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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

NCTNCT02135445 (opens ClinicalTrials.gov in a new tab)Other idC27003 Merge to TakedaOther idU1111-1152-9537Other id2013-005002-53Other id14/LO/1052

Overview

Status
Completed
Phase
Phase 2
Enrollment
103 participants (actual)
Sponsor
Millennium Pharmaceuticals, Inc. · Industry
Design
Randomized · Open label (no masking)
Countries
2 countries

United States, United Kingdom

Start
Jun 2014
Primary completion
Dec 2015
Completion
Dec 2015
First posted
12 May 2014 (estimated)
Last update posted
13 Apr 2017
Conditions
Prostate Cancer

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201420152016
  1. Ph 2

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

    NCT02135445

    Jun 2014 to Dec 2015

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study is to evaluate the efficacy of TAK-385 for achieving and maintaining testosterone suppression.

Interventions

  • TAK-385Drug
  • DegarelixDrug

Arms2

  • Experimental

    TAK-385

    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.

  • Active comparator

    Degarelix

    Degarelix 240 mg, injection, subcutaneous, on Day 1, followed by degarelix 80 mg, injection, subcutaneous, once every four weeks, for 24 weeks.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percentage of Participants With Effective Castration Rate Over 25 Weeks

    Time frame · Day 1 Week 5 up to Day 1 Week 25

    Registry description

    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.

Secondary outcomes(20)
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs

    Time frame · Baseline up to Week 29

  2. Number of Participants With TEAEs Related to Physical Findings

    Time frame · Baseline up to Week 29

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

    Time frame · Baseline up to Week 29

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

    Time frame · Baseline up to Week 29

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

    Time frame · Baseline up to Week 29

  6. Average Percent Change in Prostate Size

    Time frame · Baseline, Day 1 Week 9 to Day 1 Week 13

    Registry description

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

  7. Time to Achieve Effective Castration

    Time frame · Baseline up to Week 37

    Registry description

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

  8. Time to Achieve Profound Castration

    Time frame · Baseline up to Week 37

    Registry description

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

  9. Estimated Time to Testosterone Recovery (TTR)

    Time frame · Up to Day 1 Week 37

    Registry description

    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).

  10. Percentage of Participants Who Have Recovered to Baseline Value of Testosterone

    Time frame · Up to Day 1 Week 37

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

    Time frame · Day 1 Week 25 up to Day 1 Week 37

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

    Time frame · Day 1 Week 13

    Registry description

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

  13. Percent Change From Baseline in Serum PSA Concentration

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

  14. PSA Nadir

    Time frame · Baseline up to Day 1 Week 25

  15. Serum PSA Concentration

    Time frame · Day 1 of Week 13, 25, 29, 33 and 37

  16. Plasma Concentrations of TAK-385

    Time frame · 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

  17. Serum Luteinizing Hormone (LH) Level

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

  18. Serum Follicle-Stimulating Hormone (FSH) Level

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

  19. Serum Sex Hormone-Binding Globulin (SHBG) Level

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

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

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

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· Day 1 Week 5 up to Day 1 Week 25

Percentage of Participants With Effective Castration Rate Over 25 Weeks

GroupValue (percentage of participants)
Experimental: TAK-385 120 mg95
Experimental: Degarelix 80 mg89
Secondary and other outcome results(7)
Secondary outcomeNumber· Baseline up to Week 29

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

GroupValue (participants)
Experimental: TAK-385 120 mg2
Experimental: Degarelix 80 mg1
Secondary outcomeNumber· Baseline up to Week 29

Number of Participants With TEAEs Related to Physical Findings

GroupValue (participants)
Experimental: TAK-385 120 mg5
Experimental: Degarelix 80 mg1
Secondary outcomeNumber· Baseline up to Week 29

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

GroupValue (participants)
Experimental: TAK-385 120 mg1
Experimental: Degarelix 80 mg1
Secondary outcomeNumber· Baseline up to Week 29

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

GroupValue (participants)
Experimental: TAK-385 120 mg0
Experimental: Degarelix 80 mg6
Secondary outcomeNumber· Baseline up to Week 29

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

GroupValue (participants)
Experimental: TAK-385 120 mg56
Experimental: Degarelix 80 mg37
Secondary outcomeMean· Baseline, Day 1 Week 9 to Day 1 Week 13

Average Percent Change in Prostate Size

GroupValue (percent change)Spread
Experimental: TAK-385 120 mg-25.120.03
Experimental: Degarelix 80 mg-27.225.88
Secondary outcomeMedian· Baseline up to Week 37

Time to Achieve Effective Castration

GroupValue (days)
Experimental: TAK-385 120 mg4
Experimental: Degarelix 80 mg3

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Experimental: TAK-385 120 mgTAK-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 / 6556 / 65
Experimental: Degarelix 80 mgDegarelix 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 / 3837 / 38

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Male
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. Is male, 18 years of age or older. 2. Has histologically confirmed diagnosis of localized prostate adenocarcinoma of intermediate risk for which 6-month neoadjuvant and adjuvant androgen deprivation therapy (ADT) to 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). 3. Is scheduled for EBRT to begin greater than or equal to (\>=) 12 weeks after the Baseline visit. 4. Has serum testosterone at screening greater then (\>) 150 nanogram per deciliter (ng/dL) (5.2 nanomoles per liter \[nmol/L\]). 5. Has screening serum PSA concentration \>2 ng/mL. 6. Has body mass index (BMI) \>=18.0 at screening or baseline. 7. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening or baseline. 8. Is a male participant, even if surgically sterilized (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.). 9. Has given voluntary written consent before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care. 10. Has suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) and pharmacodynamic sampling. Exclusion Criteria: 1. Has metastatic disease (based on investigator evaluation and assuming no likely metastatic pelvic lymph nodes \>1.0 cm in long axis diameter). 2. Had prior or current use of a gonadotropin-releasing hormone (GnRH) analog or androgen receptor antagonist as first-line hormone therapy, unless total use was less than 6 months and not more recently than 1 year before the planned baseline visit. 3. Had diagnosis of or treatment for another malignancy within 2 years before the first dose of study drug, or previous diagnosis of another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 4. Has abnormal screening and/or baseline laboratory values that suggest a clinically significant underlying disease, or the following laboratory values: 1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 \* institutional upper limit of the normal range (ULN); 2. Serum creatinine \>2.0 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%. 5. Has history of myocardial infarction, unstable symptomatic ischemic heart disease, any ongoing cardiac arrhythmias of Grade \>2 (chronic stable atrial fibrillation on stable anticoagulant therapy is allowed), thromboembolic events (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. 6. 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. 7. Has congenital long QT syndrome. 8. Is currently using Class IA (example, quinidine, procainamide) or Class III (example, amiodarone, sotalol) antiarrhythmic medications. 9. 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. 10. Has known, previously diagnosed human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illness unrelated to prostate cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study. Specific screening for chronic viral illness is at the discretion of the site and/or local institutional review board (IRB). 11. Has received treatment with any investigational products within 3 months before the first dose of study drug. 12. Is a primary family member (spouse, parent, child, or sibling) of anyone involved in the conduct of the study or is a study site employee. 13. Has known gastrointestinal (GI) disease, condition or procedure that could interfere with the oral absorption or tolerance of TAK-385, including difficulty swallowing tablets. 14. Is using any medication or food products listed in the excluded medications and dietary products table within 2 weeks before the first dose of study drug. This list includes moderate and strong inhibitors or inducers of cytochrome P450 (CYP3A4/5) and P-glycoprotein (P-gp). Participants must have no history of amiodarone use in the 6 months before the first dose of TAK-385. 15. Has admission or evidence of alcohol or drug abuse or use of illicit drugs.

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