Study to Investigate the Effects of Orteronel on the QT/QTc Interval in Patients With Metastatic Castration-Resistant Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01549951
First received: March 7, 2012
Last updated: April 24, 2016
Last verified: April 2016
Results First Received: February 29, 2016  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Prostate Cancer
Intervention: Drug: Orteronel+Prednisone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    Orteronel + Prednisone  
STARTED     50  
Primary Reason Off Study Treatment     50  
COMPLETED     0  
NOT COMPLETED     50  
Adverse Event                 15  
Withdrawal by Subject                 2  
Unsatisfactory therapeutic response                 1  
Progressive disease                 29  
Symptomatic deterioration                 1  
Unknown                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set was defined as all participants who received at least 1 dose of any study drug.

Reporting Groups
  Description
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.

Baseline Measures
    Orteronel + Prednisone  
Number of Participants  
[units: participants]
  50  
Age  
[units: years]
Mean (Standard Deviation)
  68.7  (8.85)  
Gender  
[units: participants]
 
Female     0  
Male     50  
Ethnicity (NIH/OMB)  
[units: participants]
 
Hispanic or Latino     1  
Not Hispanic or Latino     27  
Unknown or Not Reported     22  
Race/Ethnicity, Customized  
[units: participants]
 
White     27  
Black/African American     3  
Not reported     20  
Height  
[units: centimeters (cm)]
Mean (Standard Deviation)
  175.32  (7.521)  
Weight  
[units: kilograms (kg)]
Mean (Standard Deviation)
  87.63  (14.797)  
Eastern Cooperative Oncology Group (ECOG) performance status [1]
[units: participants]
 
0     38  
1     12  
Histological classification [2]
[units: participants]
 
Adenocarcinoma in situ, NOS     8  
Adenocarcinoma, NOS     42  
Time from initial prostate cancer diagnosis [3]
[units: years]
Mean (Standard Deviation)
  6.32  (5.325)  
[1] ECOG assessed participant's performance status on 5point scale: 0=Fully active/able to carry on all pre-disease activities without restriction;1=restricted in physically strenuous activity,ambulatory/able to carry out light or sedentary work;2=ambulatory (greater than[>] 50 percent[%] of waking hours),capable of all self care,unable to carry out any work activities;3=capable of only limited selfcare,confined to bed/chair>50% of waking hours;4=completely disabled,cannot carry on any selfcare,totally confined to bed/chair;5=dead.Participants with performance status as 0 and 1 have been reported.
[2] Carcinoma was classified as adenocarcinoma in situ (local), not otherwise specified (NOS) and adenocarcinoma, NOS.
[3] Time from initial diagnosis was defined as (first dose date – initial diagnosis date + 1) / 365.25.



  Outcome Measures
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1.  Primary:   Maximum Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method   [ 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 ]

2.  Secondary:   Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval   [ 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 ]

3.  Secondary:   Changes From Baseline in Heart Rate   [ 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 ]

4.  Secondary:   Number of Participants Reporting Change From Baseline in ECG Morphology   [ 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 ]

5.  Secondary:   Correlation Between the QTcF Change From Baseline and Plasma Concentrations of Orteronel   [ 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 ]

6.  Secondary:   AUC(0-6): Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Postdose for Orteronel and M-I Metabolite   [ 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 ]

7.  Secondary:   Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite   [ 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 ]

8.  Secondary:   Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite   [ 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 ]

9.  Secondary:   Number of Participants Reporting One or More Treatment-emergent Adverse Events   [ Time Frame: Baseline up to 30 days after last dose of study drug (Day 86) ]

10.  Secondary:   Number of Participants Reporting Clinically Significant Abnormalities in Laboratory Values   [ Time Frame: Baseline up to 30 days after last dose of study drug (Day 86) ]

11.  Secondary:   Number of Participants Reporting Clinically Significant Abnormalities in Vital Signs   [ Time Frame: Baseline up to 30 days after last dose of study drug (Day 86) ]

12.  Secondary:   Number of Participants Reporting Clinically Significant Abnormalities in Physical Findings   [ Time Frame: Baseline up to 30 days after last dose of study drug (Day 86) ]

13.  Secondary:   Number of Participants Reporting Clinically Significant Abnormalities in ECG   [ Time Frame: Baseline up to 30 days after last dose of study drug (Day 86) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Director
Organization: Takeda
phone: +1-866-835-2233
e-mail: GlobalOncologyMedinfo@takeda.com



Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01549951     History of Changes
Other Study ID Numbers: C21012
2012-000136-26 ( EudraCT Number )
U1111-1179-5656 ( Registry Identifier: WHO )
Study First Received: March 7, 2012
Results First Received: February 29, 2016
Last Updated: April 24, 2016
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency