A Study of TAK-385 in Hormone Treatment-naïve Participants With Prostate Cancer

NCT02141659 | Completed Phase 1 Results

• 2 other identifiers: TAK-385/TB-AK160108U1111-1156-6034
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the tolerability and safety of TAK-385 in hormone treatment-naïve participants with non-metastatic prostate cancer.

Conditions

Hormone Treatment-naïve Participants With Prostate Cancer

Outcome Measures

Primary Outcomes (9)

• Part A: Number of Participants With Dose-limiting Toxicities (DLTs)

  DLTs were defined as treatment-related adverse events (AEs) that occurred within the first 28 days of treatment as per common terminology criteria for adverse events (CTCAE) version 4.03: any grade 3 or higher toxicity; QT/Fridericia corrected QT (QTcF) greater than (\>) 500 millisecond (msec) after treatment initiation; QT/QTcF interval prolongation \>60 msec postdose.

  From treatment initiation until Day 28

• Part A: Number of Participants Reporting One or More Treatment-emergent Adverse Event (TEAE)

  From treatment initiation until 40 days after last dose of study drug (Day 68)

• Part A: Number of Participants With Grade 2 or Higher Laboratory Test Abnormalities

  Laboratory test abnormalities were graded using the CTCAE. The grades were: Grade 2- (moderate) minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activity of daily living (ADL); Grade 3- (severe) medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self-care ADL. Data has been presented for any Grade 2 or higher event in the laboratory test abnormalities.

  From treatment initiation until 40 days after last dose of study drug (Day 68)

• Part A: Number of Participants With Markedly Abnormal Values of Vital Signs Parameters

  From treatment initiation until 40 days after last dose of study drug (Day 68)

• Part A: Number of Participants With Markedly Abnormal Values of Electrocardiogram (ECG) Parameters

  From treatment initiation until 40 days after last dose of study drug (Day 68)

• Part B: Number of Participants Reporting One or More TEAE

  From treatment initiation until 40 days after last dose of study drug (Day 712)

• Part B: Number of Participants With Grade 2 or Higher Laboratory Test Abnormalities

  Laboratory test abnormalities were graded using the CTCAE. The grades were: Grade 2- (moderate) minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL; Grade 3- (severe) medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self-care ADL. Data has been presented for any Grade 2 or higher event in the laboratory test abnormalities. Here aspartate aminotransferase (AST) (glutamic-oxaloacetic transaminase \[GOT\]) High, creatine kinase (CK) (creatine phosphokinase \[CPK\]) High, prothrombin time (PT)-international normalized ratio (INR) High.

  From treatment initiation until 40 days after last dose of study drug (Day 712)

• Part B: Number of Participants With Markedly Abnormal Values of Vital Signs Parameters

  Here "BP" is blood pressure.

  From treatment initiation until 40 days after last dose of study drug (Day 712)

• Part B: Number of Participants With Markedly Abnormal Values of ECG Parameters

  From treatment initiation until 40 days after last dose of study drug (Day 712)

Secondary Outcomes (6)

• Part A: Cmax: Maximum Observed Plasma Concentration for Unchanged TAK-385 on Day 1, 14 and 28

  Days 1, 14 and 28 pre-dose and at multiple time points (up to 12 hours for Days 1 and 14; up to 72 hours for Day 28) post-dose

• Part A: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to (Tau) Over the Dosing Interval for Unchanged TAK-385 on Day 1, 14 and 28

  Days 1, 14 and 28 pre-dose and at multiple time points (up to 12 hours for Days 1 and 14; up to 72 hours for Day 28) post-dose

• Part A: Serum Testosterone Concentrations for TAK-385

  Up to Day 35

• Part B: Percent Change From Baseline in PSA Levels on Week 13 Day 1 Last Observation Carried Forward (LOCF)

  Baseline, and Week 13 Day 1 (LOCF; up to Week 13 Day 1)

• Part B: Plasma Concentration of Unchanged TAK-385

  Up to Week 49 Day 1

Study Arms (6)

Part A Cohort 1: TAK-385 320 mg + TAK-385 80 mg

EXPERIMENTAL

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 80 mg maintenance dose, tablet, orally, once daily through Days 2 to 28.

Drug: TAK-385

Part A Cohort 2: TAK-385 320 mg + TAK-385 120 mg

EXPERIMENTAL

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 28.

Drug: TAK-385

Part A Cohort 3: TAK-385 320 mg + TAK-385 160 mg

EXPERIMENTAL

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 160 mg maintenance dose, tablet, orally, once daily through Days 2 to 28.

Drug: TAK-385

Part A Cohort 4: TAK-385 360 mg + TAK-385 120 mg

EXPERIMENTAL

TAK-385 360 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 28.

Drug: TAK-385

Part B Cohort 1: TAK-385 320 mg + TAK-385 80 mg

EXPERIMENTAL

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 80 mg maintenance dose, tablet, orally, once daily through Days 2 to 672.

Drug: TAK-385

Part B Cohort 2: TAK-385 320 mg + TAK-385 120 mg

EXPERIMENTAL

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 672.

Drug: TAK-385

Interventions

TAK-385 DRUG

TAK-385 Tablets.

Part A Cohort 1: TAK-385 320 mg + TAK-385 80 mg; Part A Cohort 2: TAK-385 320 mg + TAK-385 120 mg; Part A Cohort 3: TAK-385 320 mg + TAK-385 160 mg; Part A Cohort 4: TAK-385 360 mg + TAK-385 120 mg; Part B Cohort 1: TAK-385 320 mg + TAK-385 80 mg; Part B Cohort 2: TAK-385 320 mg + TAK-385 120 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants judged by the investigator to have the capacity to understand the study and follow the study rules.
• Participants whose written consent (signature or printed name and personal seal on informed consent form) can be obtained before any study procedures are performed.
• Japanese male participants 20 or more years of age at the time of informed consent.
• Participants who, if they have a female partner who could become pregnant, agree to practice appropriate means of contraception from the time of informed consent throughout the entire study treatment period and for 4 months after the last dose of study drug.
• Participants in stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks (28 days) prior to study treatment initiation.
• Participants with histologically or cytologically confirmed prostate cancer.
• Participants whose clinical diagnosis is T1-4 N0 M0, or Tx N0 M0 for participants who have undergone radical prostatectomy.
• Participants who are considered eligible for hormone therapy for prostate cancer.
• Participants who have not received hormone therapy (example, gonadotropin-releasing hormone \[GnRH\] agonist, GnRH antagonist, steroidal antiandrogen, non-steroidal androgen) for prostate cancer.
• Participants who have not undergone surgical castration.
• Participants with serum testosterone at screening greater than (\>) 150 nanogram per deciliter (ng/dL).
• Participants meeting either of the following criteria for prostate-specific antigen (PSA) at screening. Untreated prostate cancer: PSA at screening \> 4.0 nanogram per milliliter (ng/mL) Treated\* prostate cancer: PSA at screening \> 0.2 ng/mL.
• Participants who have undergone prostatectomy or either or both of high intensity focused ultrasound therapy or radiotherapy (excluding 125I-brachytherapy) prior to the start of this study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status \[17\] of 0 or 1.
• Body mass index (BMI) at screening greater than or equal to (\>=) 18.0 kilogram per square meter (kg/m\^2).

You may not qualify if:

• Participants exhibiting symptoms judged related to prostate cancer by the investigator (example, bone pain, pelvic pain, ureteral obstruction) who urgently require hormone therapy such as GnRH agonist, GnRH antagonist, or CAB/MAB therapy, chemotherapy, or radiotherapy.
• Participants who have received 5-alpha reductase inhibitors (except for participants who have been treated for male-pattern alopecias).
• Participants who have received chemotherapy for prostate cancer (including estramustine).
• Participants who have received 125I-brachytherapy.
• Participants who received radiotherapy (except for 125I-brachytherapy) within 16 weeks (112 days) before study treatment initiation.
• Participants who underwent prostatectomy within 16 weeks (112 days before study treatment initiation.
• Treatment with any investigational compound within the 4 weeks (28 days) prior to the first dose of study drug or ongoing participation in another experimental trial related to the treatment of prostate cancer.
• Diagnosis or treatment for another systemic malignancy within 2 years before study treatment initiation, or who had received a diagnosis of another malignancy before that and have evidence of residual disease. Participants with non-melanoma skin cancer or carcinoma in situ who have undergone complete resection will not be excluded from the study.
• Participants taking drugs with moderate to strong cytochrome P450 3A4 (CYP3A4) inhibitory or inducing effects, or any medications, supplements, or food products with P-glycoprotein (P-gp) inhibitory effects, in the 2 weeks (14 days) prior to study treatment initiation.
• Participants who have received TAK-385 in a past clinical study.
• Participants for whom it would be difficult to collect blood from a peripheral vein.
• Participants with uncontrolled and clinically significant nervous, circulatory, pulmonary, hepatic, renal, metabolic, gastrointestinal, urogenital, or endocrine disorders, or other abnormalities (except for the targeted disease) that could affect study participation or the study results. Also, participants meeting any of criteria a through c below.
• A. Participants with uncontrolled diabetes (Hemoglobin A1c \[HbA1C\] \> 8 percent \[%\] at screening). However, participants whose HbA1c is brought under control with diabetes medications may be rescreened.
• B. Participants with uncontrolled hypertension (systolic blood pressure \> 150 millimeter of mercury (mmHg) and diastolic blood pressure \> 90 mmHg at 2 separate measurements taken no more than 60 minutes apart at screening). Participants whose blood pressure is brought under control by antihypertensive medication may be rescreened.
• C. Participants with myocardial infarction, unstable symptomatic ischemic heart disease, arrhythmias of common terminology criteria for adverse events (CTCAE) Grade \> 2, thromboembolism (deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or other heart diseases (example, pericardial effusion, restrictive cardiomyopathy). However, chronic stable atrial fibrillation controlled by stable anticoagulant therapy will be allowed.

Sponsors & Collaborators

• Takeda: lead

Study Sites (6)

Unknown Facility

Sakura-shi, Chiba, Japan

Location

Unknown Facility

Maebashi, Gunma, Japan

Location

Unknown Facility

Sapporo, Hokkaido, Japan

Location

Unknown Facility

Kanazawa, Ishikawa-ken, Japan

Location

Unknown Facility

Yokohama, Kanagawa, Japan

Location

Unknown Facility

Chiyoda-ku, Tokyo, Japan

Location

Related Publications (1)

• Suzuki H, Uemura H, Mizokami A, Hayashi N, Miyoshi Y, Nagamori S, Enomoto Y, Akaza H, Asato T, Kitagawa T, Suzuki K. Phase I trial of TAK-385 in hormone treatment-naive Japanese patients with nonmetastatic prostate cancer. Cancer Med. 2019 Oct;8(13):5891-5902. doi: 10.1002/cam4.2442. Epub 2019 Aug 19.

  PMID: 31429205 DERIVED

MeSH Terms

Interventions

relugolix

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2014
• First Posted: May 19, 2014
• Study Start: May 1, 2014
• Primary Completion: April 20, 2017
• Study Completion: April 20, 2017
• Last Updated: November 19, 2018
• Results First Posted: November 19, 2018

Record last verified: 2018-04

Locations

JP (6)