A Phase 2 Study to Evaluate the Safety and Efficacy of TAK-385, Together With a Leuprorelin Observational Cohort, in Participants With Prostate Cancer
- Registration Number
- NCT02083185
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief Summary
The purpose of this study is to evaluate the efficacy of TAK 385 for achieving and maintaining testosterone suppression (\<50 ng/dL).
- Detailed Description
The drug being tested in this study is called relugolix (TAK-385). Relugolix is being tested to treat people who have prostate cancer. This study will look at achieving and maintaining testosterone suppression (\<50 ng/dL).
The study enrolled 136 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):
* Relugolix 80 mg
* Relugolix 120 mg
* Leuprorelin 22.5 mg
Relugolix was administered starting with a 320 mg (loading dose), followed by relugolix 80 mg or 120 mg tablets, for 48 weeks plus an optional 48-week extension at the investigator's discretion. Patients randomized to leuprorelin were administered 22.5 mg subcutaneously on Day 1 and every 12 weeks for 4 injections.
This multicenter trial was conducted in the United States and Canada. The overall time to participate in this study was 114.4 weeks. Participants made multiple visits to the clinic and at 12 weeks after last dose of study drug for a follow-up assessment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 136
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Leuprorelin 22.5 mg Leuprorelin Leuprorelin 22.5 mg, subcutaneous, injection on Day 1 and every 12 Weeks for up to 4 injections (48 weeks). Relugolix 80 mg Relugolix Relugolix 320 mg (loading dose), tablets, orally, on Day 1 followed by relugolix 80 mg, tablets, orally, once daily for 48 weeks plus an optional 48 week extension at the investigator's discretion. Relugolix 120 mg Relugolix Relugolix 320 mg (loading dose), tablets, orally, on Day 1 followed by relugolix 120 mg, tablets, orally, once daily for 48 weeks plus an optional 48 week extension at the investigator's discretion.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Effective Castration Rate Over 24 Weeks Day 1 of Week 5 to Day 1 of Week 25 Effective 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 beginning after 4 weeks of treatment.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks 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.
Number of Participants With TEAES Related to Clinical Laboratory Test Results From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks 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.
Number of Participants With TEAEs Related to Physical Examination From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks 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.
Number of Participants With TEAEs Related to 12-lead Electrocardiogram (ECG) Findings From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks 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.
Percentage of Participants With Prostate-Specific Antigen (PSA) Response of ≥ 50% and ≥ 90% Reduction at 4 Weeks Week 5, Day 1 PSA Response is defined as a reduction in PSA from Baseline and is reported for 2 categories: ≥ 50% reduction and ≥ 90% reduction.
Serum Prostate-Specific Antigen Concentration at the End of Weeks 12 and 24 Day 1 of Weeks 13 and 25 Blood was collected and serum concentrations of PSA were obtained using a validated laboratory test at a central laboratory facility.
Time to Achieve Testosterone Concentrations < 50 ng/dL and < 20 ng/dL During Weeks 1 to 24 TAK-385 Plasma Concentrations Day 1 of Weeks 1, 2, 3, 5, 9, 13, 17, 25, 37, 49 pre-dose; Day 4 of Week 1 pre-dose; Day 1 of Weeks 5, 13, 2 hrs post-dose Serum Follicle Stimulating Hormone (FSH) Concentrations Day 1 of Weeks 2, 5, 13, 25, 49, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks) Blood was collected and serum concentrations of FSH were obtained using a validated laboratory test at a central laboratory facility.
Percent Change From Baseline of Aging Male Survey (AMS) Total Score Baseline and Day 1 of Weeks 5,13, 25, 37 and 49, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks) 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.
Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks 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.
Prostate-Specific Antigen Nadir During Weeks 1 to 24 PSA nadir is the lowest PSA achieved after treatment.
Change From Baseline in EORTC QLQ-C30 Day 1 of Weeks 5, 13, 25, 37, 49, 73, 97, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks) 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.
Serum Luteinizing Hormone (LH) Concentrations Baseline and Day 4 of Week 1, Day 1 of Weeks 2, 3, 5,13, 25 and 49, End of Treatment (EOT - 106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks) 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.
Serum Sex Hormone-binding Globulin (SHBG) Concentrations Day 1 of Weeks 2, 5, 13, 25, 49, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks) Blood was collected and serum concentrations of SHBG were obtained using a validated laboratory test at a central laboratory facility.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-P25 Score Baseline and Day 1 of Weeks 5,13, 25, 37 and 49, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks) 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.