Prostate Cancer
Conditions
Keywords
Prostate cancer, TAK-700, Bicalutamide, S1216, androgen therapy, Phase III
Brief summary
The purpose of this study is to compare overall survival in newly diagnosed metastatic prostate cancer patients randomly assigned to androgen deprivation therapy (ADT) + TAK-700 versus ADT + bicalutamide.
Interventions
DRUGTAK-700
300 mg, PO, twice daily
DRUGBicalutamide
50 mg, PO, q daily
Sponsors
Millennium Pharmaceuticals, Inc.
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of metastatic prostate cancer. * Serum testosterone within institutional limits of normal. * PSA ≥ 2 ng/mL within 90 days prior to initiation of androgen deprivation. therapy (for early induction) or prior to registration (for late induction). * DEXA scan within 2 years prior to registration. * ECG within 42 days prior to registration and QTc interval ≤ 460 msec. * LVEF within 42 days prior to registration and within institutional limits of normal. * Adequate hepatic function as evidenced by bilirubin ≤ 2 x institutional upper limit of normal (ULN), SGOT (AST) and SGPT (ALT) ≤ 3 x institutional ULN, or ≤ 5 x institutional ULN if liver metastases are present. * Adequate renal function as evidenced by calculated creatinine clearance ≥ 40 mL/min. * Adequate hematologic function as evidenced by leukocytes ≥ 3,000/mcL, absolute neutrophil count (ANC) ≥ 1,500/mcL, hemoglobin ≥ 9 g/dL, and platelets ≥ 100,000/mcL. * Zubrod performance status of 0 - 2. Zubrod performance status 3 will be allowed if from bone pain only. * ≥ 18 years of age. * Men of reproduction potential and those who are surgically sterilized (i.e., postvasectomy) must agree to practice effective barrier contraception or agree to abstain from intercourse while receiving treatment on this study and for at least 4 months after protocol treatment ends.
Exclusion criteria
* Known brain metastases. * No more than 36 months of prior neoadjuvant and/or adjuvant hormonal therapy. * ≥ 6 months since completion of androgen deprivation therapy. * Prior or concurrent therapy with ketoconazole, aminoglutethimide or abiraterone acetate, or enzalutamide (MDV3100). Concurrent megestrol for hot flashes is allowed. * Prior chemotherapy for treatment of metastatic prostate cancer. Prior chemotherapy in the neoadjuvant or adjuvant setting is allowed. * ≥ 2 years since completion of chemotherapy in the neoadjuvant or adjuvant setting. * Concurrent use of experimental therapy is not allowed. * ≥ 30 days since prior medical castration for metastatic prostate cancer. * If method of castration is a LHRH agonist, the patient must be willing to continue the use of LHRH and add bicalutamide or TAK-700 during protocol treatment. * If the patient was on an antiandrogen (e.g. bicalutamide, flutamide), the patient must be willing to switch over to bicalutamide or TAK-700 (according to randomization). * Prior bilateral orchiectomy. * Concurrent use of LHRH antagonists (e.g. Degarelix) * Grade III/IV cardiac disease (as defined by the NYHA Criteria), thromboembolic event, unstable angina pectoris, myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia. * Uncontrolled hypertension (defined as blood pressure \> 160 mmHg systolic and \> 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the Screening visit) despite appropriate medical therapy. * Known human immunodeficiency virus (HIV)infection, active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study. * History of primary and secondary adrenal insufficiency. * Hypersensitivity to TAK-700, to TAK-700 metabolites, to bicalutamide, or to LHRH agonists. * Gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of TAK-700, including difficulty swallowing oral medications. * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Duration of treatment and follow-up until death or 9 years after study start | Overall survival is defined as the time from random assignment to the date of death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Duration of treatment and follow-up until death or 9 years after study start | Progression Free Survival (PFS) is defined as the time from random assignment to first documentation of PSA progression, radiologic progression, clinical progression, or death, whichever occurred first. PSA progression is defined as a ≥25% increase AND and absolute increase of at last 2 ng/mL from the nadir PSA (or from baseline PSA if there was no drop in PSA after starting treatment). Radiologic progression is defined as two or more new lesions on radionuclide bone scans. Clinical progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| PSA Response Rates | 7 months after randomization | Prostate-specific antigen (PSA) response rates were divided into complete response (CR: PSA \< 0.2 ng/mL), partial response (PR: PSA between 0.2 and 4.0 ng/mL), and no response (NR: PSA \> 4.0 ng/mL) at a 7-month landmark after random assignment. |
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duration of treatment and follow-up until death or 9 years after study start | Only adverse events that are possibly, probably or definitely related to study drug are reported. Adverse events are graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0) where grade refers to the severity of the AE. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
| Long-term Survival | After 10 years of follow-up | Long-term survival is defined as the time from random assignment to the date of death from any cause |
Countries
United States
Participant flow
Pre-assignment details
1,313 participants were enrolled and randomly assigned. 32 participants were deemed ineligible and 2 withdrew consent before starting treatment. Therefore, 1,279 were deemed eligible and analyzable for the primary analysis.
Participants by arm
| Arm | Count |
|---|---|
| LHRHa + TAK-700 Experimental: ADT + TAK-700 LHRH agonist - given as approved for androgen deprivation at a dose necessary to maintain castrate levels and equivalent to 22.5 mg of Leuprolide IM every 3 months.
TAK-700, 300 mg, PO, twice daily | 638 |
| LHRHa + Bicalutamide Active Comparator: ADT + Bicalutamide LHRH agonist - given as approved for androgen deprivation at a dose necessary to maintain castrate levels and equivalent to 22.5 mg of Leuprolide IM every 3 months.
Bicalutamide, 50 mg, PO, q daily | 641 |
| Total | 1,279 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 80 | 21 |
| Overall Study | Currently on Treatment | 192 | 100 |
| Overall Study | Death | 26 | 13 |
| Overall Study | Disease Progression | 226 | 372 |
| Overall Study | No Protocol Treatment | 10 | 11 |
| Overall Study | Other, Not Specified | 34 | 52 |
| Overall Study | Participant Refusal | 70 | 72 |
Baseline characteristics
| Characteristic | LHRHa + TAK-700 | LHRHa + Bicalutamide | Total |
|---|---|---|---|
| Age, Continuous | 67.6 years | 68.1 years | 67.8 years |
| Bisphosphonate Use at Study Entry No | 599 Participants | 606 Participants | 1205 Participants |
| Bisphosphonate Use at Study Entry Yes | 39 Participants | 35 Participants | 74 Participants |
| Bone Metastases No | 168 Participants | 159 Participants | 327 Participants |
| Bone Metastases Yes | 470 Participants | 482 Participants | 952 Participants |
| Bone Pain No | 480 Participants | 498 Participants | 978 Participants |
| Bone Pain Yes | 158 Participants | 143 Participants | 301 Participants |
| Disease Severity Extensive | 310 Participants | 313 Participants | 623 Participants |
| Disease Severity Minimal | 328 Participants | 328 Participants | 656 Participants |
| Gleason Score at Initial Diagnosis 7 | 165 Participants | 168 Participants | 333 Participants |
| Gleason Score at Initial Diagnosis < 7 | 46 Participants | 39 Participants | 85 Participants |
| Gleason Score at Initial Diagnosis 8 | 123 Participants | 118 Participants | 241 Participants |
| Gleason Score at Initial Diagnosis 9-10 | 249 Participants | 264 Participants | 513 Participants |
| Gleason Score at Initial Diagnosis Missing | 55 Participants | 52 Participants | 107 Participants |
| Liver Metastases No | 622 Participants | 627 Participants | 1249 Participants |
| Liver Metastases Yes | 16 Participants | 14 Participants | 30 Participants |
| Median PSA Level | 27.2 ng/mL | 31.8 ng/mL | 29.7 ng/mL |
| Other Visceral Metastases No | 556 Participants | 569 Participants | 1125 Participants |
| Other Visceral Metastases Yes | 82 Participants | 72 Participants | 154 Participants |
| Preregistration LHRH Suppression No | 308 Participants | 310 Participants | 618 Participants |
| Preregistration LHRH Suppression Yes | 330 Participants | 331 Participants | 661 Participants |
| Prior Bilateral Orchiectomy No | 634 Participants | 638 Participants | 1272 Participants |
| Prior Bilateral Orchiectomy Yes | 4 Participants | 3 Participants | 7 Participants |
| Prior Radical Prostatectomy No | 471 Participants | 493 Participants | 964 Participants |
| Prior Radical Prostatectomy Yes | 167 Participants | 148 Participants | 315 Participants |
| Race/Ethnicity, Customized Black | 64 Participants | 71 Participants | 135 Participants |
| Race/Ethnicity, Customized Others | 35 Participants | 32 Participants | 67 Participants |
| Race/Ethnicity, Customized White | 539 Participants | 538 Participants | 1077 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 638 Participants | 641 Participants | 1279 Participants |
| Zubrod Performance Status Score 0 | 416 Participants | 442 Participants | 858 Participants |
| Zubrod Performance Status Score 1 | 197 Participants | 175 Participants | 372 Participants |
| Zubrod Performance Status Score 2 | 21 Participants | 21 Participants | 42 Participants |
| Zubrod Performance Status Score 3 | 3 Participants | 2 Participants | 5 Participants |
| Zubrod Performance Status Score Missing | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 251 / 638 | 274 / 641 |
| other Total, other adverse events | 615 / 627 | 609 / 629 |
| serious Total, serious adverse events | 235 / 627 | 15 / 629 |
Outcome results
Primary
Overall Survival
Overall survival is defined as the time from random assignment to the date of death from any cause
Time frame: Duration of treatment and follow-up until death or 9 years after study start
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LHRHa + TAK-700 | Overall Survival | 81.1 months |
| LHRHa + Bicalutamide | Overall Survival | 70.2 months |
p-value: 0.0895% CI: [0.72, 1.02]Regression, Cox
Secondary
Long-term Survival
Long-term survival is defined as the time from random assignment to the date of death from any cause
Time frame: After 10 years of follow-up
Secondary
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Only adverse events that are possibly, probably or definitely related to study drug are reported. Adverse events are graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0) where grade refers to the severity of the AE. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Duration of treatment and follow-up until death or 9 years after study start
Population: Eligible participants who received at least one dose of protocol treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Osteoporosis | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Otitis media | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac arrest | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 3 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gynecomastia | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pancreatitis | 7 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Spinal fracture | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatobiliary disorders - Other, specify | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stroke | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Supraventricular tachycardia | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dizziness | 3 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hoarseness | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 6 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 20 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thrombotic thrombocytopenic purpura | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 11 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urostomy stenosis | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperkalemia | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ventricular fibrillation | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 9 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ventricular tachycardia | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 127 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ejection fraction decreased | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight gain | 3 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertriglyceridemia | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Musculoskeletal and connective tiss disorder - Other | 3 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 3 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary edema | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 6 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary hypertension | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypophosphatemia | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Renal calculi | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthritis | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Serum amylase increased | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fall | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 9 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute coronary syndrome | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hot flashes | 5 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adrenal insufficiency | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Investigations - Other, specify | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adult respiratory distress syndrome | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Joint infection | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Agitation | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fever | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 10 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Laryngeal edema | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 9 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial fibrillation | 8 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Allergic reaction | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Left ventricular systolic dysfunction | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anaphylaxis | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hematuria | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flank pain | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anxiety | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 5 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 5 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 7 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bone pain | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 5 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 3 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac disorders - Other, specify | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac troponin I increased | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Multi-organ failure | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest pain - cardiac | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flu like symptoms | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Concentration impairment | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Confusion | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness lower limb | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | GGT increased | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastric hemorrhage | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Death NOS | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 2 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Back pain | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 7 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocardial infarction | 5 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 10 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastric ulcer | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 5 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Encephalopathy | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperuricemia | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dysphagia | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erectile dysfunction | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 1 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions - Other | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Obesity | 0 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 34 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema limbs | 4 Participants |
| LHRHa + TAK-700 | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hip fracture | 3 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema limbs | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | GGT increased | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hot flashes | 5 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertriglyceridemia | 3 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperuricemia | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypophosphatemia | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Investigations - Other, specify | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight gain | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthritis | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 3 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial fibrillation | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Back pain | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest pain - cardiac | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Concentration impairment | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dizziness | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dysphagia | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 11 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fever | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flank pain | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastric hemorrhage | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastric ulcer | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions - Other | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gynecomastia | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hematuria | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatobiliary disorders - Other, specify | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hip fracture | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hoarseness | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 6 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperkalemia | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 28 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Joint infection | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Laryngeal edema | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Left ventricular systolic dysfunction | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Multi-organ failure | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness lower limb | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Musculoskeletal and connective tiss disorder - Other | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocardial infarction | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Obesity | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Osteoporosis | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Otitis media | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pancreatitis | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Spinal fracture | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stroke | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Supraventricular tachycardia | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 3 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thrombotic thrombocytopenic purpura | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urostomy stenosis | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ventricular fibrillation | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ventricular tachycardia | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary edema | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary hypertension | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Renal calculi | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Serum amylase increased | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute coronary syndrome | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adrenal insufficiency | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adult respiratory distress syndrome | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Agitation | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 3 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Allergic reaction | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anaphylaxis | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anxiety | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bone pain | 3 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac arrest | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac disorders - Other, specify | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac troponin I increased | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Confusion | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Death NOS | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 2 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ejection fraction decreased | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Encephalopathy | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erectile dysfunction | 4 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 1 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fall | 0 Participants |
| LHRHa + Bicalutamide | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flu like symptoms | 0 Participants |
Secondary
Progression Free Survival
Progression Free Survival (PFS) is defined as the time from random assignment to first documentation of PSA progression, radiologic progression, clinical progression, or death, whichever occurred first. PSA progression is defined as a ≥25% increase AND and absolute increase of at last 2 ng/mL from the nadir PSA (or from baseline PSA if there was no drop in PSA after starting treatment). Radiologic progression is defined as two or more new lesions on radionuclide bone scans. Clinical progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Duration of treatment and follow-up until death or 9 years after study start
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LHRHa + TAK-700 | Progression Free Survival | 47.6 months |
| LHRHa + Bicalutamide | Progression Free Survival | 23.0 months |
p-value: <0.00195% CI: [0.51, 0.67]Regression, Cox
Secondary
PSA Response Rates
Prostate-specific antigen (PSA) response rates were divided into complete response (CR: PSA \< 0.2 ng/mL), partial response (PR: PSA between 0.2 and 4.0 ng/mL), and no response (NR: PSA \> 4.0 ng/mL) at a 7-month landmark after random assignment.
Time frame: 7 months after randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LHRHa + TAK-700 | PSA Response Rates | Complete Response | 58 percentage of participants |
| LHRHa + TAK-700 | PSA Response Rates | Partial Response | 22 percentage of participants |
| LHRHa + TAK-700 | PSA Response Rates | No Response | 19 percentage of participants |
| LHRHa + Bicalutamide | PSA Response Rates | Complete Response | 44 percentage of participants |
| LHRHa + Bicalutamide | PSA Response Rates | Partial Response | 31 percentage of participants |
| LHRHa + Bicalutamide | PSA Response Rates | No Response | 25 percentage of participants |