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

AbbVie (prior sponsor, Abbott)72 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Precocious Leuprolide Acetate Luteinizing Hormone (LH)

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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.

Locations (20)

Site Reference ID/Investigator# 13521

Birmingham, Alabama, United States

Site Reference ID/Investigator# 14922

Long Beach, California, United States

Site Reference ID/Investigator# 26043

Los Angeles, California, United States

Site Reference ID/Investigator# 20802

San Diego, California, United States

Site Reference ID/Investigator# 22425

Greenwood Village, Colorado, United States

Site Reference ID/Investigator# 18181

Jacksonville, Florida, United States

Site Reference ID/Investigator# 26364

Pensacola, Florida, United States

Site Reference ID/Investigator# 26983

Indianapolis, Indiana, United States

Site Reference ID/Investigator# 20821

Shreveport, Louisiana, United States

Site Reference ID/Investigator# 23643

Minneapolis, Minnesota, United States

...and 10 more locations

Outcomes

Primary Outcomes

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.

Time frame: Day 1, Months 6, 12, 24, and 36

Secondary Outcomes

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.

Time frame: Day 1, Months 3, 6, 9, 12, and 24

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.

Time frame: Months 6, 9, 12, 24, 30, and 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.

Time frame: Day 1, Months 3, 6, 9, 12, 24, 30, and 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.

Time frame: Baseline of the lead-in study L-CP07-167, Day 1, Months 6, 12, 24, and 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.

Time frame: Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 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.

Time frame: Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 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.

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

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).

Time frame: Baseline (of the lead-in study L-CP07-167), and Day 1, Months 12, 24, and 36