A Phase 1/2, Open-Label Study in Men with Prostate Cancer to Assess the Safety, Pharmacokinetics, and Testosterone-Lowering Efficacy of TAK-448, Administered as a 1 Month Depot, Including a Randomized Portion With a Group Administered Leuprorelin

INTERVENTION: Product Name: TAK‐448‐SR (1M) Pharmaceutical Form: Powder and solvent for suspension for injection Current Sponsor code: TAK‐448 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 15‐ Pharmaceutical form of the placebo: Solvent for parenteral use Route of administration of the placebo: Subcutaneous use Pharmaceutical Form: Powder and solvent for suspension for injection INN or Proposed INN: LEUPRORELIN CAS Number: 53714560 CONDITION: Prostate cancer ; MedDRA version: 12.1 Level: LLT Classification code 10007113 Term: Cancer of prostate PRIMARY OUTCOME: Main Objective: Protocol phase 1:; ‐ To assess the safety and pharmacokinetics of TAK 448 in patients receiving a single dose of a 1 month depot formulation of TAK‐448; ; Protocol phase 2:; ‐ To assess the safety in patients receiving repeated doses of a 1‐month depot formulation of TAK‐448; ‐ To assess the effect of repeated doses of a 1 month depot formulation of TAK 448 on serum testosterone concentrations; ‐ To assess the pharmacokinetics of TAK 448 in patients receiving multiple doses of a 1 month depot formulation of TAK‐448 Primary end point(s): Phase 1 of the protocol:; ; ‐ Safety (vital signs, 12‐lead ECG, clinical laboratory tests, injection site‐related skin reactions, adverse events); ‐ Pharmacokinetics of TAK‐448 (Cmax on Day 1, AUC(0‐24h), AUC(0‐29 days), AUC(0‐last), time of last quantifiable concentration); ; Phase 2 of the protocol:; ; ‐ Safety (vital signs, 12‐lead ECG, clinical laboratory tests, injection site‐related skin reactions, adverse events); ‐ Pharmacodynamics (serum testosterone level and proportion of patients below castrate‐level serum testosterone on Day 1 of each month of therapy); ‐ Pharmacokinetics of TAK‐448 (AUC(0‐end of month 1), trough concentration on Day 1 of each month of therapy) Secondary Objective: Protocol phase 1:; ‐ In patients not on concomitant GnRH agonist therapy: to assess the effect of a 1 month depot formulation of TAK‐448 on serum testosterone and luteinizing hormone (LH); ; Protocol phase 2:; ‐ To assess the effect of a 1‐month depot formulation of TAK 448 on serum PSA concentration INCLUSION CRITERIA: The following criteria must be met by each patient to be eligible for the phase 1 or phase 2 portion of the study, unless otherwise specified: 1. Male 40 to 72 years of age, inclusive. 2. Histologically‐confirmed adenocarcinoma of the prostate, having completed primary local treatment at least 6 months prior to screening. 3. Screening serum PSA concentration > 2 ng/mL. 4. For the phase 1 portion of the study only: Either a) Concurrent GnRH therapy with generally indolent or stable disease with PSA DT >6 months and absolute PSA <30 ng/mL and if metastatic disease, asymptomatic with only bone scan positive evidence of metastases. Patients with recurrent local disease will be asymptomatic without bladder, bowel, or obstructive symptoms. OR b) If not receiving GnRH therapy, a potential candidate for GnRH at some time in the future, i.e. in a period of ‘watchful waiting’ with generally indolent or stable disease with PSA DT >6 mon