A Phase 2 Study to Evaluate the Safety and Efficacy of TAK-385, Together With a Leuprorelin Observational Cohort, in Participants With Prostate Cancer

Vital signs included oral temperature, pulse rate, supine systolic and diastolic blood pressure, standing systolic and diastolic blood pressure, and weight. Any TEAEs that were associated with vital signs were reported.

Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10) including slit lamp examination of the anterior eye. Any TEAEs Related to physical examination were reported.

A single 12-lead ECG was performed. ECGs were read and interpreted locally and reviewed if indicated by the study monitor. ECG abnormalities were reported as AEs.

Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is any AE that results in death, is life threatening, requires hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event.

PSA Response is defined as a reduction in PSA from Baseline and is reported for 2 categories: ≥ 50% reduction and ≥ 90% reduction.

PSA nadir is the lowest PSA achieved after treatment.

Blood was collected and serum concentrations of PSA were obtained using a validated laboratory test at a central laboratory facility.

Blood was collected and serum concentrations of LH in milli international units per milliliters (mIU/mL) were obtained using a validated laboratory test at a central laboratory facility.

Blood was collected and serum concentrations of FSH were obtained using a validated laboratory test at a central laboratory facility.

Blood was collected and serum concentrations of SHBG were obtained using a validated laboratory test at a central laboratory facility.

EORTC QLQ-PR25 is an EORTC module designed to supplement the QLQ-C30 for any application in prostate cancer consisting 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 use are answered using a 4-point scale: 1=Not at all to 4 =Very much. All raw domain scores are linearly transformed to a 0 to 100 scale, with higher scores reflecting either more symptoms (urinary, bowel, hormonal treatment-related symptoms) or higher levels of activity or functioning (sexual). A positive change from Baseline in activity or functioning scales and negative change from Baseline in symptom scales indicates improvement.

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 1=none to 5=extremely severe 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.

The 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 a 4-point scale (1=Not at all to 4=Very much); 2 questions used a 7-point scale (1= Very poor to 7=Excellent). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. 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. A positive change from Baseline in quality og life or functioning scales and negative change from Baseline in symptom or difficulties scales indicates improvement.