Clincosm LogoSign in Get a demo

Study of TAK-700 in Combination With Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer

Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01084655
Collaborator
(none)
38
Enrollment
1
Location
3
Arms
68
Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, multicenter, Phase 1/2 study of TAK-700 in combination with docetaxel and prednisone that will evaluate the safety and pharmacokinetics (PK) of the combination and will allow estimation of prostate-specific antigen (PSA) response in men with metastatic castration-resistant prostate cancer (mCRPC).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
38 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Phase 1/2 Study of TAK-700 in Combination With Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer
Study Start Date :
Jul 1, 2010
Actual Primary Completion Date :
Jan 1, 2013
Actual Study Completion Date :
Mar 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone

Orteronel (TAK-700) 200 milligram (mg), tablets, orally, twice daily (BID) starting from Day 1 along with docetaxel 75 milligram per square meter (mg/m^2), infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods.

Drug: TAK-700
TAK-700 with docetaxel and prednisone on a continuous schedule.

Drug: Docetaxel
TAK-700 with docetaxel and prednisone on a continuous schedule.

Drug: Prednisone
TAK-700 with docetaxel and prednisone on a continuous schedule.
Experimental: Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone

Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods.

Drug: TAK-700
TAK-700 with docetaxel and prednisone on a continuous schedule.

Drug: Docetaxel
TAK-700 with docetaxel and prednisone on a continuous schedule.

Drug: Prednisone
TAK-700 with docetaxel and prednisone on a continuous schedule.
Experimental: Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone

Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).

Drug: TAK-700
TAK-700 with docetaxel and prednisone on a continuous schedule.

Drug: Docetaxel
TAK-700 with docetaxel and prednisone on a continuous schedule.

Drug: Prednisone
TAK-700 with docetaxel and prednisone on a continuous schedule.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) or Serious Adverse Events (SAE) [Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)]

  2. Number of Participants With TEAEs Related to Hematology and Serum Chemistry [Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)]

  3. Number of Participants With TEAEs Related to Vital Signs [Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)]

  4. Number of Participants With TEAEs Related to Electrocardiogram (ECG) [Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)]

  5. Phase 2: Cmax: Maximum Observed Plasma Concentration for Docetaxel [Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion]

  6. Phase 2: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel [Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion]

  7. Phase 2: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Docetaxel [Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion]

  8. Phase 2: Terminal Phase Elimination Half-life (T1/2) for Docetaxel [Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion]

  9. Phase 2: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for Orteronel [Cycle 1 Day 21: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel]

  10. Phase 2: AUC 0-tau: Area Under the Plasma Concentration Versus Time Curve Zero to the Time of the End of the Dosing Interval for Orteronel [Cycle 1 Day 21: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel]

  11. Phase 2: Percentage of Participants With Prostate-specific Antigen (PSA) Response of 30 Percent (%), 50%, and 90% [Cycle 4 Day 21]

    PSA response rates (PSA-30, PSA-50, and PSA-90) were defined as greater than or equal to (>=) 30%, 50%, and 90% reductions, respectively, from baseline in PSA concentration.

  12. Phase 2: Best PSA Response [Cycle 2 Day 1 up to Cycle 12 Day 21]

    Best PSA response was defined as the maximum PSA percent reduction from baseline at any time beyond Cycle 1.

Secondary Outcome Measures

  1. Phase 2: Time to PSA Progression [Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)]

    Time to PSA progression was defined as (date of PSA progression) - (date of first dose of drug) + 1, where PSA progression was defined as: For participants whose PSA concentrations never declined before the end of Cycle 4 of treatment: a) >=25% increase over the baseline level and an increase in absolute PSA concentration >=2 ng/mL; For participants who initially experienced a PSA decline: a) >=25% increase in PSA above the nadir concentration and an increase in absolute PSA concentration >=2 ng/mL.

  2. Phase 2: Time to Radiographic Disease Progression [Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)]

    Time to Radiographic Disease Progression was defined as (date of Radiographic Disease progression) - (date of first dose of drug) + 1. Radiographic disease progression is defined as the presence of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) criteria and/or bone scan progression determined according to second Prostate Cancer Clinical Trials Working Group (PCWG2) bone scan criteria.

  3. Phase 2: Percentage of Participants With Objective Measurable Disease Response [Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)]

    Percentage of participants with objective measurable disease response based assessment of complete response (CR), partial response (PR), stable disease or PD according to RECIST (Version 1.1). A CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to less than (<)10 millimeter (mm). A PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of longest diameters of non-lymph node lesions and of the short diameter(s) or short axis of lymph nodes.

  4. Phase 2: Change From Baseline in Circulating Tumor Cells (CTCs) [Cycle 2 Day 1, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, Cycle 21 Day 1, End of treatment (approximately up to Cycle 48), Last assessment (30 days after last dose of study drug, approximately up to 1038 days)]

    Baseline is defined as the last scheduled observed measurement prior to the first dose of drug.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Each patient must meet all of the following inclusion criteria:

  • Voluntary written consent

  • Male patients 18 years or older

  • Estimated life expectancy of 6 months or more

  • Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma

  • Radiograph-documented metastatic disease

  • Progressive disease

  • Prior surgical castration or concurrent use of an agent for medical castration

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2

  • Physical examination findings that are consistent with other study entry or exclusion criteria and identified but not excluded chronic conditions

  • Even if surgically sterilized, patients must Practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug, OR Abstain from heterosexual intercourse

  • Any use of opiates must be stable for at least 2 weeks prior to study entry

  • Meet screening laboratory values as specified in protocol

  • Suitable venous access

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Known hypersensitivity to TAK-700, docetaxel, prednisone or related compounds

  • Received any of the following within 30 days prior to the first dose of TAK-700: prior therapy with any investigational compound; prior herbal product known to decrease PSA; OR radiation therapy for prostate cancer

  • Received prior therapy with TAK-700, aminoglutethimide, ketoconazole or abiraterone (for Phase 1 only, patients previously treated with ketoconazole or abiraterone will be eligible if treatment with ketoconazole or abiraterone was discontinued at least 30 days prior to enrollment)

  • Received antiandrogen therapy within 4 weeks for flutamide and 6 weeks for all others prior to first dose of study drug

  • Received prior chemotherapy for prostate cancer

  • Current spinal cord compression, bilateral hydronephrosis or neck outlet obstruction

  • Symptoms that investigator deems related to prostate cancer

  • Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected

  • Uncontrolled cardiovascular condition

  • New York Heart Association Class (NYHA) Class III or IV

  • Uncontrolled hypertension despite medical therapy

  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C

  • Unwilling or unable to comply with protocol

  • Major surgery or serious infection within 14 days of first dose of TAK-700

  • Life-threatening illness unrelated to cancer

  • Uncontrolled nausea, vomiting or diarrhea

  • Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of TAK-700

Contacts and Locations

Locations

Site City State Country Postal Code
1 Alaska Clinical Research Center, LLC Anchorage Alaska United States 99508

Sponsors and Collaborators

  • Millennium Pharmaceuticals, Inc.

Investigators

  • Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01084655
Other Study ID Numbers:
  • C21003
First Posted:
Mar 10, 2010
Last Update Posted:
Jul 30, 2019
Last Verified:
Jul 1, 2019
Additional relevant MeSH terms:
Prostatic Neoplasms
Prednisone
Docetaxel

Study Results

Participant Flow

Recruitment Details Participants took part in the study at 10 investigative sites in the United States from 22 July 2010 to 03 March 2016.
Pre-assignment Detail Male participants with a historical diagnosis of metastatic-castration resistant prostate cancer (mCRPC) were enrolled in this 2 part study to receive orteronel (TAK-700) along with docetaxel 75 milligram per square meter (mg/m^2) and prednisone 5 milligram (mg) twice daily (BID).
Arm/Group Title Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 200 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Period Title: Overall Study
STARTED 6 8 24
Treated 6 8 23
COMPLETED 0 2 5
NOT COMPLETED 6 6 19

Baseline Characteristics

Arm/Group Title Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone Total
Arm/Group Description Orteronel (TAK-700) 200 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT). Total of all reporting groups
Overall Participants 6 8 23 37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
69.7
(9.20)
65.3
(7.76)
66.2
(9.21)
66.6
(8.80)
Sex: Female, Male (Count of Participants)
Female
0
0%
0
0%
0
0%
0
0%
Male
6
100%
8
100%
23
100%
37
100%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino
6
100%
7
87.5%
22
95.7%
35
94.6%
Unknown or Not Reported
0
0%
1
12.5%
1
4.3%
2
5.4%
Race/Ethnicity, Customized (Count of Participants)
White
5
83.3%
6
75%
21
91.3%
32
86.5%
Black or African American
1
16.7%
2
25%
2
8.7%
5
13.5%
Region of Enrollment (Count of Participants)
United States
6
100%
8
100%
23
100%
37
100%
Height (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]
172.47
(8.150)
179.39
(5.452)
179.57
(6.684)
178.38
(7.018)
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]
89.08
(30.972)
98.61
(20.296)
101.83
(17.527)
99.07
(20.557)
Body mass index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]
29.525
(7.5049)
30.589
(5.9713)
31.599
(5.2488)
31.044
(5.6762)

Outcome Measures

1. Primary Outcome
Title Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) or Serious Adverse Events (SAE)
Description
Time Frame Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all participants who were enrolled and received at least 1 dose of orteronel.
Arm/Group Title Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 200 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 6 8 23
TEAE
6
100%
8
100%
23
100%
SAE
5
83.3%
5
62.5%
16
69.6%
2. Primary Outcome
Title Number of Participants With TEAEs Related to Hematology and Serum Chemistry
Description
Time Frame Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all participants who were enrolled and received at least 1 dose of orteronel.
Arm/Group Title Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 200 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 6 8 23
Neutropenia
3
50%
4
50%
8
34.8%
Anaemia
2
33.3%
0
0%
6
26.1%
Leukopenia
0
0%
1
12.5%
4
17.4%
Leukocytosis
0
0%
0
0%
3
13%
Neutrophil count decreased
1
16.7%
2
25%
4
17.4%
Blood bilirubin increased
0
0%
1
12.5%
1
4.3%
Blood creatinine increased
1
16.7%
0
0%
2
8.7%
White blood cell count decreased
0
0%
3
37.5%
6
26.1%
Gamma-glutamyltransferase increased
0
0%
0
0%
4
17.4%
Blood alkaline phosphatase increased
0
0%
0
0%
3
13%
Alanine aminotransferase increased
0
0%
0
0%
2
8.7%
Aspartate aminotransferase increased
0
0%
0
0%
2
8.7%
Hyperglycaemia
3
50%
4
50%
4
17.4%
Hypomagnesaemia
1
16.7%
2
25%
3
13%
Hyponatraemia
1
16.7%
1
12.5%
2
8.7%
Hypophosphataemia
0
0%
3
37.5%
2
8.7%
Hyperkalaemia
0
0%
3
37.5%
0
0%
3. Primary Outcome
Title Number of Participants With TEAEs Related to Vital Signs
Description
Time Frame Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all participants who were enrolled and received at least 1 dose of orteronel.
Arm/Group Title Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 200 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 6 8 23
Hypertension
3
50%
2
25%
1
4.3%
Hypotension
1
16.7%
0
0%
1
4.3%
Accelerated hypertension
0
0%
0
0%
1
4.3%
4. Primary Outcome
Title Number of Participants With TEAEs Related to Electrocardiogram (ECG)
Description
Time Frame Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all participants who were enrolled and received at least 1 dose of orteronel.
Arm/Group Title Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 200 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 6 8 23
Overall
1
16.7%
0
0%
1
4.3%
Angina pectoris
1
16.7%
0
0%
1
4.3%
5. Primary Outcome
Title Phase 2: Cmax: Maximum Observed Plasma Concentration for Docetaxel
Description
Time Frame Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion

Outcome Measure Data

Analysis Population Description
The pharmacokinetic (PK)-evaluable population included participants who had sufficient dosing data and plasma concentration-time data to permit calculation of at least 1 PK parameter.
Arm/Group Title Phase 2 Cycle 1: Docetaxel 75 mg/m^2 + Prednisone 5 mg Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 1. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 2.
Measure Participants 9 7
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]
1330
(41.6)
1600
(25.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone, Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone
Comments ANOVA with dose level as a fixed effect and participant as a random effect.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric Least Square(LS)Means
Estimated Value 1.204
Confidence Interval (2-Sided) 90%
0.870 to 1.666
Parameter Dispersion Type:
Value:
Estimation Comments
6. Primary Outcome
Title Phase 2: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel
Description
Time Frame Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion

Outcome Measure Data

Analysis Population Description
The PK-evaluable population included participants who had sufficient dosing data and plasma concentration-time data to permit calculation of at least 1 PK parameter.
Arm/Group Title Phase 2 Cycle 1: Docetaxel 75 mg/m^2 + Prednisone 5 mg Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 1. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 2.
Measure Participants 9 7
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)]
1180
(43.7)
1270
(25.0)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone, Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone
Comments ANOVA with dose level as a fixed effect and participant as a random effect.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Means
Estimated Value 1.074
Confidence Interval (2-Sided) 90%
0.793 to 1.455
Parameter Dispersion Type:
Value:
Estimation Comments
7. Primary Outcome
Title Phase 2: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Docetaxel
Description
Time Frame Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion

Outcome Measure Data

Analysis Population Description
Data was not calculated since no participant was available for analysis.
Arm/Group Title Phase 2 Cycle 1: Docetaxel 75 mg/m^2 + Prednisone 5 mg Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 1. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 2.
Measure Participants 0 0
8. Primary Outcome
Title Phase 2: Terminal Phase Elimination Half-life (T1/2) for Docetaxel
Description
Time Frame Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion

Outcome Measure Data

Analysis Population Description
Data was not calculated since no participant was available for analysis.
Arm/Group Title Phase 2 Cycle 1: Docetaxel 75 mg/m^2 + Prednisone 5 mg Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 1. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 2.
Measure Participants 0 0
9. Primary Outcome
Title Phase 2: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for Orteronel
Description
Time Frame Cycle 1 Day 21: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel

Outcome Measure Data

Analysis Population Description
PK set where Cmax,ss data was available. The PK-evaluable population included participants who had sufficient dosing data and plasma concentration-time data to permit calculation of at least 1 PK parameter.
Arm/Group Title Phase 2 Cycle 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel 400 mg, tablets, orally, BID, on Day 21 of Treatment Cycle 1 along with docetaxel 75 mg/m^2, injection, intravenously on Day 1 and prednisone 5 mg, tablets, orally, BID from Day 1 up to Day 21 of Treatment Cycle 1. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 2.
Measure Participants 7 5
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
2660
(38.8)
3000
(27.1)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone, Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone
Comments ANOVA with dose level as a fixed effect and participant as a random effect.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Means
Estimated Value 1.066
Confidence Interval (2-Sided) 90%
0.802 to 1.417
Parameter Dispersion Type:
Value:
Estimation Comments
10. Primary Outcome
Title Phase 2: AUC 0-tau: Area Under the Plasma Concentration Versus Time Curve Zero to the Time of the End of the Dosing Interval for Orteronel
Description
Time Frame Cycle 1 Day 21: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel

Outcome Measure Data

Analysis Population Description
The PK-evaluable population included participants who had sufficient dosing data and plasma concentration-time data to permit calculation of at least 1 PK parameter.
Arm/Group Title Phase 2 Cycle 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel 400 mg, tablets, orally, BID, on Day 21 of Treatment Cycle 1 along with docetaxel 75 mg/m^2, injection, intravenously on Day 1 and prednisone 5 mg, tablets, orally, BID from Day 1 up to Day 21 of Treatment Cycle 1. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of Treatment Cycle 2.
Measure Participants 9 7
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
18000
(14.6)
871
(44.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone, Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone
Comments ANOVA with dose level as a fixed effect and participant as a random effect.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Means
Estimated Value 1.068
Confidence Interval (2-Sided) 90%
0.955 to 1.195
Parameter Dispersion Type:
Value:
Estimation Comments
11. Primary Outcome
Title Phase 2: Percentage of Participants With Prostate-specific Antigen (PSA) Response of 30 Percent (%), 50%, and 90%
Description PSA response rates (PSA-30, PSA-50, and PSA-90) were defined as greater than or equal to (>=) 30%, 50%, and 90% reductions, respectively, from baseline in PSA concentration.
Time Frame Cycle 4 Day 21

Outcome Measure Data

Analysis Population Description
The PSA-evaluable population included all participants with a baseline PSA evaluation and at least 1 PSA evaluation beyond Cycle 1, or participants with baseline PSA evaluation without a beyond-cycle-1 PSA evaluation due to PSA progression, disease progression, unacceptable adverse event (AE), or death.
Arm/Group Title Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 22
PSA-30
68
1133.3%
PSA-50
59
983.3%
PSA-90
23
383.3%
12. Primary Outcome
Title Phase 2: Best PSA Response
Description Best PSA response was defined as the maximum PSA percent reduction from baseline at any time beyond Cycle 1.
Time Frame Cycle 2 Day 1 up to Cycle 12 Day 21

Outcome Measure Data

Analysis Population Description
The PSA-evaluable population included all participants with a baseline PSA evaluation and at least 1 PSA evaluation beyond Cycle 1, or participants with baseline PSA evaluation without a beyond-cycle-1 PSA evaluation due to PSA progression, disease progression, unacceptable AE, or death.
Arm/Group Title Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 22
Mean (Standard Deviation) [percent change]
-61.72
(51.609)
13. Secondary Outcome
Title Phase 2: Time to PSA Progression
Description Time to PSA progression was defined as (date of PSA progression) - (date of first dose of drug) + 1, where PSA progression was defined as: For participants whose PSA concentrations never declined before the end of Cycle 4 of treatment: a) >=25% increase over the baseline level and an increase in absolute PSA concentration >=2 ng/mL; For participants who initially experienced a PSA decline: a) >=25% increase in PSA above the nadir concentration and an increase in absolute PSA concentration >=2 ng/mL.
Time Frame Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all participants who were enrolled and received at least 1 dose of orteronel.
Arm/Group Title Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 23
Median (95% Confidence Interval) [days]
203
(51.609)
14. Secondary Outcome
Title Phase 2: Time to Radiographic Disease Progression
Description Time to Radiographic Disease Progression was defined as (date of Radiographic Disease progression) - (date of first dose of drug) + 1. Radiographic disease progression is defined as the presence of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) criteria and/or bone scan progression determined according to second Prostate Cancer Clinical Trials Working Group (PCWG2) bone scan criteria.
Time Frame Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all participants who were enrolled and received at least 1 dose of orteronel.
Arm/Group Title Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 23
Median (95% Confidence Interval) [days]
393
(51.609)
15. Secondary Outcome
Title Phase 2: Percentage of Participants With Objective Measurable Disease Response
Description Percentage of participants with objective measurable disease response based assessment of complete response (CR), partial response (PR), stable disease or PD according to RECIST (Version 1.1). A CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to less than (<)10 millimeter (mm). A PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of longest diameters of non-lymph node lesions and of the short diameter(s) or short axis of lymph nodes.
Time Frame Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)

Outcome Measure Data

Analysis Population Description
The RECIST-evaluable population was defined as all participants with measurable disease by RECIST (Version 1.1) at baseline, and with at least 1 postbaseline tumor response assessment (RECIST, Version 1.1).
Arm/Group Title Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 10
Complete response
0
(51.609) 0%
Partial response
70
1166.7%
Stable Disease
30
500%
Progressive Disease
0
0%
16. Secondary Outcome
Title Phase 2: Change From Baseline in Circulating Tumor Cells (CTCs)
Description Baseline is defined as the last scheduled observed measurement prior to the first dose of drug.
Time Frame Cycle 2 Day 1, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, Cycle 21 Day 1, End of treatment (approximately up to Cycle 48), Last assessment (30 days after last dose of study drug, approximately up to 1038 days)

Outcome Measure Data

Analysis Population Description
Safety analysis set where baseline and post-baseline assessments were available. The safety analysis set included all participants who were enrolled and received at least 1 dose of orteronel.
Arm/Group Title Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
Measure Participants 21
Baseline (n=21)
47.9
(108.85)
Change at Cycle 2 Day 1 (n=12)
-11.9
(24.57)
Change at Cycle 5 Day 1 (n=16)
-39.0
(80.35)
Change at Cycle 9 Day 1 (n=6)
-25.5
(35.07)
Change at Cycle 13 Day 1 (n=7)
-11.3
(27.72)
Change at Cycle 17 Day 1 (n=5)
-18.8
(31.93)
Change at Cycle 21 Day 1 (n=1)
-5.0
(NA)
Change at End of treatment (n=11)
-40.2
(66.43)
Change at Last assessment (n=18)
-35.0
(76.30)

Adverse Events

Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to Part 1: Cycle 29 Day 21; Part 2: Cycle 12 Day 21).
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Arm/Group Description Orteronel (TAK-700) 200 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods. Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15, then given continuously along with docetaxel 75 mg/m^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).
All Cause Mortality
Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 5/6 (83.3%) 5/8 (62.5%) 16/23 (69.6%)
Blood and lymphatic system disorders
Febrile neutropenia 1/6 (16.7%) 1/8 (12.5%) 3/23 (13%)
Neutropenia 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Anaemia 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Cardiac disorders
Atrial fibrillation 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Pericardial effusion 0/6 (0%) 1/8 (12.5%) 0/23 (0%)
Cardio-respiratory arrest 1/6 (16.7%) 0/8 (0%) 0/23 (0%)
Gastrointestinal disorders
Pancreatitis 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Duodenal ulcer haemorrhage 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Abdominal distension 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Vomiting 0/6 (0%) 1/8 (12.5%) 0/23 (0%)
General disorders
Asthenia 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Fatigue 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Pyrexia 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Hepatobiliary disorders
Hepatitis cholestatic 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Immune system disorders
Drug hypersensitivity 1/6 (16.7%) 0/8 (0%) 0/23 (0%)
Infections and infestations
Cellulitis 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Pneumonia bacterial 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Urinary tract infection 1/6 (16.7%) 0/8 (0%) 2/23 (8.7%)
Pneumonia 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Sepsis 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Urosepsis 1/6 (16.7%) 0/8 (0%) 0/23 (0%)
Pseudomonal sepsis 1/6 (16.7%) 0/8 (0%) 0/23 (0%)
Gastroenteritis viral 1/6 (16.7%) 0/8 (0%) 0/23 (0%)
Skin infection 0/6 (0%) 1/8 (12.5%) 0/23 (0%)
Investigations
Amylase increased 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Lipase increased 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
International normalised ratio increased 1/6 (16.7%) 0/8 (0%) 0/23 (0%)
Metabolism and nutrition disorders
Dehydration 0/6 (0%) 2/8 (25%) 3/23 (13%)
Hyperkalaemia 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Vitamin B12 deficiency 1/6 (16.7%) 0/8 (0%) 0/23 (0%)
Hypomagnesaemia 0/6 (0%) 1/8 (12.5%) 0/23 (0%)
Musculoskeletal and connective tissue disorders
Bone pain 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Arthralgia 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Metastases to bone 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Prostate cancer metastatic 1/6 (16.7%) 0/8 (0%) 0/23 (0%)
Psychiatric disorders
Confusional state 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Renal and urinary disorders
Bladder perforation 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Urinary bladder haemorrhage 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Renal failure 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Acute kidney injury 0/6 (0%) 1/8 (12.5%) 0/23 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis 0/6 (0%) 1/8 (12.5%) 2/23 (8.7%)
Dyspnoea exertional 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Respiratory distress 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Hypoxia 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Pulmonary embolism 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Vascular disorders
Deep vein thrombosis 0/6 (0%) 0/8 (0%) 1/23 (4.3%)
Other (Not Including Serious) Adverse Events
Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/6 (100%) 8/8 (100%) 23/23 (100%)
Blood and lymphatic system disorders
Neutropenia 3/6 (50%) 4/8 (50%) 8/23 (34.8%)
Anaemia 2/6 (33.3%) 0/8 (0%) 5/23 (21.7%)
Leukopenia 0/6 (0%) 1/8 (12.5%) 4/23 (17.4%)
Leukocytosis 0/6 (0%) 0/8 (0%) 3/23 (13%)
Cardiac disorders
Angina pectoris 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Eye disorders
Lacrimation increased 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Gastrointestinal disorders
Diarrhoea 4/6 (66.7%) 3/8 (37.5%) 11/23 (47.8%)
Nausea 3/6 (50%) 5/8 (62.5%) 10/23 (43.5%)
Constipation 3/6 (50%) 2/8 (25%) 9/23 (39.1%)
Abdominal pain 0/6 (0%) 1/8 (12.5%) 4/23 (17.4%)
Dry mouth 1/6 (16.7%) 1/8 (12.5%) 2/23 (8.7%)
Dyspepsia 1/6 (16.7%) 2/8 (25%) 1/23 (4.3%)
Stomatitis 1/6 (16.7%) 0/8 (0%) 3/23 (13%)
Abdominal pain upper 0/6 (0%) 2/8 (25%) 1/23 (4.3%)
Vomiting 0/6 (0%) 0/8 (0%) 3/23 (13%)
Abdominal discomfort 0/6 (0%) 2/8 (25%) 0/23 (0%)
Flatulence 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Haemorrhoids 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
General disorders
Fatigue 5/6 (83.3%) 8/8 (100%) 17/23 (73.9%)
Pyrexia 1/6 (16.7%) 2/8 (25%) 4/23 (17.4%)
Asthenia 0/6 (0%) 2/8 (25%) 3/23 (13%)
Oedema peripheral 1/6 (16.7%) 1/8 (12.5%) 2/23 (8.7%)
Chills 1/6 (16.7%) 1/8 (12.5%) 1/23 (4.3%)
Pain 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Peripheral swelling 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Immune system disorders
Drug hypersensitivity 1/6 (16.7%) 1/8 (12.5%) 0/23 (0%)
Infections and infestations
Upper respiratory tract infection 2/6 (33.3%) 1/8 (12.5%) 3/23 (13%)
Bronchitis 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Conjunctivitis 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Fungal skin infection 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Nasopharyngitis 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Oral candidiasis 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Sinusitis 2/6 (33.3%) 0/8 (0%) 0/23 (0%)
Urinary tract infection 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Injury, poisoning and procedural complications
Fall 0/6 (0%) 1/8 (12.5%) 4/23 (17.4%)
Contusion 1/6 (16.7%) 0/8 (0%) 2/23 (8.7%)
Post-traumatic pain 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Skin abrasion 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Investigations
Weight decreased 2/6 (33.3%) 3/8 (37.5%) 4/23 (17.4%)
White blood cell count decreased 0/6 (0%) 3/8 (37.5%) 6/23 (26.1%)
Neutrophil count decreased 1/6 (16.7%) 2/8 (25%) 4/23 (17.4%)
Gamma-glutamyltransferase increased 0/6 (0%) 0/8 (0%) 4/23 (17.4%)
Blood alkaline phosphatase increased 0/6 (0%) 0/8 (0%) 3/23 (13%)
Blood creatinine increased 1/6 (16.7%) 0/8 (0%) 2/23 (8.7%)
Alanine aminotransferase increased 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Aspartate aminotransferase increased 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Blood bilirubin increased 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Blood phosphorus decreased 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Ejection fraction decreased 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Weight increased 2/6 (33.3%) 0/8 (0%) 0/23 (0%)
Metabolism and nutrition disorders
Decreased appetite 3/6 (50%) 3/8 (37.5%) 8/23 (34.8%)
Hyperglycaemia 3/6 (50%) 4/8 (50%) 4/23 (17.4%)
Dehydration 3/6 (50%) 2/8 (25%) 5/23 (21.7%)
Hypomagnesaemia 1/6 (16.7%) 2/8 (25%) 3/23 (13%)
Hyponatraemia 1/6 (16.7%) 1/8 (12.5%) 2/23 (8.7%)
Hyperkalaemia 0/6 (0%) 3/8 (37.5%) 0/23 (0%)
Hypophosphataemia 0/6 (0%) 3/8 (37.5%) 0/23 (0%)
Diabetes mellitus 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Hypocalcaemia 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Musculoskeletal and connective tissue disorders
Muscle spasms 1/6 (16.7%) 3/8 (37.5%) 5/23 (21.7%)
Arthralgia 2/6 (33.3%) 0/8 (0%) 6/23 (26.1%)
Back pain 1/6 (16.7%) 1/8 (12.5%) 6/23 (26.1%)
Myalgia 0/6 (0%) 3/8 (37.5%) 5/23 (21.7%)
Bone pain 0/6 (0%) 1/8 (12.5%) 4/23 (17.4%)
Muscular weakness 1/6 (16.7%) 1/8 (12.5%) 3/23 (13%)
Pain in extremity 0/6 (0%) 0/8 (0%) 5/23 (21.7%)
Musculoskeletal chest pain 0/6 (0%) 1/8 (12.5%) 3/23 (13%)
Flank pain 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Nervous system disorders
Dysgeusia 0/6 (0%) 4/8 (50%) 9/23 (39.1%)
Peripheral sensory neuropathy 0/6 (0%) 3/8 (37.5%) 5/23 (21.7%)
Neuropathy peripheral 0/6 (0%) 0/8 (0%) 5/23 (21.7%)
Dizziness 1/6 (16.7%) 1/8 (12.5%) 2/23 (8.7%)
Headache 1/6 (16.7%) 1/8 (12.5%) 2/23 (8.7%)
Hypoaesthesia 1/6 (16.7%) 2/8 (25%) 0/23 (0%)
Paraesthesia 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Restless legs syndrome 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Tremor 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Psychiatric disorders
Insomnia 3/6 (50%) 2/8 (25%) 5/23 (21.7%)
Anxiety 2/6 (33.3%) 1/8 (12.5%) 1/23 (4.3%)
Depression 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Renal and urinary disorders
Pollakiuria 0/6 (0%) 0/8 (0%) 5/23 (21.7%)
Dysuria 0/6 (0%) 0/8 (0%) 4/23 (17.4%)
Haematuria 0/6 (0%) 2/8 (25%) 2/23 (8.7%)
Nocturia 1/6 (16.7%) 2/8 (25%) 1/23 (4.3%)
Micturition urgency 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Urinary incontinence 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Respiratory, thoracic and mediastinal disorders
Cough 1/6 (16.7%) 2/8 (25%) 8/23 (34.8%)
Dyspnoea 2/6 (33.3%) 2/8 (25%) 4/23 (17.4%)
Dyspnoea exertional 0/6 (0%) 2/8 (25%) 1/23 (4.3%)
Epistaxis 0/6 (0%) 1/8 (12.5%) 1/23 (4.3%)
Pleural effusion 1/6 (16.7%) 1/8 (12.5%) 0/23 (0%)
Skin and subcutaneous tissue disorders
Alopecia 2/6 (33.3%) 6/8 (75%) 14/23 (60.9%)
Ecchymosis 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Erythema 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Hyperhidrosis 1/6 (16.7%) 1/8 (12.5%) 0/23 (0%)
Nail discolouration 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Onychomadesis 0/6 (0%) 0/8 (0%) 2/23 (8.7%)
Pruritus 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Rash macular 1/6 (16.7%) 1/8 (12.5%) 0/23 (0%)
Rash maculo-papular 1/6 (16.7%) 0/8 (0%) 1/23 (4.3%)
Vascular disorders
Hypertension 3/6 (50%) 2/8 (25%) 2/23 (8.7%)
Flushing 0/6 (0%) 2/8 (25%) 2/23 (8.7%)
Hot flush 0/6 (0%) 1/8 (12.5%) 3/23 (13%)
Hypotension 2/6 (33.3%) 1/8 (12.5%) 1/23 (4.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.

Results Point of Contact

Name/Title Medical Director
Organization Takeda
Phone +1-877-825-3327
Email trialdisclosures@takeda.com
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01084655
Other Study ID Numbers:
  • C21003
First Posted:
Mar 10, 2010
Last Update Posted:
Jul 30, 2019
Last Verified:
Jul 1, 2019