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

Primary Purpose

Precocious, Leuprolide Acetate, Luteinizing Hormone (LH)

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Leuprolide Acetate 3 Month Depot
Sponsored by
AbbVie (prior sponsor, Abbott)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Precocious focused on measuring GnRH analog, Luteinizing hormone (LH), Gonadotrophin-releasing hormone agonist(GnRHa), Suppression of LH, Gonadotrophin-releasing hormone (GnRH), CPP, Leuprolide acetate, Central Precocious Puberty, Depot formulation, Lupron, Tanner staging, Pediatrics

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Site Reference ID/Investigator# 13521
  • Site Reference ID/Investigator# 14922
  • Site Reference ID/Investigator# 26043
  • Site Reference ID/Investigator# 20802
  • Site Reference ID/Investigator# 22425
  • Site Reference ID/Investigator# 18181
  • Site Reference ID/Investigator# 26364
  • Site Reference ID/Investigator# 26983
  • Site Reference ID/Investigator# 20821
  • Site Reference ID/Investigator# 23643
  • Site Reference ID/Investigator# 23502
  • Site Reference ID/Investigator# 14121
  • Site Reference ID/Investigator# 23802
  • Site Reference ID/Investigator# 13324
  • Site Reference ID/Investigator# 16506
  • Site Reference ID/Investigator# 14024
  • Site Reference ID/Investigator# 23182
  • Site Reference ID/Investigator# 21721
  • Site Reference ID/Investigator# 25908
  • Site Reference ID/Investigator# 23082

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Leuprolide Acetate 3M Depot 11.25 mg

Leuprolide Acetate 3M Depot 30 mg

Arm Description

Twelve intramuscular injections of leuprolide acetate for depot suspension 11.25 mg administered 3 months (3M) apart.

Twelve intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 months apart.

Outcomes

Primary Outcome Measures

Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone
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)
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)
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
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
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)
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)
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
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
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).

Full Information

First Posted
April 24, 2008
Last Updated
January 8, 2014
Sponsor
AbbVie (prior sponsor, Abbott)
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1. Study Identification

Unique Protocol Identification Number
NCT00667446
Brief Title
Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
GnRH analog, Luteinizing hormone (LH), Gonadotrophin-releasing hormone agonist(GnRHa), Suppression of LH, Gonadotrophin-releasing hormone (GnRH), CPP, Leuprolide acetate, Central Precocious Puberty, Depot formulation, Lupron, Tanner staging, Pediatrics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Leuprolide Acetate 3M Depot 11.25 mg
Arm Type
Experimental
Arm Description
Twelve intramuscular injections of leuprolide acetate for depot suspension 11.25 mg administered 3 months (3M) apart.
Arm Title
Leuprolide Acetate 3M Depot 30 mg
Arm Type
Experimental
Arm Description
Twelve intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 months apart.
Intervention Type
Drug
Intervention Name(s)
Leuprolide Acetate 3 Month Depot
Other Intervention Name(s)
ABT-818, Lupron, Leuprorelin acetate
Primary Outcome Measure Information:
Title
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone
Description
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.
Time Frame
Day 1, Months 6, 12, 24, and 36
Secondary Outcome Measure Information:
Title
Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1)
Description
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.
Time Frame
Day 1, Months 3, 6, 9, 12, and 24
Title
Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2)
Description
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.
Time Frame
Months 6, 9, 12, 24, 30, and 36
Title
Percentage of Male Participants With Suppression of Basal Testosterone
Description
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.
Time Frame
Day 1, Months 3, 6, 9, 12, 24, 30, and 36
Title
Mean Peak-stimulated Luteinizing Hormone Concentration by Visit
Description
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.
Time Frame
Baseline of the lead-in study L-CP07-167, Day 1, Months 6, 12, 24, and 36
Title
Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development)
Description
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.
Time Frame
Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36
Title
Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development)
Description
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.
Time Frame
Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36
Title
Change From Baseline in Growth Rate
Description
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.
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
Title
Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age
Description
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).
Time Frame
Baseline (of the lead-in study L-CP07-167), and Day 1, Months 12, 24, and 36

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Bacher, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference ID/Investigator# 13521
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Site Reference ID/Investigator# 14922
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Site Reference ID/Investigator# 26043
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Site Reference ID/Investigator# 20802
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Site Reference ID/Investigator# 22425
City
Greenwood Village
State/Province
Colorado
ZIP/Postal Code
80111
Country
United States
Facility Name
Site Reference ID/Investigator# 18181
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Site Reference ID/Investigator# 26364
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
Site Reference ID/Investigator# 26983
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Site Reference ID/Investigator# 20821
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71130-3932
Country
United States
Facility Name
Site Reference ID/Investigator# 23643
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Site Reference ID/Investigator# 23502
City
St. Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Site Reference ID/Investigator# 14121
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Site Reference ID/Investigator# 23802
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Site Reference ID/Investigator# 13324
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74135
Country
United States
Facility Name
Site Reference ID/Investigator# 16506
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Site Reference ID/Investigator# 14024
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Site Reference ID/Investigator# 23182
City
Bayamon
ZIP/Postal Code
00960
Country
Puerto Rico
Facility Name
Site Reference ID/Investigator# 21721
City
Ponce
ZIP/Postal Code
00717-2116
Country
Puerto Rico
Facility Name
Site Reference ID/Investigator# 25908
City
Rio Piedras
ZIP/Postal Code
00935
Country
Puerto Rico
Facility Name
Site Reference ID/Investigator# 23082
City
San Juan
ZIP/Postal Code
00936-8344
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
24926950
Citation
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.
Results Reference
derived
Links:
URL
http://rxabbvie.com
Description
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Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty

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