A Study of Leuprolide to Treat Prostate Cancer

Official Title: “A Phase 3, Multi-Center, Open-Label, Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of Two 6-Month Leuprolide Formulations, in Subjects With Prostatic Adenocarcinoma”

To assess the efficacy and safety of 2 new formulations of leuprolide acetate 45 mg 6-month depot, Formulation A or Formulation B, for the treatment of patients with prostate cancer. A formulation will be deemed successful if the percentage of subjects with suppression of testosterone to <= 50 ng/dL from Week 4 to Week 48 is not less than 87%, (the lower bound of the 2-sided 90% confidence interval), a protocol-specified criterion.

A total of 300 male subjects were planned to be enrolled. Subjects were to receive a total of 2 intramuscular (IM) injections of the same formulation, either Formulation A or Formulation B, administered 24 weeks apart. The first 150 subjects were to receive Formulation A for both injections and the next 150 subjects were to receive Formulation B for both injections. The sponsor was to conduct an ongoing review of the primary endpoint data (suppression of testosterone <= 50 ng/dL) and planned to stop enrollment of Formulation A or Formulation B, or not to administer the second injection of Formulation A or Formulation B, if 15 or more subjects did not achieve testosterone suppression by Week 4 or failed to maintain testosterone suppression during the treatment period.

All analyses and summaries were to be conducted separately for subjects who received Formulation A or Formulation B.

This study was to be conducted at approximately 60-80 investigative sites. Subjects participated in the trial for approximately 14 months.

This trial was to include a Screening Period (up to 4 weeks), a 12-month Treatment Period (two 6-month treatment cycles), and a Follow-Up Period (30 days).

Intervention(s) in this Clinical Trial

• Drug: Leuprolide acetate - Formulation A
  • Leuprolide acetate was administered as 2 intramuscular (IM) injections of Formulation A, 45 mg 6 month depot, 24 weeks apart.
• Drug: Leuprolide acetate - Formulation B
  • Leuprolide acetate was administered as 2 intramuscular (IM) injections of Formulation B, 45 mg 6 month depot, 24 weeks apart.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Leuprolide acetate - Formulation A
  • Leuprolide acetate 45 mg, 6-month depot
• Experimental: Leuprolide acetate - Formulation B
  • Leuprolide acetate, 45 mg, 6-month depot

Primary Measures

• Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: Intent-to-treat (ITT) Population for the Primary Endpoint.
  • Time Frame: Week 4 to Week 48
    Safety Issue?: No
• Adjusted Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: ITT Population for the Primary Endpoint Adjusted
  • Time Frame: Week 4 to Week 48
    Safety Issue?: No
• Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation B: ITT Population for the Primary Endpoint Preplanned
  • Time Frame: Week 4 to Week 48
    Safety Issue?: No

Secondary Measures

• Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population
  • Time Frame: Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
    Safety Issue?: No
• Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population
  • Time Frame: Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
    Safety Issue?: No
• Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population
  • Time Frame: Week 24 before the second injection until 2 weeks after Week 24 (2 hours [h], 4 h, 8 h, 1 day [d], 2 d, 3-10 d, and 11-17 d postdose)
    Safety Issue?: No
• Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population
  • Time Frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
    Safety Issue?: No
• Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population
  • Time Frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
    Safety Issue?: No
• Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population
  • Time Frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
    Safety Issue?: No
• Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population
  • Time Frame: Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
    Safety Issue?: No
• Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population
  • Time Frame: Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
    Safety Issue?: No

Inclusion Criteria:

• Voluntarily sign an IRB-approved informed consent form and any required privacy statement/authorization form.
• Pre-trial serum testosterone level >150 ng/dL.
• Histologically-confirmed prostatic adenocarcinoma in Jewett Clinical Stage A2, B, C or D and TNM* classification cT1b-4, N: any, M: any.
• *Tumor/Nodes/Metastases
• Subjects with a rising PSA following radical prostatectomy defined as an increase of 0.2 ng/mL from the previous test on two consecutive testings or rising PSA following prostate irradiation using Phoenix Definition of a rise of greater than or equal to 2.0 ng/mL above the nadir.
• Prostate cancer and general clinical status is sufficient to warrant at least 48 weeks of continuous androgen deprivation treatment, without concomitant antiandrogen treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance status grades 0,1,or 2 at the time of pre-trial screening.
• Life expectancy of at least 18 months.
• Subjects with serum creatinine ≤1.9 mg/dL, bilirubin ≤2.0 mg/dL (unless Gilbert's syndrome with normal AST, ALT); AST and ALT ≤2.5 times the upper limit of normal.

Exclusion Criteria:

• Requires additional treatment including radical prostatectomy, radiotherapy or cryotherapy of local disease.
• Historical, clinical, or radiographic evidence of central nervous system metastases, including spinal cord metastasis.
• Clinical evidence of urinary tract obstruction.
• History of bilateral orchiectomy, adrenalectomy, or hypophysectomy.
• History of clinical hypogonadism.
• Current malignancy or history of malignancy except for prostate cancer or basal or squamous cell carcinoma of the skin.
• Clinical or laboratory evidence of any severe underlying disease state (excluding prostate cancer) that would place subjects in additional jeopardy by participating in this trial.
• Hypersensitivity to leuprolide, polylactic acid, or any excipient of the drug.
• Incomplete recovery from the effects of any major surgery.
• History of receiving of the following prostate cancer therapies within 8 weeks prior to the Screening Visit: chemotherapy, immunotherapy, antiandrogen, radiation therapy, cryotherapy, strontium, or biological response modifiers.
• History of prostatic surgery within 4 weeks prior to the Screening Visit.
• Received hormonal therapy, including GnRH analogs (less than or equal to 6 month depot administration), estrogen, Megace and phytotherapy, within 32 weeks prior to the Screening Visit and during the trial.
• Alternative medical therapies which have an estrogenic, androgenic, or antiandrogenic effect (including phyto-estrogens and phyto-androgens) within 12 weeks prior to the Screening Visit and during the trial.
• Requires the chronic use of systemic corticosteroids and anticonvulsants that may affect bone loss such as carbamazepine, phenobarbital, phenytoin, valproic acid or primidone.
• May require antiandrogen, immuno-, or surgical therapy for prostate cancer during the trial.
• History of alcoholism or consumes >14 alcoholic beverages per week or illicit drug abuse within 12 months prior to screening.
• Received therapy with a GnRH analog (1 year implant) within 60 weeks prior to the Screening Visit.
• Received therapy with finasteride or ketoconazole within 1 week prior to the Screening Visit; dutasteride within 25 weeks prior to the Screening Visit.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Abbott Industry

Overall Clinical Trial Officials and Contacts

Kristof Chwalisz, MD, PhD Study Director Abbott  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00626431

Study ID Number: L-PC07-169

ClinicalTrials.gov Identifier: NCT00626431

Health Authority: United States: Food and Drug Administration