Prostate Cancer
Conditions
Keywords
Metastatic castrate resistant prostate cancer, mCRPC, orteronel, TAK-700, Phase 2, QT, QTc
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
Interventions
DRUGOrteronel+Prednisone
Orteronel 400-mg plus prednisone 5-mg will be administered BID orally continuously throughout the treatment cycle of the study.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in Heart Rate | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval | 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 | 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. |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events | Baseline up to 30 days after last dose of study drug (Day 86) | 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 | Baseline up to 30 days after last dose of study drug (Day 86) | 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 | Baseline up to 30 days after last dose of study drug (Day 86) | 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 | Baseline up to 30 days after last dose of study drug (Day 86) | 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 | Baseline up to 30 days after last dose of study drug (Day 86) | 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. |
| Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite | 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 | 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. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 16 investigative sites in Canada, France, Greece, Ireland, Romania, and the United States from 29 May 2012 to 21 January 2015.
Pre-assignment details
Male participants with a historical diagnosis of metastatic castration-resistant prostate cancer (mCRPC) were enrolled in this single arm study to receive orteronel 400 milligram (mg) along with prednisone 5 mg twice daily for 28 days in each treatment cycle.
Participants by arm
| Arm | Count |
|---|---|
| Orteronel + Prednisone Orteronel 400 mg, tablets, orally, twice daily along with prednisone 5 mg, tablets, orally, twice daily for 2 treatment cycles of 28 days each. Gonadotropin-releasing hormone analogue therapy was supplied as a commercially available dosage formulation. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 15 |
| Overall Study | Other | 2 |
| Overall Study | Progressive disease | 29 |
| Overall Study | Symptomatic deterioration | 1 |
| Overall Study | Unsatisfactory therapeutic response | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Orteronel + Prednisone |
|---|---|
| Age, Continuous | 68.7 years STANDARD_DEVIATION 8.85 |
| Eastern Cooperative Oncology Group (ECOG) performance status 0 | 38 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 1 | 12 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 22 Participants |
| Height | 175.32 centimeters (cm) STANDARD_DEVIATION 7.521 |
| Histological classification Adenocarcinoma in situ, NOS | 8 participants |
| Histological classification Adenocarcinoma, NOS | 42 participants |
| Race/Ethnicity, Customized Black/African American | 3 participants |
| Race/Ethnicity, Customized Not reported | 20 participants |
| Race/Ethnicity, Customized White | 27 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 50 Participants |
| Time from initial prostate cancer diagnosis | 6.32 years STANDARD_DEVIATION 5.325 |
| Weight | 87.63 kilograms (kg) STANDARD_DEVIATION 14.797 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 48 / 50 |
| serious Total, serious adverse events | 17 / 50 |
Outcome results
Primary
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.
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
Population: ECG analysis population was defined as all participants with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orteronel + Prednisone | Maximum Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method | -1.4 millisecond (msec) | Standard Deviation 19.64 |
Secondary
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.
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
Population: Pharmacokinetic (PK) population was defined as all participants who had sufficient dosing data and plasma concentration-time data to permit calculations of PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Orteronel + Prednisone | AUC(0-6): Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Postdose for Orteronel and M-I Metabolite | Cycle 1 Day 1 (n=50) | 7570.4 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 3673.31 |
| Orteronel + Prednisone | AUC(0-6): Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Postdose for Orteronel and M-I Metabolite | Cycle 2 Day 1 (n=44) | 12971.6 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 6071.18 |
Secondary
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.
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
Population: ECG analysis population was defined as all participants with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orteronel + Prednisone | Changes From Baseline in Heart Rate | 5.7 bpm | Standard Deviation 8 |
Secondary
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.
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
Population: PK population was defined as all participants who had sufficient dosing data and plasma concentration-time data to permit calculations of PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Orteronel + Prednisone | Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite | Orteronel: Cycle 1 Day 1 (n=50) | 1904.0 nanogram per milliliter (ng/mL) | Standard Deviation 1000.98 |
| Orteronel + Prednisone | Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite | Orteronel: Cycle 2 Day 1 (n=44) | 3017.9 nanogram per milliliter (ng/mL) | Standard Deviation 1512.33 |
| Orteronel + Prednisone | Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite | M-I metabolite: Cycle 1 Day 1 (n=50) | 263.5 nanogram per milliliter (ng/mL) | Standard Deviation 161.22 |
| Orteronel + Prednisone | Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite | M-I metabolite: Cycle 2 Day 1 (n=44) | 597.5 nanogram per milliliter (ng/mL) | Standard Deviation 333.39 |
Secondary
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.
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
Population: ECG analysis population was defined as all participants with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Orteronel + Prednisone | Correlation Between the QTcF Change From Baseline and Plasma Concentrations of Orteronel | -0.002603 correlation coefficient | Standard Error 0.001053 |
Secondary
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.
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
Population: ECG analysis population was defined as all participants with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Orteronel + Prednisone | Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval | Uncorrected QT Interval (N=48) | -12.5 msec | Standard Deviation 17 |
| Orteronel + Prednisone | Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval | QTcB Interval (N=43) | 9.7 msec | Standard Deviation 22.61 |
| Orteronel + Prednisone | Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval | PR Interval (N=48) | -4.2 msec | Standard Deviation 7.4 |
| Orteronel + Prednisone | Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval | QRS Interval (N=48) | -1.0 msec | Standard Deviation 2.8 |
Secondary
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.
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
Population: ECG analysis population was defined as all participants with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Orteronel + Prednisone | Number of Participants Reporting Change From Baseline in ECG Morphology | Abnormal U waves | 1 participant |
| Orteronel + Prednisone | Number of Participants Reporting Change From Baseline in ECG Morphology | ST segment depression | 8 participant |
| Orteronel + Prednisone | Number of Participants Reporting Change From Baseline in ECG Morphology | T-wave inversion | 3 participant |
Secondary
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.
Time frame: Baseline up to 30 days after last dose of study drug (Day 86)
Population: Safety analysis set was defined as all participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Orteronel + Prednisone | Number of Participants Reporting Clinically Significant Abnormalities in ECG | 0 participants |
Secondary
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.
Time frame: Baseline up to 30 days after last dose of study drug (Day 86)
Population: Safety analysis set was defined as all participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Orteronel + Prednisone | Number of Participants Reporting Clinically Significant Abnormalities in Laboratory Values | 5 participants |
Secondary
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).
Time frame: Baseline up to 30 days after last dose of study drug (Day 86)
Population: Safety analysis set was defined as all participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Orteronel + Prednisone | Number of Participants Reporting Clinically Significant Abnormalities in Physical Findings | 0 participants |
Secondary
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).
Time frame: Baseline up to 30 days after last dose of study drug (Day 86)
Population: Safety analysis set was defined as all participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Orteronel + Prednisone | Number of Participants Reporting Clinically Significant Abnormalities in Vital Signs | 0 participants |
Secondary
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.
Time frame: Baseline up to 30 days after last dose of study drug (Day 86)
Population: Safety analysis set was defined as all participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Orteronel + Prednisone | Number of Participants Reporting One or More Treatment-emergent Adverse Events | 48 participants |
Secondary
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.
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
Population: PK population was defined as all participants who had sufficient dosing data and plasma concentration-time data to permit calculations of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Orteronel + Prednisone | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite | Orteronel: Cycle 2 Day 1 (n=44) | 1.6 hours |
| Orteronel + Prednisone | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite | M-I metabolite: Cycle 1 Day 1 (n=50) | 4.5 hours |
| Orteronel + Prednisone | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite | Orteronel: Cycle 1 Day 1 (n=50) | 2.0 hours |
| Orteronel + Prednisone | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite | M-I metabolite: Cycle 2 Day 1 (n=44) | 3.0 hours |