Back to resultsStudy to Investigate the Effects of Orteronel on the QT/QTc Interval in Patients With Metastatic Castration-Resistant Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Orteronel+Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Metastatic castrate resistant prostate cancer, mCRPC, orteronel, TAK-700, Phase 2, QT, QTc
Eligibility Criteria
Inclusion Criteria:
- Voluntary written consent
- Screening PSA ≥ 2ng/ml
- Patients must have a diagnosis of mCRPC
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Prior surgical or medical castration with testosterone at screening < 50 ng/dL
Exclusion Criteria:
- Prior chemotherapy for prostate cancer within 6 months prior to screening. (Any prior therapy with cabazitaxel, mitoxantrone, or anthracyclines is exclusionary.)
- Documented central nervous system metastases
- Clinically significant heart disease
- Patients who have an abnormal 12-lead ECG result at screening including one or more of the following: QRS>110 ms, QTcF>480ms, PR interval>200 ms
- Patients who have a history of risk factors for TdP including unexplained syncope, known long QT syndrome, heart failure, angina, or clinically significant abnormal laboratory assessments
Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons
Sites / Locations
- Pinnacle Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Orteronel+Prednisone
Arm Description
Outcomes
Primary Outcome Measures
Maximum Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 1 minute) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Results of change in QTcF analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Secondary Outcome Measures
Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval
Triplicate 12-lead ECG measurements (each recording separated by approximately 1 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Bazette's formula (QTcB = QT divided by square root of RR). Results of change in QTcB, PR, QRS and uncorrected QT analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Changes From Baseline in Heart Rate
Triplicate 12-lead Electrocardiogram (ECG) measurements were performed and average was calculated. Supine heart rate was measured as beats per minute (bpm). Results of change in heart rate analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Number of Participants Reporting Change From Baseline in ECG Morphology
Participants with incidence of ECG morphology abnormalities were observed. Types of abnormalities included appearance of abnormal U waves, T waves inversion, elevation of ST segment, depression of ST segment, second or third degree heart block, right or left bundle branch block, atrial fibrillation/flutter, and myocardial infarction. New morphological changes were observed in abnormal U waves, depression of ST segment, and T waves inversion. Here, 'new' refers to change not present at baseline, ie, at any evaluation predose, and only seen postbaseline. Results of change in ECG morphology analyzed from 12-lead ECGs at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Correlation Between the QTcF Change From Baseline and Plasma Concentrations of Orteronel
Coefficient of correlation was measured using linear mixed effects model for the association between two variables; change from baseline versus the plasma concentration. Participant's effects on the intercept and plasma concentration slope were included in the model as random effects terms. Plasma concentrations were re scaled for model convergence. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
AUC(0-6): Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Postdose for Orteronel and M-I Metabolite
AUC(0-6) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau]), where tau is the length of the dosing interval - 6 hours in this study). Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Number of Participants Reporting One or More Treatment-emergent Adverse Events
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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Number of Participants Reporting Clinically Significant Abnormalities in Laboratory Values
The number of participants with any clinically significant abnormalities in safety laboratory values collected throughout study.
Number of Participants Reporting Clinically Significant Abnormalities in Vital Signs
The number of participants with any clinically significant abnormalities in vital signs collected throughout study. Vital signs included body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Number of Participants Reporting Clinically Significant Abnormalities in Physical Findings
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).
Number of Participants Reporting Clinically Significant Abnormalities in ECG
The number of participants who reported clinically significant abnormalities in ECG were measured throughout study. ECGs were performed after the participant had been supine for at least 10 minutes.
Full Information
NCT ID
NCT01549951
First Posted
March 7, 2012
Last Updated
April 24, 2016
Sponsor
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01549951
Brief Title
Study to Investigate the Effects of Orteronel on the QT/QTc Interval in Patients With Metastatic Castration-Resistant Prostate Cancer
Official Title
A Phase 2, Open-Label, Single-Arm, Multidose Study to Investigate the Effects of Orteronel on the QT/QTc Interval in Patients With Metastatic Castration-Resistant Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this phase 2, open-label, single-arm, multidose, multicenter study is to investigate the effects of Orteronel plus Prednisone on the QT/QTc interval in patients with Metastatic Castration-Resistant Prostrate Cancer
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Metastatic castrate resistant prostate cancer, mCRPC, orteronel, TAK-700, Phase 2, QT, QTc
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Orteronel+Prednisone
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Orteronel+Prednisone
Other Intervention Name(s)
TAK-700
Intervention Description
Orteronel 400-mg plus prednisone 5-mg will be administered BID orally continuously throughout the treatment cycle of the study.
Primary Outcome Measure Information:
Title
Maximum Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method
Description
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 1 minute) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Results of change in QTcF analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Time Frame
Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
Secondary Outcome Measure Information:
Title
Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval
Description
Triplicate 12-lead ECG measurements (each recording separated by approximately 1 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Bazette's formula (QTcB = QT divided by square root of RR). Results of change in QTcB, PR, QRS and uncorrected QT analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Time Frame
Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
Title
Changes From Baseline in Heart Rate
Description
Triplicate 12-lead Electrocardiogram (ECG) measurements were performed and average was calculated. Supine heart rate was measured as beats per minute (bpm). Results of change in heart rate analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Time Frame
Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
Title
Number of Participants Reporting Change From Baseline in ECG Morphology
Description
Participants with incidence of ECG morphology abnormalities were observed. Types of abnormalities included appearance of abnormal U waves, T waves inversion, elevation of ST segment, depression of ST segment, second or third degree heart block, right or left bundle branch block, atrial fibrillation/flutter, and myocardial infarction. New morphological changes were observed in abnormal U waves, depression of ST segment, and T waves inversion. Here, 'new' refers to change not present at baseline, ie, at any evaluation predose, and only seen postbaseline. Results of change in ECG morphology analyzed from 12-lead ECGs at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Time Frame
Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
Title
Correlation Between the QTcF Change From Baseline and Plasma Concentrations of Orteronel
Description
Coefficient of correlation was measured using linear mixed effects model for the association between two variables; change from baseline versus the plasma concentration. Participant's effects on the intercept and plasma concentration slope were included in the model as random effects terms. Plasma concentrations were re scaled for model convergence. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Time Frame
Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
Title
AUC(0-6): Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Postdose for Orteronel and M-I Metabolite
Description
AUC(0-6) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau]), where tau is the length of the dosing interval - 6 hours in this study). Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Time Frame
Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
Title
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite
Description
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Time Frame
Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
Title
Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite
Description
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.
Time Frame
Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
Title
Number of Participants Reporting One or More Treatment-emergent Adverse Events
Description
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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame
Baseline up to 30 days after last dose of study drug (Day 86)
Title
Number of Participants Reporting Clinically Significant Abnormalities in Laboratory Values
Description
The number of participants with any clinically significant abnormalities in safety laboratory values collected throughout study.
Time Frame
Baseline up to 30 days after last dose of study drug (Day 86)
Title
Number of Participants Reporting Clinically Significant Abnormalities in Vital Signs
Description
The number of participants with any clinically significant abnormalities in vital signs collected throughout study. Vital signs included body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Time Frame
Baseline up to 30 days after last dose of study drug (Day 86)
Title
Number of Participants Reporting Clinically Significant Abnormalities in Physical Findings
Description
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).
Time Frame
Baseline up to 30 days after last dose of study drug (Day 86)
Title
Number of Participants Reporting Clinically Significant Abnormalities in ECG
Description
The number of participants who reported clinically significant abnormalities in ECG were measured throughout study. ECGs were performed after the participant had been supine for at least 10 minutes.
Time Frame
Baseline up to 30 days after last dose of study drug (Day 86)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Voluntary written consent
Screening PSA ≥ 2ng/ml
Patients must have a diagnosis of mCRPC
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Prior surgical or medical castration with testosterone at screening < 50 ng/dL
Exclusion Criteria:
Prior chemotherapy for prostate cancer within 6 months prior to screening. (Any prior therapy with cabazitaxel, mitoxantrone, or anthracyclines is exclusionary.)
Documented central nervous system metastases
Clinically significant heart disease
Patients who have an abnormal 12-lead ECG result at screening including one or more of the following: QRS>110 ms, QTcF>480ms, PR interval>200 ms
Patients who have a history of risk factors for TdP including unexplained syncope, known long QT syndrome, heart failure, angina, or clinically significant abnormal laboratory assessments
Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Pinnacle Oncology
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study to Investigate the Effects of Orteronel on the QT/QTc Interval in Patients With Metastatic Castration-Resistant Prostate Cancer
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