Safety and Efficacy of TAK-385 for Patients With Localize... | NCT02135445

ID	Type	Description
U1111-1152-9537	Other Identifier	World Health Organization
2013-005002-53	EudraCT Number
14/LO/1052	Registry Identifier	NRES

Label	Type	Description	Intervention Names
TAK-385	Experimental	TAK-385 320 mg, tablets, orally, once, on Day 1, followed by TAK-385 120 mg, orally, once daily for 24 weeks. Each participant may have one upward dose adjustment of 40 mg for efficacy and/or one downward dose adjustment of 40 mg for safety during the study.	Drug: TAK-385
Degarelix	Active Comparator	Degarelix 240 mg, injection, subcutaneous, on Day 1, followed by degarelix 80 mg, injection, subcutaneous, once every four weeks, for 24 weeks.	Drug: Degarelix

Name	Type	Description	Arm Group Labels	Other Names
TAK-385	Drug	TAK-385 tablet	TAK-385
Degarelix

Measure	Description	Time Frame
Percentage of Participants With Effective Castration Rate Over 25 Weeks	Castration rate is defined as the observed percentage of participants who have testosterone concentrations less than (<) 50 nanogram per deciliter (ng/dL) (1.73 nanomole per liter [nmol/L]) at all scheduled visits.	Day 1 Week 5 up to Day 1 Week 25

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs		Baseline up to Week 29
Number of Participants With TEAEs Related to Physical Findings		Baseline up to Week 29

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Is male, 18 years of age or older.
Has histologically confirmed diagnosis of localized prostate adenocarcinoma of intermediate risk for which 6-month neoadjuvant and adjuvant androgen deprivation therapy (ADT) to 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 nanogram per milliliter (ng/mL).
Is scheduled for EBRT to begin greater than or equal to (>=) 12 weeks after the Baseline visit.
Has serum testosterone at screening greater then (>) 150 nanogram per deciliter (ng/dL) (5.2 nanomoles per liter [nmol/L]).
Has screening serum PSA concentration >2 ng/mL.
Has body mass index (BMI) >=18.0 at screening or baseline.
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening or baseline.
Is a male participant, even if surgically sterilized (that is, 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 [example, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.).
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.
Has suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) and pharmacodynamic sampling.

Exclusion Criteria:

Has metastatic disease (based on investigator evaluation and assuming no likely metastatic pelvic lymph nodes >1.0 cm in long axis diameter).
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.
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.
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 milligram per deciliter (mg/dL);
3. Total bilirubin >2.0 * institutional ULN (unless documented Gilbert's disease);
4. Uncontrolled diabetes (Hemoglobin A1c [HbA1c] >10 [percent] %) or previously undiagnosed diabetes mellitus with HbA1c >8%.
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 (example, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other significant cardiac condition (example, pericardial effusion, restrictive cardiomyopathy) within 6 months before receiving the first dose of study drug.
Has electrocardiogram (ECG) abnormalities of:
1. Q-wave infarction, unless identified 6 or more months before screening;
2. Heart rate-corrected QT interval millisecond (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.
Has congenital long QT syndrome.
Is currently using Class IA (example, quinidine, procainamide) or Class III (example, amiodarone, sotalol) antiarrhythmic medications.
Has uncontrolled hypertension despite appropriate medical therapy (sitting blood pressure [BP] of greater than 160 millimeters of mercury (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.
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).
Has received treatment with any investigational products within 3 months before the first dose of study drug.
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.
Has known gastrointestinal (GI) disease, condition or procedure that could interfere with the oral absorption or tolerance of TAK-385, including difficulty swallowing tablets.
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.
Has admission or evidence of alcohol or drug abuse or use of illicit drugs.

Name	Affiliation	Role
Medical Monitor	Millennium Pharmaceuticals, Inc.	Study Director

ID	Title	Description
FG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
FG001	Experimental: Degarelix 80 mg

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Number

participants

Title

Denominators

Categories

18 to 64 years

Title	Measurements
	BG0009 BG0017 BG00216

65 to 84 years

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0002 BG0013 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

White

Title	Measurements
	BG00058 BG00131 BG002

Eastern Cooperative Oncology Group (ECOG) Performance status

ECOG assessed participants performance status on a 6-point scale: 0: Fully active, able to carry on all predisease performance without restriction; 1: Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature; 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about greater than (>)50 percent (%) of waking hours; 3:Capable of limited selfcare,confined to bed or chair >50% of waking hours; 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair; 5:Dead.

Number

participants

Title

Denominators

Categories

Grade 0

Title	Measurements
	BG00060 BG001

Prostate Cancer Type

Number

participants

Title

Denominators

Categories

Adenocarcinoma insitu,Not otherwise specified(NOS)

Title	Measurements
	BG0005 BG0011 BG002

Primary Gleason Score

Gleason score is a histological score that, together with other clinical factors may be used to predict the potential aggressiveness of the cancer and thus its risk of eventually spreading. Gleason scores range from 2-10, where 2-4: lower risk; 5-6: moderate risk; 8-10: higher risk with lower score representing most well-differentiated tumors and higher score representing least-differentiated tumors. Primary grading in Gleason score is assigned to dominant pattern of tumor which has to be >50% of total pattern seen.

Number

participants

Title

Denominators

Categories

Primary grade 3

Title	Measurements
	BG00028 BG001

Secondary Gleason Score

Number

participants

Title

Denominators

Categories

Secondary grade 3

Title	Measurements
	BG00022 BG001

Total Gleason Score

Number

participants

Title

Denominators

Categories

Total Gleason score 6

Title	Measurements
	BG0005 BG001

Initial diagnosis of Primary Tumor (T)

TNM Stages: T1: unapparent neither palpable nor visible by imaging, T1a: histologic finding in 5% or less of tissue resected, T1b: histological finding in >5% of tissue resected, T1c: identified by needle biopsy, T2: confined within prostate, T2a: one-half of one lobe or less, T2b: involves more than one-half of one lobe but not both lobes, T2c: involves both lobes, T3: extends through prostate capsule, T3a: Extracapsular extension Including microscopic bladder neck involvement, T3b: invades seminal vesicles, T4: fixed or invades adjacent structures other than seminal vesicles

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG0002 BG001

Initial diagnosis: Regional Lymph Nodes (N)

TNM: Regional lymph nodes (N) staging included NX: Regional lymph nodes were not assessed, and N0: No regional lymph node metastasis.

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG00041 BG00118

Initial diagnosis: Distant Metastasis (M)

TNM: Distant metastasis stages included, M0: No distant metastasis.

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG00056 BG00134 BG002

Diagnosis of Primary Tumor at Study entry

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG0001 BG001

Study entry: N

TNM: Regional lymph nodes staging included NX: Regional lymph nodes were not assessed, and N0: No regional lymph node metastasis.

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG00039 BG00119 BG002

Study entry: M

TNM: Distant metastasis stages included, M0: No distant metastasis.

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG00051 BG00128 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Effective Castration Rate Over 25 Weeks

Castration rate is defined as the observed percentage of participants who have testosterone concentrations less than (<) 50 nanogram per deciliter (ng/dL) (1.73 nanomole per liter [nmol/L]) at all scheduled visits.

Safety population included all participants who received at least one dose of study medication.

Posted

Number

95% Confidence Interval

percentage of participants

Day 1 Week 5 up to Day 1 Week 25

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG00065 OG00138

Title

Denominators

Categories

Title	Measurements
	OG00095(87.1 to 99.0) OG00189(75.2 to 97.1)

Secondary

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs

Safety population included all participants who received at least one dose of study medication.

Posted

Number

participants

Baseline up to Week 29

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Number of Participants With TEAEs Related to Physical Findings

Safety population included all participants who received at least one dose of study medication.

Posted

Number

participants

Baseline up to Week 29

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Number of Participants With TEAEs Related to 12-lead Electrocardiogram (ECG) Findings

Safety population included all participants who received at least one dose of study medication.

Posted

Number

participants

Baseline up to Week 29

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Urinalysis

Safety population included all participants who received at least one dose of study medication.

Posted

Number

participants

Baseline up to Week 29

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Number of Participants Reporting One or More TEAEs and Serious Adverse Events (SAEs)

Safety population included all participants who received at least one dose of study medication.

Posted

Number

participants

Baseline up to Week 29

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Average Percent Change in Prostate Size

Percent change in prostate size was assessed at a follow up visit between Day 1 Week 9 to Day 1 Week 13.

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

percent change

Baseline, Day 1 Week 9 to Day 1 Week 13

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Time to Achieve Effective Castration

Time to effective castration is defined as days from first dose to first testosterone measurement that is <50 ng/dL.

Safety population included all participants who received at least one dose of study medication.

Posted

Median

95% Confidence Interval

days

Baseline up to Week 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Time to Achieve Profound Castration

Time to profound castration is defined as days from first dose to first testosterone measurement that is <20 ng/dL.

Safety population included all participants who received at least one dose of study medication.

Posted

Median

95% Confidence Interval

days

Baseline up to Week 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Estimated Time to Testosterone Recovery (TTR)

TTR is defined as the time from 1 day after the last dose of TAK-385 or 4 weeks plus 1 day after the last dose of degarelix to testosterone recovery. Testosterone recovery is defined as back to baseline or >280 ng/dL whichever occurs first. TTR was determined during 12 weeks after the discontinuation of androgen deprivation therapy (ADT).

Safety population included all participants who received at least one dose of study medication.

Posted

Median

95% Confidence Interval

days

Up to Day 1 Week 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants

Secondary

Percentage of Participants Who Have Recovered to Baseline Value of Testosterone

Safety population included all participants who received at least one dose of study medication.

Posted

Number

percentage of participants

Up to Day 1 Week 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Who Have Recovered to >280 ng/dL Testosterone

Safety population included all participants who received at least one dose of study medication.

Posted

Number

percentage of participants

Day 1 Week 25 up to Day 1 Week 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Number of Participants With PSA Response of >=50% and >=90% Reduction

Prostate-specific Antigen (PSA) response was defined as 50% and 90% reduction from baseline in serum PSA levels.

Safety population included all participants who received at least one dose of study medication.

Posted

Number

participants

Day 1 Week 13

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Serum PSA Concentration

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

percent change

Baseline, Day 1 of Week 2, 3 , 5, 9, 13, 17, 21, 25, 29, 33 and 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

PSA Nadir

Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

microgram per liter (mcg/L)

Baseline up to Day 1 Week 25

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Serum PSA Concentration

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

mcg/L

Day 1 of Week 13, 25, 29, 33 and 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Plasma Concentrations of TAK-385

Safety population where TAK-385 assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

Day 1 Week 1, 2, 3, 5, 9, 13, 17, 25, 33, 37: Pre-dose; Day 1 Week 5, 13: 2 hrs Post-dose; Day 4 Week 1: Pre-dose

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.

Units	Counts
Participants	OG000

Secondary

Serum Luteinizing Hormone (LH) Level

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

milli-international units per milliliter

Baseline, Day 1 of Weeks 2, 3, 5, 9, 13, 17, 21, 25, 29, and 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Serum Follicle-Stimulating Hormone (FSH) Level

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

International units per liter (IU/L)

Baseline, Day 1 of Week 2, 5, 13, 25 and 29

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Serum Sex Hormone-Binding Globulin (SHBG) Level

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

nmol/L

Baseline, Day 1 of Week 2, 5, 13, 25 and 29

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Aging Male's Symptoms (AMS) Total Scale Score

AMS scale is a self-administered questionnaire used to 1) assess symptoms of aging (independent from those that are disease related) between groups of males under different conditions; 2) evaluate the severity of symptoms over time; and 3) measure changes before and after androgen therapy. Each question was answered between none (1) to extremely severe (5) for 17 items from psychological (5 items), somatic (7 items), and sexual (5 items) categories. Total score is sum of all the item scores and range from 17 (minimum) to 85 (maximum), where high score indicated high level of symptoms.

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

percent change

Day 1 of Weeks 5, 13, 25, 29, 33 and 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Secondary

Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Score

EORTC QLQ-C30 included 30 questions comprising 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, nausea/vomiting), single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties) and a global health and QOL scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'); 2 questions used 7-point scale (1 'Very poor' to 7 'Excellent'). All domain scores were calculated as an average of item scores and transformed to 0-100 score range where a high score from 0-100 indicates: A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Least Squares Mean

Standard Error

units on scale

Baseline and last post-baseline value up to Week 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg

Secondary

Change From Baseline in 25-item Prostate Cancer-specific Questionnaire Supplement (EORTC QLQ-PR25) Score

EORTC QLQ-PR25 : EORTC module designed to supplement the QLQ-C30 for any application in prostate cancer. It Consist of 25 questions distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale, with higher scores reflecting either more symptoms (urinary, bowel, hormonal treatment-related symptoms) or higher levels of activity or functioning (sexual).

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least one dose of study medication.

Posted

Least Squares Mean

Standard Error

units on scale

Baseline and last post-baseline value up to Week 37

ID	Title	Description
OG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
OG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.

Facility	Status	City	State	ZIP	Country	Contacts
		Birmingham	Alabama		United States

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Oesophagitis ulcerative	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected65 at risk EG0011 affected38 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected65 at risk EG0011 affected38 at risk
Mesothelioma malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected65 at risk EG0011 affected38 at risk
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected65 at risk EG0010 affected38 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected65 at risk EG0011 affected38 at risk
Hypertension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected65 at risk EG0010 affected38 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hot flush	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG00037 affected65 at risk EG00123 affected38 at risk
Fatigue	General disorders	MedDRA (18.0)	Systematic Assessment	EG00017 affected65 at risk EG0016 affected38 at risk
Cataract	Eye disorders	MedDRA (18.0)	Systematic Assessment	EG00010 affected65 at risk EG0017 affected38 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00012 affected65 at risk EG0015 affected38 at risk
Nocturia	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0009 affected65 at risk EG0015 affected38 at risk
Pollakiuria	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0008 affected65 at risk EG0016 affected38 at risk
Dysuria	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0005 affected65 at risk EG0016 affected38 at risk
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0006 affected65 at risk EG0013 affected38 at risk
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0006 affected65 at risk EG0012 affected38 at risk
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected65 at risk EG0013 affected38 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0005 affected65 at risk EG0011 affected38 at risk
Blood testosterone increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0002 affected65 at risk EG0014 affected38 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected65 at risk EG0013 affected38 at risk
Micturition urgency	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0005 affected65 at risk EG0011 affected38 at risk
Nasopharyngitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0004 affected65 at risk EG0012 affected38 at risk
Sinusitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0004 affected65 at risk EG0012 affected38 at risk

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
C561634	relugolix
C431566	acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

ID	Title	Description
BG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.
BG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Experimental: TAK-385 120 mg	TAK-385 320 mg, tablets, orally, as loading dose on Day 1 followed by TAK-385 120 mg, tablets, orally, daily as maintenance dose starting from Day 2 up to Day 7 Week 24.			1	65	56	65
EG001	Experimental: Degarelix 80 mg	Degarelix 240 mg, injection, subcutaneously, on Day 1 Week 1 followed by Degarelix 80 mg, injection, subcutaneously, once every 4 weeks beginning on Day 1 Week 5 up to Day 1 Week 21.			3	38	37	38