinizing hormone suppression as evidenced by peak-stimulated luteinizing hormone <4 mIU/mL at the Month 6 study visit of the lead-in study.
  • Demonstrated suppression of the physical signs of puberty at Month 6 of the lead-in study.
  • Subject is expected to receive at least 12 months of therapy to treat Central Precocious Puberty after study entry.
  • In general good health with no uncontrolled, clinically significant disease which would interfere with bone maturation or mask the objectives of this protocol as assessed by the investigator.

Exclusion Criteria:

  • Incomplete precocious puberty, peripheral precocious puberty or evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid and gonadal function (other than premature secretion of gonadotropins) not adequately controlled, unstable intracranial tumors except hamartoma.
  • Bone age ≥14 years for girls and ≥15 years for boys (based on the Month 6 lead in study, L-CP07-167, radiographic results).
  • Has an abnormal laboratory value suggesting a clinically significant underlying disease or condition.
  • Chronic illness requiring treatment that may interfere with growth, ie, chronic steroid use, renal failure, moderate to severe scoliosis.
  • Current therapy with medroxyprogesterone acetate.
  • Current therapy with growth hormone.
  • Current therapy with insulin-like growth factor-1 (IGF-1).
  • Current use of an estrogen preparation.
  • Any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk or that affects subject compliance.
  • Subject has a positive pregnancy test.
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00667446
L-CP07-177
No
AbbVie ( AbbVie (prior sponsor, Abbott) )
AbbVie (prior sponsor, Abbott)
Not Provided
Study Director: Peter Bacher, MD AbbVie
AbbVie
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP