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
  Purpose

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).


Condition Intervention Phase
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
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).



Enrollment: 72
Study Start Date: December 2008
Study Completion Date: January 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Leuprolide Acetate 3 Month Depot
Other Names:
  • ABT-818
  • Lupron
  • Leuprorelin acetate
Experimental: Leuprolide Acetate 3M Depot 30 mg
Twelve intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 months apart.
Drug: Leuprolide Acetate 3 Month Depot
Other Names:
  • ABT-818
  • Lupron
  • Leuprorelin acetate

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00667446

Locations
United States, Alabama
Site Reference ID/Investigator# 13521
Birmingham, Alabama, United States, 35233
United States, California
Site Reference ID/Investigator# 14922
Long Beach, California, United States, 90806
Site Reference ID/Investigator# 26043
Los Angeles, California, United States, 90027
Site Reference ID/Investigator# 20802
San Diego, California, United States, 92123
United States, Colorado
Site Reference ID/Investigator# 22425
Greenwood Village, Colorado, United States, 80111
United States, Florida
Site Reference ID/Investigator# 18181
Jacksonville, Florida, United States, 32207
Site Reference ID/Investigator# 26364
Pensacola, Florida, United States, 32504
United States, Indiana
Site Reference ID/Investigator# 26983
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Site Reference ID/Investigator# 20821
Shreveport, Louisiana, United States, 71130-3932
United States, Minnesota
Site Reference ID/Investigator# 23643
Minneapolis, Minnesota, United States, 55455
Site Reference ID/Investigator# 23502
St. Paul, Minnesota, United States, 55102
United States, Missouri
Site Reference ID/Investigator# 14121
Kansas City, Missouri, United States, 64108
United States, Oklahoma
Site Reference ID/Investigator# 23802
Oklahoma City, Oklahoma, United States, 73104
Site Reference ID/Investigator# 13324
Tulsa, Oklahoma, United States, 74135
United States, Pennsylvania
Site Reference ID/Investigator# 16506
Hershey, Pennsylvania, United States, 17033
United States, Washington
Site Reference ID/Investigator# 14024
Seattle, Washington, United States, 98104
Puerto Rico
Site Reference ID/Investigator# 23182
Bayamon, Puerto Rico, 00960
Site Reference ID/Investigator# 21721
Ponce, Puerto Rico, 00717-2116
Site Reference ID/Investigator# 25908
Rio Piedras, Puerto Rico, 00935
Site Reference ID/Investigator# 23082
San Juan, Puerto Rico, 00936-8344
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Peter Bacher, MD AbbVie
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00667446     History of Changes
Other Study ID Numbers: L-CP07-177
Study First Received: April 24, 2008
Results First Received: October 16, 2013
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
Central Precocious Puberty
GnRH analog
Luteinizing hormone (LH)
Gonadotrophin-releasing hormone agonist(GnRHa)
Suppression of LH
Gonadotrophin-releasing hormone (GnRH)
CPP
Leuprolide acetate
Depot formulation
Lupron
Tanner staging
Pediatrics

Additional relevant MeSH terms:
Puberty, Precocious
Gonadal Disorders
Endocrine System Diseases
Leuprolide
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014