Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Androgens

Hormones

Follicle Stimulating Hormone

Leuprolide

Testosterone

Antineoplastic Agents, Hormonal

Leuprolide acetate 22.5 mg depot administered twice, 3 months apart

Administered by im injection, twice during the study, three months apart

Leuprolide acetate 22.5 mg depot, GP-Pharm SA

Some patients with prostate cancer benefit from androgen deprivation therapy which reduces levels of testosterone. Leuprolide is a synthetic Luteinizing hormone releasing hormone (LHRH) analogue which upon administration can decrease testosterone levels to ≤0.5 ng/mL. Leuprolide Acetate 22.5 mg Depot is a microencapsulated formulation of leuprolide which is released slowly over time and effectively reduces testosterone levels in many patients to ≤0.5 ng/mL for up to three months. In this study Leuprolide acetate 22.5 mg Depot will be administered by intramuscular injection twice over a period of 6 months. The proportion of patients with testosterone ≤0.5 ng/mL evaluated over a period of 168 days.

This in an open-label, multicenter, multiple-dose investigation of 2 doses of leuprolide acetate 22.5 mg administered with a 3-month interval to patients with histologically proven carcinoma of prostate who might benefit from medical androgen deprivation therapy. A total of up to 160 male patients will receive their first single intramuscular injection of leuprolide acetate 22.5 mg on Day 0 (after baseline assessment) and then after 3 months (Day 84). The study duration will be 6 months. Thirty(30) patients will be screened per protocol and enrolled at selected centers to form the PK cohort. The PK/PD analysis will be performed using plasma specimens from the first 20 of 30 patients enrolled in the study (and included in the PK/PD cohort). Patients not belonging to the PK cohort will be screened and enrolled per protocol and will follow the same study schedule as those enrolled in the PK portion of the study, except they will provide only sparse PK sampling.

Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in Treatment of Prostate Cancer

Efficacy and Safety of a New Leuprolide Acetate 22.5 mg Depot Formulation in the Treatment of Prostate Cancer

The primary endpoint was testosterone ≤ 0.5 ng/mL assessed on Days 28, 84, and 168. Thereby, maintenance of castration was to be demonstrated through Day 168 with no missing data at these key time points, unless the missing data were due to an event unrelated to the study drug (ITT patients).

For purposes of calculating summary statistics, any concentration values Below Limit of Quantification (BLQ) were to be assigned ½ the Low Limit of Quantification (LLOQ) (LLOQ=2.00). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was calculated for that time point.

For purposes of calculating summary statistics, any concentration values Below Limit of Quantification (BLQ) were to be assigned ½ the Low Limit of Quantification (LLOQ) (LLOQ=3.66). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was to be calculated for that time point.

For purposes of calculating summary statistics, any concentration values Below Limit Quantification (BLQ) were to be assigned ½ the Low Limit Quantification (LLOQ) (LLOQ=0.36). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was calculated for that time point.

Leuprolide Pharmacokinetic Parameters (PK Population).

The WHO/ECOG, bone pain, urinary pain and urinary symptoms data reported are the most frequent percentage at the assessment time.

* The WHO/ECOG performance status was summarized using the 0 to 4 WHO/ECOG performance status scale. (0= fully active, able to carry on all pre-disease performances without restriction).
* Bone pain, urinary pain and urinary symptoms were determined using a 10-point scale (1= no pain/symptoms, 10= worst pain/symptom imaginable).

GP-Pharm

Leuprolide acetate 22.5 mg depot administered twice, 3 months apart

Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im injection, twice during the study, three months apart

Leuprolide Acetate 22.5 mg Depot

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Neal Shore MD

Leuprolide acetate 22.5 mg depot administered twice, 3 months apart.

Leuprolide acetate 22.5 mg depot, GP-Pharm SA: Administered by im (intramuscular) injection, twice during the study, three months apart.

Percentage of Participants Achieving Chemical Castration (Defined as Testosterone Levels ≤ 0.5 ng/mL) at Days 28, 84, and 168.

Baseline

Day 28

Day 168

Determination of Serum Luteinizing Hormone (LH)

Follicle-stimulating Hormone (FSH)

Prostate-specific Antigen (PSA) Concentrations

Day 0/Dose 1 Cmax

Day 84/Dose 2 Cmax

Determination of Leuprolide Cmax

Baseline WHO/ECOG Score 0 (n=161)

Day 168 WHO/ECOG Scores 0 (n=152)

Baseline Bone Pain score 1 (n=161)

Day 168 Bone Pain score 1 (n=152)

Baseline Urinary Pain score 1 (n=161)

Day 168 Urinary Pain Score 1 (n=152)

Baseline Urinary Symptoms score 1 (n=161)

Day 168 Urinary Symptoms score 1 (n=152)

Safety endpoints adverse events (AEs), local tolerability, vital signs, performance status, bone pain, urinary pain, and urinary symptoms, occurrence of hot flushes and clinical laboratory and electrocardiogram (ECG) results.

Spots Global Cancer Trial Database for androgen deprivation therapy.