Safety and Efficacy of TAK-385 for Patients With Localized Prostate Cancer

The drug being tested in this study is called TAK-385. Men with prostate cancer benefit from
receiving androgen deprivation therapy (ADT) to minimize testosterone levels before, during
and after EBRT. This combination increases the potential success of treating their disease.
This study will see if TAK-385 [an oral gonadotropin-releasing hormone (GnRH) antagonist]
brings testosterone levels down sufficiently, with the convenience and comfort of taking a
pill. It will look at the time it takes to restore testosterone levels after radiation
therapy as well. One hundred participants will be assigned by chance (like flipping a coin)
to a treatment group: 60 to TAK-385, and 40 to degarelix.

Those assigned to TAK-385 will take a daily pill. Those assigned to degarelix will receive
an injection under the skin once every four weeks at the clinic. They will start radiation
therapy when testosterone is low enough, after at least 12 weeks of treatment. This trial
will be conducted at clinics in the United States (US) and United Kingdom (UK). Participants
will visit the clinic up to 14 times over 37 weeks for physical exams and blood tests, and
might receive one follow-up telephone call.

Inclusion Criteria:

1. Is male, 18 years of age or older.

2. Has histologically confirmed diagnosis of localized prostate adenocarcinoma of
intermediate risk for which 6-month neoadjuvant and adjuvant androgen deprivation
therapy (ADT) to external beam radiation therapy (EBRT) is indicated. Intermediate
risk per National Comprehensive Cancer Network (NCCN) guidelines includes one of the
following:

1. T2b-T2c disease, or

2. Gleason score 7, or

3. Prostate-specific antigen (PSA) 10-20 ng/mL.

3. Is scheduled for EBRT to begin ≥ 12 weeks after the Baseline visit.

4. Has serum testosterone at screening > 150 ng/dL (5.2 nmol/L).

5. Has screening serum PSA concentration > 2 ng/mL.

6. Has body mass index (BMI) ≥ 18.0 at screening or baseline.

7. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at
screening or baseline.

8. Is a male participant, even if surgically sterilized (i.e., status postvasectomy),
who: Agrees to practice effective barrier contraception during the entire study
treatment period and through 4 months after the last dose of study drug, or, Agrees
to practice true abstinence, when this is in line with the preferred and usual
lifestyle of the participant. (Periodic abstinence [e.g., calendar, ovulation,
symptothermal, postovulation methods for the female partner] and withdrawal are not
acceptable methods of contraception.).

9. Has given voluntary written consent before performance of any study-related procedure
not part of standard medical care, with the understanding that consent may be
withdrawn by the participant at any time without prejudice to future medical care.

10. Has suitable venous access for the study-required blood sampling, including
pharmacokinetic (PK) and pharmacodynamic sampling.

Exclusion Criteria:

1. Has metastatic disease (based on investigator evaluation and assuming no likely
metastatic pelvic lymph nodes > 1.0 cm in long axis diameter).

2. Had prior or current use of a gonadotropin-releasing hormone (GnRH) analog or
androgen receptor antagonist as first-line hormone therapy, unless total use was less
than 6 months and not more recently than 1 year before the planned baseline visit.

3. Had diagnosis of or treatment for another malignancy within 2 years before the first
dose of study drug, or previous diagnosis of another malignancy with evidence of
residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of
any type are not excluded if they have undergone complete resection.

4. Has abnormal screening and/or baseline laboratory values that suggest a clinically
significant underlying disease, or the following laboratory values:

1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.5 ×
institutional upper limit of the normal range (ULN);

2. Serum creatinine > 2.0 mg/dL;

3. Total bilirubin > 2.0 × institutional ULN (unless documented Gilbert's disease);

4. Uncontrolled diabetes (Hemoglobin A1c [HbA1c] > 10%) or previously undiagnosed
diabetes mellitus with HbA1c > 8%.

5. Has history of myocardial infarction, unstable symptomatic ischemic heart disease,
any ongoing cardiac arrhythmias of Grade > 2 (chronic stable atrial fibrillation on
stable anticoagulant therapy is allowed), thromboembolic events (e.g., deep vein
thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other
significant cardiac condition (e.g., pericardial effusion, restrictive
cardiomyopathy) within 6 months before receiving the first dose of study drug.

6. Has electrocardiogram (ECG) abnormalities of:

1. Q-wave infarction, unless identified 6 or more months before screening;

2. Heart rate-corrected QT interval (msec) (QTcF interval) > 480 msec. If QTcF is
prolonged in a participant with a pacemaker, the participant may be enrolled in
the study upon discussion with the project clinician;

3. If the QTcF interval is 450-480 msec, inclusive, in a participant with current
use of medications with known effects on QT interval, the participant may be
enrolled in the study following discussion with the project clinician.

7. Has congenital long QT syndrome.

8. Is currently using Class IA (e.g., quinidine, procainamide) or Class III (e.g.,
amiodarone, sotalol) antiarrhythmic medications.

9. Has uncontrolled hypertension despite appropriate medical therapy (sitting blood
pressure [BP] of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate
measurements no more than 60 minutes apart during the Screening visit). Participants
with systolic BP measurements > 160 mmHg may be rescreened. Participants with
systolic BP measurements 141-160 mmHg, although eligible, should be referred for
further management of hypertension if indicated.

10. Has known, previously diagnosed human immunodeficiency virus (HIV) infection, active
chronic hepatitis B or C, life-threatening illness unrelated to prostate cancer, or
any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with participation in this study. Specific screening for
chronic viral illness is at the discretion of the site and/or local institutional
review board (IRB).

11. Has received treatment with any investigational products within 3 months before the
first dose of study drug.

12. Is a primary family member (spouse, parent, child, or sibling) of anyone involved in
the conduct of the study or is a study site employee.

13. Has known gastrointestinal (GI) disease, condition or procedure that could interfere
with the oral absorption or tolerance of TAK-385, including difficulty swallowing
tablets.

14. Is using any medication or food products listed in the excluded medications and
dietary products table within 2 weeks before the first dose of study drug. This list
includes moderate and strong inhibitors or inducers of cytochrome P450 (CYP3A4/5) and
P-glycoprotein (P-gp). Participants must have no history of amiodarone use in the 6
months before the first dose of TAK-385.

15. Has admission or evidence of alcohol or drug abuse or use of illicit drugs.