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Study in Japan and Ex-Japan to Characterize the Pharmacokinetic and Pharmacodynamic Response to Orteronel (TAK-700) in Chemotherapy-Naive Participants With Castration-Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT01666314
Recruitment Status : Completed
First Posted : August 16, 2012
Results First Posted : March 20, 2018
Last Update Posted : March 20, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Prostate Cancer
Interventions: Drug: Orteronel
Drug: Orteronel Placebo
Drug: Prednisone

  Participant Flow

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 43 investigative sites in Japan, United States, Greece, Australia, Netherlands, Ireland and United Kingdom from 20 August 2012 to 01 September 2016.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Male participants with a diagnosis of adenocarcinoma of the prostate were enrolled in the study. In Japan, participants were randomized to 200 mg orteronel, Placebo, 300 mg orteronel, or Placebo, BID, in a ratio of 2:1:2:1; ex-Japan participants were randomized to 200 mg orteronel, Placebo, 400 mg orteronel, or Placebo, BID, in a ratio of 2:1:2:1.

Reporting Groups
  Description
Placebo + Orteronel 200 mg (Japan) Orteronel placebo-matching tablets or Orteronel 200 mg, tablets, orally, twice daily (BID) in Cycle 1 (28 days) followed by orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 3 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily continuously throughout the study.
Placebo + Orteronel 300 mg (Japan) Orteronel placebo-matching tablets or Orteronel 300 mg, tablets, orally, twice daily in Cycle 1 followed by orteronel 300 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 2.8 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Placebo + Orteronel 200 mg (Ex-Japan) Orteronel placebo-matching tablets, or Orteronel 200 mg, tablets, orally, twice daily in Cycle 1 followed by orteronel 200 mg, tablets, orally, twice daily in 28 day cycles outside of Japan (Ex-Japan) for up to 3.1 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Placebo + Orteronel 400 mg (Ex-Japan) Orteronel placebo-matching tablets, or Orteronel 400 mg, tablets, orally, twice daily in Cycle 1 followed by orteronel 400 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 3.1 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Participant Flow:   Overall Study
    Placebo + Orteronel 200 mg (Japan)   Placebo + Orteronel 300 mg (Japan)   Placebo + Orteronel 200 mg (Ex-Japan)   Placebo + Orteronel 400 mg (Ex-Japan)
STARTED   33   32   36   36 
COMPLETED   0   0   0   0 
NOT COMPLETED   33   32   36   36 
Adverse Event                3                13                7                7 
Progressive Disease                11                9                19                20 
Symptomatic Deterioration                1                0                2                0 
Unsatisfactory Therapeutic Response                7                2                1                1 
Withdrawal by Subject                1                1                2                3 
Reason not Specified                10                7                5                5 



  Baseline Characteristics

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.
Data for baseline characteristics has been summarized as per the treatment received in Cycle 1.

Reporting Groups
  Description
Placebo + Orteronel 200 mg (Japan) Orteronel placebo-matching tablets, orally, twice daily (BID) in Cycle 1 (28 days) followed by orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 3 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily continuously throughout the study.
Orteronel 200 mg (Japan) Orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 3 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Placebo + Orteronel 300 mg (Japan) Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 followed by orteronel 300 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 2.8 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Orteronel 300 mg (Japan) Orteronel 300 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 2.8 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Placebo + Orteronel 200 mg (Ex-Japan) Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 followed by orteronel 200 mg, tablets, orally, twice daily in 28 day cycles outside of Japan (Ex-Japan) for up to 3.1 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Orteronel 200 mg (Ex-Japan) Orteronel 200 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 3.1 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Placebo + Orteronel 400 mg (Ex-Japan) Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 followed by orteronel 400 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 3.1 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Orteronel 400 mg (Ex-Japan) Orteronel 400 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 3.1 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.
Total Total of all reporting groups

Baseline Measures
   Placebo + Orteronel 200 mg (Japan)   Orteronel 200 mg (Japan)   Placebo + Orteronel 300 mg (Japan)   Orteronel 300 mg (Japan)   Placebo + Orteronel 200 mg (Ex-Japan)   Orteronel 200 mg (Ex-Japan)   Placebo + Orteronel 400 mg (Ex-Japan)   Orteronel 400 mg (Ex-Japan)   Total 
Overall Participants Analyzed 
[Units: Participants]
 11   22   10   22   11   25   12   24   137 
Age 
[Units: Years]
Mean (Full Range)
 72.1 
 (62 to 84) 
 68.5 
 (52 to 82) 
 70.1 
 (59 to 76) 
 71.5 
 (51 to 85) 
 69.6 
 (51 to 85) 
 69.9 
 (55 to 84) 
 73.3 
 (60 to 84) 
 69.4 
 (49 to 88) 
 70.6 
 (49 to 88) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
                 
Female      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Male      11 100.0%      22 100.0%      10 100.0%      22 100.0%      11 100.0%      25 100.0%      12 100.0%      24 100.0%      137 100.0% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
                 
Hispanic or Latino      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      1   4.2%      1   0.7% 
Not Hispanic or Latino      11 100.0%      22 100.0%      10 100.0%      22 100.0%      11 100.0%      25 100.0%      12 100.0%      23  95.8%      136  99.3% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Race/Ethnicity, Customized 
[Units: Participants]
                 
White   0   0   0   0   11   25   11   23   70 
Black or African American   0   0   0   0   0   0   1   1   2 
Asian - Japanese   11   22   10   22   0   0   0   0   65 
Region of Enrollment 
[Units: Participants]
                 
Japan   11   22   10   22   0   0   0   0   65 
Australia   0   0   0   0   3   1   2   2   8 
Greece   0   0   0   0   2   4   1   3   10 
Ireland   0   0   0   0   2   5   3   3   13 
Netherlands   0   0   0   0   1   6   1   5   13 
United Kingdom   0   0   0   0   1   0   1   1   3 
United States   0   0   0   0   2   9   4   10   25 
Height 
[Units: Cm]
Mean (Full Range)
 161.94 
 (153.0 to 168.2) 
 167.10 
 (154.0 to 177.5) 
 163.92 
 (156.6 to 170.7) 
 164.71 
 (151.0 to 174.0) 
 170.41 
 (157.0 to 184.7) 
 174.79 
 (162.0 to 186.0) 
 176.70 
 (165.0 to 185.4) 
 174.74 
 (162.0 to 189.0) 
 169.29 
 (151.0 to 189.0) 
Weight 
[Units: Kg]
Mean (Full Range)
 65.82 
 (55.1 to 82.4) 
 70.32 
 (47.5 to 85.2) 
 65.75 
 (55.5 to 76.0) 
 64.49 
 (44.7 to 87.1) 
 87.34 
 (67.0 to 113.0) 
 90.39 
 (64.0 to 130.7) 
 88.23 
 (64.9 to 114.1) 
 89.85 
 (63.0 to 134.6) 
 77.77 
 (44.7 to 134.6) 
Body Mass Index (BMI) 
[Units: Kg/m^2]
Mean (Full Range)
 25.05 
 (20.6 to 30.4) 
 25.21 
 (17.8 to 31.2) 
 24.43 
 (21.1 to 28.7) 
 23.73 
 (16.7 to 32.0) 
 29.85 
 (23.8 to 37.8) 
 29.61 
 (22.1 to 40.3) 
 28.37 
 (18.9 to 39.9) 
 29.40 
 (22.9 to 40.2) 
 26.96 
 (16.7 to 40.3) 


  Outcome Measures

1.  Primary:   Percentage of Participants With Serum Testosterone Levels Reduced to ≤ 2 ng/dL After 4 Weeks of Treatment in Japan   [ Time Frame: Baseline and Week 4 ]

2.  Secondary:   Percentage of Participants With Serum Testosterone Levels Reduced to ≤ 2 ng/dL in Ex-Japan   [ Time Frame: Baseline and Week 4 ]

3.  Secondary:   Percent Change From Baseline in Serum Testosterone Level After 4 Weeks of Treatment   [ Time Frame: Baseline and Week 4 ]

4.  Secondary:   Percent Change From Baseline in Serum Testosterone Level After 12 Weeks of Treatment   [ Time Frame: Baseline and Week 12 ]

5.  Secondary:   Percentage of Participants With Prostate-Specific Antigen Reduction ≥ 50% (PSA50) After 4 Weeks of Treatment   [ Time Frame: Baseline and Week 4 ]

6.  Secondary:   Percentage of Participants With PSA50 After 12 Weeks of Treatment   [ Time Frame: Baseline and Week 12 ]

7.  Secondary:   Absolute Values for Testosterone   [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ]

8.  Secondary:   Absolute Values for Dehydroepiandrosterone Sulfate (DHEA-S)   [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ]

9.  Secondary:   Absolute Values for Adrenocorticotropic Hormone (ACTH)   [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ]

10.  Secondary:   Absolute Values for Corticosterone   [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ]

11.  Secondary:   Absolute Values for Cortisol   [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ]

12.  Secondary:   Absolute Values for Prostate-Specific Antigen (PSA)   [ Time Frame: Baseline and Cycle 2 Day 1 ]

13.  Secondary:   Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite   [ Time Frame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ]

14.  Secondary:   AUC(0-12): Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours Post-dose for Orteronel and M-I Metabolite   [ Time Frame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ]

15.  Secondary:   Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite   [ Time Frame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ]

16.  Secondary:   AE (0-24) Cumulative Amount of Drug Excreted Into the Urine for Orteronel and MI-Metabolite   [ Time Frame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ]

17.  Secondary:   Cmax,ss: Maximum Observed Plasma Concentration at Steady State for Orteronel and MI-Metabolite   [ Time Frame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ]

18.  Secondary:   Tmax,ss: Time to Reach the Maximum Plasma Concentration (Cmax), Equal to Time (Hours) to Cmax at Steady State for Orteronel and M-I Metabolite   [ Time Frame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ]

19.  Secondary:   AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Orteronel and M-I Metabolite   [ Time Frame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ]

20.  Secondary:   Rac: Accumulation Index for Orteronel and M-I Metabolite   [ Time Frame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ]

21.  Secondary:   Ctrough,ss: Observed Predose Plasma Concentration at Steady State for Orteronel and M-I Metabolite   [ Time Frame: Cycle 1 Day 8 Predose ]

22.  Secondary:   Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)   [ Time Frame: From signing of the informed consent form through 30 days after the last dose of study drug, approximately 3.2 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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
No text entered.


  More Information

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, Clinical Science
Organization: Takeda
phone: +1-877-825-3327
e-mail: trialdisclosures@takeda.com



Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01666314     History of Changes
Other Study ID Numbers: C21013
2012-001539-30 ( EudraCT Number )
U1111-1179-5750 ( Other Identifier: WHO )
First Submitted: August 6, 2012
First Posted: August 16, 2012
Results First Submitted: January 21, 2018
Results First Posted: March 20, 2018
Last Update Posted: March 20, 2018