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
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01666314
Collaborator
(none)
137
1
8
48.4
2.8
Study Details
Study Description
Brief Summary
This is a double-blind, placebo-controlled, multiregional Phase1/2 study to characterize the pharmacokinetic and pharmacodynamic responses to orteronel when administered concomitantly with prednisone in Chemotherapy-Naive Participants With Castration-Resistant Prostate Cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The drug being tested in this study is called orteronel. Orteronel is being tested to treat adult males who have adenocarcinoma of the prostate. This study will look at the pharmacokinetics (how the drug moves through the body) and pharmacodynamics (how the drug effects the body) in people who take orteronel in addition to prednisone.
The study will enroll approximately 144 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the eight treatment groups (4 in Japan, 4 in Ex-Japan) which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).
In Japan:
Participants were randomized in a ratio of 2:1:2:1
-
200 mg orteronel or Placebo-matching orteronel [(dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient] twice daily (BID) + prednisone
-
300 mg orteronel, or Placebo-matching orteronel, BID + prednisone Ex-Japan Participants were randomized in a ratio of 2:1:2:1
-
200 mg orteronel or Placebo-matching orteronel, BID in Cycle 1 + prednisone
-
400 mg orteronel, or Placebo-matching orteronel ,BID in Cycle 1 + Prednisone
Participants initially randomized to placebo received 4 weeks of placebo and then 12 weeks of active treatment with orteronel then entered a follow-up period treatment period. Participants initially randomized to orteronel received 16 weeks of treatment then entered a follow-up treatment period.
This multi-centre trial will be conducted worldwide. The overall time to participate in this study is approximately 3.2 years. Participants will make multiple visits to the clinic and a final visit 30 to 40 days after receiving their last dose of study drug for a follow-up assessment.
Study Design
Study Type:
Interventional
Actual Enrollment
:
137 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Study in Japan and Ex-Japan to Characterize the Pharmacokinetic and Pharmacodynamic Response to Orteronel (TAK-700) in Chemotherapy-Naive Patients With Castration-Resistant Prostate Cancer
Actual Study Start Date
:
Aug 20, 2012
Actual Primary Completion Date
:
Sep 12, 2013
Actual Study Completion Date
:
Sep 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Placebo + Orteronel 200 mg (Japan) Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days) followed by orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in 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. |
Drug: Orteronel
Orteronel tablets
Drug: Orteronel Placebo
Orteronel placebo-matching tablets
Drug: Prednisone
Prednisone 5 mg
|
| Experimental: 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. |
Drug: Orteronel
Orteronel tablets
Drug: Prednisone
Prednisone 5 mg
|
| Other: 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. |
Drug: Orteronel
Orteronel tablets
Drug: Orteronel Placebo
Orteronel placebo-matching tablets
Drug: Prednisone
Prednisone 5 mg
|
| Experimental: 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. |
Drug: Orteronel
Orteronel tablets
Drug: Prednisone
Prednisone 5 mg
|
| Other: 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. |
Drug: Orteronel
Orteronel tablets
|
| Experimental: 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. |
Drug: Orteronel
Orteronel tablets
Drug: Prednisone
Prednisone 5 mg
|
| Other: 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. |
Drug: Orteronel
Orteronel tablets
Drug: Orteronel Placebo
Orteronel placebo-matching tablets
Drug: Prednisone
Prednisone 5 mg
|
| Experimental: 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. |
Drug: Orteronel
Orteronel tablets
Drug: Prednisone
Prednisone 5 mg
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Serum Testosterone Levels Reduced to ≤ 2 ng/dL After 4 Weeks of Treatment in Japan [Baseline and Week 4]
Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory.
Secondary Outcome Measures
- Percentage of Participants With Serum Testosterone Levels Reduced to ≤ 2 ng/dL in Ex-Japan [Baseline and Week 4]
Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory.
- Percent Change From Baseline in Serum Testosterone Level After 4 Weeks of Treatment [Baseline and Week 4]
Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory.
- Percent Change From Baseline in Serum Testosterone Level After 12 Weeks of Treatment [Baseline and Week 12]
Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory.
- Percentage of Participants With Prostate-Specific Antigen Reduction ≥ 50% (PSA50) After 4 Weeks of Treatment [Baseline and Week 4]
A 50% PSA response rate (PSA50) was defined as PSA reduction ≥ 50% from Baseline.
- Percentage of Participants With PSA50 After 12 Weeks of Treatment [Baseline and Week 12]
A 50% PSA response rate (PSA50) was defined as PSA reduction ≥ 50% from Baseline.
- Absolute Values for Testosterone [Baseline, Cycle 1 Day 8 and Cycle 2 Day 1]
Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory.
- Absolute Values for Dehydroepiandrosterone Sulfate (DHEA-S) [Baseline, Cycle 1 Day 8 and Cycle 2 Day 1]
Serum Ultra low level quantification of DHEA-S was measured by liquid chromatography and mass spectrometry (LC/MS) at a central laboratory.
- Absolute Values for Adrenocorticotropic Hormone (ACTH) [Baseline, Cycle 1 Day 8 and Cycle 2 Day 1]
Serum ACTH was measured by immunometric assay at the central laboratory.
- Absolute Values for Corticosterone [Baseline, Cycle 1 Day 8 and Cycle 2 Day 1]
Serum Corticosterone was measured by high pressure liquid chromatography with mass spectrometry at the central laboratory.
- Absolute Values for Cortisol [Baseline, Cycle 1 Day 8 and Cycle 2 Day 1]
Serum Cortisol was measured by immunometric assay at the central laboratory.
- Absolute Values for Prostate-Specific Antigen (PSA) [Baseline and Cycle 2 Day 1]
Serum PSA was measured at the central laboratory.
- Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite [Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 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.
- AUC(0-12): Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours Post-dose for Orteronel and M-I Metabolite [Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose]
AUC(0-12) is measure of area under the curve over the dosing interval where the length of the dosing interval is time 0 to 12 hours in this study.
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite [Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose]
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
- AE (0-24) Cumulative Amount of Drug Excreted Into the Urine for Orteronel and MI-Metabolite [Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose]
Cumulative amount of urine excreted time 0 to 24 hour.
- Cmax,ss: Maximum Observed Plasma Concentration at Steady State for Orteronel and MI-Metabolite [Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose]
Maximum observed steady-state plasma concentration during a dosing interval.
- 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 [Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose]
Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax at steady state.
- 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 [Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose]
Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.
- Rac: Accumulation Index for Orteronel and M-I Metabolite [Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose]
Rac was calculated as the ratio of AUCtau to AUC12hr.
- Ctrough,ss: Observed Predose Plasma Concentration at Steady State for Orteronel and M-I Metabolite [Cycle 1 Day 8 Predose]
Observed predose plasma concentration at steady state.
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From signing of the informed consent form through 30 days after the last dose of study drug, approximately 3.2 years]
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 A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male participants 18 years or older
-
Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
-
Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma
-
Prior surgical castration or concurrent use of an agent for medical castration [e.g. Gonadotropin-releasing hormone (GnRH) analogue]
-
Prostate-Specific Antigen (PSA) ≥ 2 ng/mL at screening
-
Progressive disease based on PSA and/or radiographic criteria
Exclusion Criteria:
-
Prior therapy with orteronel, ketoconazole, aminoglutethimide, or abiraterone.
-
Known hypersensitivity to compounds related to orteronel, orteronel excipients, prednisone (or commercially available equivalent), or GnRH analogue.
-
All antiandrogen therapy (including bicalutamide) is excluded within 4 weeks before the first dose of study drug. Any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5- alpha reductase inhibitors (e.g., finasteride or dutasteride), must be discontinued 2 weeks before the first dose of study drug.
-
Continuous daily use of oral prednisone (or commercially available equivalent), oral dexamethasone, or other systemic corticosteroids for more than 2 weeks within the 3 months before screening (inhaled, nasal, and local steroids [e.g., joint injection] are allowed).
-
Prior chemotherapy for prostate cancer, with the exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years before screening.
Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Urology Cancer Center, PC | Omaha | Nebraska | United States | 68130 |
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:
NCT01666314
Other Study ID Numbers:
- C21013
- 2012-001539-30
- U1111-1179-5750
First Posted:
Aug 16, 2012
Last Update Posted:
Mar 20, 2018
Last Verified:
Feb 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Millennium Pharmaceuticals, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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 Detail | 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. |
| Arm/Group Title | Placebo + Orteronel 200 mg (Japan) | Placebo + Orteronel 300 mg (Japan) | Placebo + Orteronel 200 mg (Ex-Japan) | Placebo + Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 33 | 32 | 36 | 36 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 33 | 32 | 36 | 36 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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, 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. | 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, 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 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, 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 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, 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 of all reporting groups |
| Overall Participants | 11 | 22 | 10 | 22 | 11 | 25 | 12 | 24 | 137 |
| Age (years) [Mean (Full Range) ] | |||||||||
| Mean (Full Range) [years] |
72.1
|
68.5
|
70.1
|
71.5
|
69.6
|
69.9
|
73.3
|
69.4
|
70.6
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
11
100%
|
22
100%
|
10
100%
|
22
100%
|
11
100%
|
25
100%
|
12
100%
|
24
100%
|
137
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||
| Hispanic or Latino |
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%
|
22
100%
|
10
100%
|
22
100%
|
11
100%
|
25
100%
|
12
100%
|
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%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||||||
| White |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
11
100%
|
25
100%
|
11
91.7%
|
23
95.8%
|
70
51.1%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
1
4.2%
|
2
1.5%
|
| Asian - Japanese |
11
100%
|
22
100%
|
10
100%
|
22
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
65
47.4%
|
| Region of Enrollment (participants) [Number] | |||||||||
| Japan |
11
100%
|
22
100%
|
10
100%
|
22
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
65
47.4%
|
| Australia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
27.3%
|
1
4%
|
2
16.7%
|
2
8.3%
|
8
5.8%
|
| Greece |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
18.2%
|
4
16%
|
1
8.3%
|
3
12.5%
|
10
7.3%
|
| Ireland |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
18.2%
|
5
20%
|
3
25%
|
3
12.5%
|
13
9.5%
|
| Netherlands |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
6
24%
|
1
8.3%
|
5
20.8%
|
13
9.5%
|
| United Kingdom |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
1
8.3%
|
1
4.2%
|
3
2.2%
|
| United States |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
18.2%
|
9
36%
|
4
33.3%
|
10
41.7%
|
25
18.2%
|
| Height (cm) [Mean (Full Range) ] | |||||||||
| Mean (Full Range) [cm] |
161.94
|
167.10
|
163.92
|
164.71
|
170.41
|
174.79
|
176.70
|
174.74
|
169.29
|
| Weight (kg) [Mean (Full Range) ] | |||||||||
| Mean (Full Range) [kg] |
65.82
|
70.32
|
65.75
|
64.49
|
87.34
|
90.39
|
88.23
|
89.85
|
77.77
|
| Body Mass Index (BMI) (kg/m^2) [Mean (Full Range) ] | |||||||||
| Mean (Full Range) [kg/m^2] |
25.05
|
25.21
|
24.43
|
23.73
|
29.85
|
29.61
|
28.37
|
29.40
|
26.96
|
Outcome Measures
| Title | Percentage of Participants With Serum Testosterone Levels Reduced to ≤ 2 ng/dL After 4 Weeks of Treatment in Japan |
|---|---|
| Description | Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics-evaluable population was defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement. |
| Arm/Group Title | Placebo (Japan) | Orteronel 300 mg (Japan) |
|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. |
| Measure Participants | 21 | 22 |
| Number (95% Confidence Interval) [percentage of participants] |
86.0
781.8%
|
100.0
454.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Japan), Orteronel 300 mg (Japan) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1078 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants With Serum Testosterone Levels Reduced to ≤ 2 ng/dL in Ex-Japan |
|---|---|
| Description | Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics-evaluable population was defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement. |
| Arm/Group Title | Placebo (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. |
| Measure Participants | 23 | 24 |
| Number (95% Confidence Interval) [percentage of participants] |
48.0
436.4%
|
79.0
359.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Japan), Orteronel 300 mg (Japan) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0355 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 4.145 | |
| Confidence Interval |
(2-Sided) 95% 0.9895 to 18.7606 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds ratio >1 favors orteronel. | |
| Title | Percent Change From Baseline in Serum Testosterone Level After 4 Weeks of Treatment |
|---|---|
| Description | Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the Pharmacodynamics-evaluable population, defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement, with data available after 4 Weeks of Treatment. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 22 | 22 | 20 | 21 | 22 |
| Mean (Standard Deviation) [percent change] |
-87.666
(10.4250)
|
-97.245
(1.2548)
|
-96.812
(2.7055)
|
-63.702
(43.3941)
|
-86.268
(37.2015)
|
-53.954
(118.8050)
|
| Title | Percent Change From Baseline in Serum Testosterone Level After 12 Weeks of Treatment |
|---|---|
| Description | Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory. |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the Pharmacodynamics-evaluable population, defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement, with data available after 12 Weeks of Treatment. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 31 | 26 | 28 | 31 |
| Mean (Standard Deviation) [percent change] |
-95.804
(5.3367)
|
-95.703
(5.7468)
|
-91.311
(17.5217)
|
-14.442
(406.3116)
|
| Title | Percentage of Participants With Prostate-Specific Antigen Reduction ≥ 50% (PSA50) After 4 Weeks of Treatment |
|---|---|
| Description | A 50% PSA response rate (PSA50) was defined as PSA reduction ≥ 50% from Baseline. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the Pharmacodynamics-evaluable population, defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement, with data available after 4 Weeks of Treatment. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 22 | 22 | 23 | 25 | 24 |
| Number (95% Confidence Interval) [percentage of participants] |
48.0
436.4%
|
50.0
227.3%
|
41.0
410%
|
17.0
77.3%
|
48.0
436.4%
|
46.0
184%
|
| Title | Percentage of Participants With PSA50 After 12 Weeks of Treatment |
|---|---|
| Description | A 50% PSA response rate (PSA50) was defined as PSA reduction ≥ 50% from Baseline. |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the Pharmacodynamics-evaluable population, defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement, with data available after 12 Weeks of Treatment. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 33 | 32 | 36 | 36 |
| Number (95% Confidence Interval) [percentage of participants] |
55.0
500%
|
47.0
213.6%
|
56.0
560%
|
44.0
200%
|
| Title | Absolute Values for Testosterone |
|---|---|
| Description | Serum Ultra-sensitive testosterone was measured by liquid chromatography at a central laboratory. |
| Time Frame | Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics-evaluable population was defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 22 | 22 | 23 | 25 | 24 |
| Baseline |
9.749
(3.8460)
|
9.079
(4.4581)
|
10.148
(4.6504)
|
9.173
(5.6123)
|
9.263
(5.6572)
|
14.588
(13.9833)
|
| Cycle 1 Day 8 |
1.957
(2.2843)
|
0.213
(0.0449)
|
0.251
(0.1727)
|
3.509
(4.3471)
|
0.345
(0.2770)
|
6.658
(20.4347)
|
| Cycle 2 Day 1 |
1.096
(0.7751)
|
0.203
(0.0145)
|
0.270
(0.2311)
|
3.095
(3.7254)
|
0.266
(0.1837)
|
11.720
(45.1753)
|
| Title | Absolute Values for Dehydroepiandrosterone Sulfate (DHEA-S) |
|---|---|
| Description | Serum Ultra low level quantification of DHEA-S was measured by liquid chromatography and mass spectrometry (LC/MS) at a central laboratory. |
| Time Frame | Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics-evaluable population was defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 22 | 22 | 23 | 25 | 24 |
| Baseline |
1928.0
(1306.59)
|
2529.0
(1309.39)
|
2340.9
(1606.36)
|
2601.7
(3009.41)
|
1783.0
(1554.76)
|
2155.7
(1591.51)
|
| Cycle 1 Day 8 |
414.9
(392.63)
|
63.4
(55.11)
|
71.8
(80.23)
|
973.8
(1677.95)
|
116.9
(161.01)
|
226.6
(328.70)
|
| Cycle 2 Day 1 |
268.9
(357.32)
|
14.5
(21.83)
|
36.3
(123.48)
|
815.7
(1918.88)
|
21.5
(25.68)
|
180.6
(527.03)
|
| Title | Absolute Values for Adrenocorticotropic Hormone (ACTH) |
|---|---|
| Description | Serum ACTH was measured by immunometric assay at the central laboratory. |
| Time Frame | Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics-evaluable population was defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 22 | 22 | 23 | 25 | 24 |
| Baseline |
5.0
(1.66)
|
5.5
(2.54)
|
8.3
(4.98)
|
4.7
(2.06)
|
6.0
(4.05)
|
6.4
(4.04)
|
| Cycle 1 Day 8 |
3.1
(2.68)
|
2.3
(1.55)
|
3.0
(2.70)
|
3.1
(2.62)
|
3.8
(3.04)
|
3.2
(2.56)
|
| Cycle 2 Day 1 |
1.7
(1.19)
|
1.7
(1.08)
|
2.7
(2.17)
|
3.0
(1.73)
|
3.7
(4.38)
|
3.6
(2.26)
|
| Title | Absolute Values for Corticosterone |
|---|---|
| Description | Serum Corticosterone was measured by high pressure liquid chromatography with mass spectrometry at the central laboratory. |
| Time Frame | Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics-evaluable population was defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 22 | 22 | 23 | 25 | 24 |
| Baseline |
5.946
(3.4433)
|
6.515
(4.8246)
|
7.768
(6.8625)
|
6.317
(4.1467)
|
10.030
(7.7341)
|
17.975
(35.0695)
|
| Cycle 1 Day 8 |
1.530
(1.6404)
|
11.067
(14.4220)
|
9.709
(13.4538)
|
5.598
(7.1366)
|
48.668
(66.3904)
|
60.301
(77.5434)
|
| Cycle 2 Day 1 |
0.758
(0.5108)
|
11.108
(9.0708)
|
14.654
(9.2064)
|
4.321
(6.4063)
|
29.929
(35.5565)
|
47.204
(53.4566)
|
| Title | Absolute Values for Cortisol |
|---|---|
| Description | Serum Cortisol was measured by immunometric assay at the central laboratory. |
| Time Frame | Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics-evaluable population was defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 22 | 22 | 23 | 25 | 24 |
| Baseline |
366.5
(116.69)
|
371.3
(119.38)
|
383.4
(125.98)
|
384.8
(117.14)
|
449.0
(131.54)
|
446.8
(193.09)
|
| Cycle 1 Day 8 |
82.3
(46.16)
|
49.5
(25.53)
|
55.5
(55.97)
|
175.8
(107.82)
|
100.9
(87.38)
|
122.0
(88.70)
|
| Cycle 2 Day 1 |
53.9
(24.92)
|
49.2
(21.71)
|
54.3
(39.93)
|
149.6
(122.91)
|
97.2
(85.66)
|
109.1
(83.19)
|
| Title | Absolute Values for Prostate-Specific Antigen (PSA) |
|---|---|
| Description | Serum PSA was measured at the central laboratory. |
| Time Frame | Baseline and Cycle 2 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics-evaluable population was defined as participants with a baseline and at least 1 post-baseline pharmacodynamics measurement. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 22 | 22 | 23 | 25 | 24 |
| Baseline |
37.588
(48.9413)
|
27.227
(24.8821)
|
97.504
(293.9496)
|
133.238
(189.9345)
|
165.992
(368.5016)
|
100.237
(210.5675)
|
| Cycle 2 Day 1 |
24.325
(46.9725)
|
18.005
(16.9858)
|
38.892
(95.0124)
|
152.940
(261.9735)
|
117.257
(286.1870)
|
56.437
(97.1621)
|
| Title | Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite |
|---|---|
| Description | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
| Time Frame | Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 25 | 24 |
| Orteronel |
1520
(23.9)
|
2210
(33.9)
|
1300
(59.7)
|
1610
(50.3)
|
| Orteronel Metabolite M-I |
272
(33.1)
|
422
(37.0)
|
199
(61.9)
|
261
(47.2)
|
| Title | AUC(0-12): Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours Post-dose for Orteronel and M-I Metabolite |
|---|---|
| Description | AUC(0-12) is measure of area under the curve over the dosing interval where the length of the dosing interval is time 0 to 12 hours in this study. |
| Time Frame | Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 25 | 24 |
| Orteronel |
8810
(16.4)
|
12800
(31.2)
|
7830
(51.1)
|
10200
(41.4)
|
| Orteronel Metabolite M-I |
2130
(28.3)
|
3290
(33.8)
|
1570
(65.5)
|
2080
(44.8)
|
| Title | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite |
|---|---|
| Description | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. |
| Time Frame | Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 25 | 24 |
| Orteronel |
2.97
|
2.43
|
2.00
|
1.92
|
| Orteronel Metabolite M-I |
5.00
|
4.98
|
5.05
|
4.98
|
| Title | AE (0-24) Cumulative Amount of Drug Excreted Into the Urine for Orteronel and MI-Metabolite |
|---|---|
| Description | Cumulative amount of urine excreted time 0 to 24 hour. |
| Time Frame | Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 25 | 24 |
| Orteronel |
115.0
(26.0)
|
164.0
(26.2)
|
95.3
(31.9)
|
161.0
(41.4)
|
| Orteronel Metabolite M-I |
39.6
(31.5)
|
62.5
(26.6)
|
30.0
(40.1)
|
52.8
(46.4)
|
| Title | Cmax,ss: Maximum Observed Plasma Concentration at Steady State for Orteronel and MI-Metabolite |
|---|---|
| Description | Maximum observed steady-state plasma concentration during a dosing interval. |
| Time Frame | Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 25 | 24 |
| Orteronel |
2180
(22.4)
|
3210
(31.5)
|
1840
(37.1)
|
3100
(45.0)
|
| Orteronel Metabolite M-I |
565
(32.4)
|
864
(39.5)
|
485
(75.4)
|
761
(81.3)
|
| Title | 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 |
|---|---|
| Description | Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax at steady state. |
| Time Frame | Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 25 | 24 |
| Orteronel |
2.05
|
2.96
|
2.00
|
1.98
|
| Orteronel Metabolite M-I |
3.08
|
4.78
|
3.00
|
3.00
|
| Title | 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 |
|---|---|
| Description | Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval. |
| Time Frame | Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 25 | 24 |
| Orteronel |
13300
(20.4)
|
20400
(36.1)
|
12600
(36.2)
|
20000
(55.0)
|
| Orteronel Metabolite M-I |
4840
(35.0)
|
7460
(46.3)
|
4340
(69.4)
|
6590
(78.0)
|
| Title | Rac: Accumulation Index for Orteronel and M-I Metabolite |
|---|---|
| Description | Rac was calculated as the ratio of AUCtau to AUC12hr. |
| Time Frame | Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 25 | 24 |
| Orteronel |
1.51
(9.1)
|
1.59
(46.6)
|
1.62
(39.3)
|
1.97
(90.5)
|
| Orteronel Metabolite M-I |
2.27
(17.5)
|
2.26
(43.0)
|
2.76
(45.0)
|
3.17
(77.7)
|
| Title | Ctrough,ss: Observed Predose Plasma Concentration at Steady State for Orteronel and M-I Metabolite |
|---|---|
| Description | Observed predose plasma concentration at steady state. |
| Time Frame | Cycle 1 Day 8 Predose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population included all randomized participants who received orteronel in Cycle 1. |
| Arm/Group Title | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 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. | 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. |
| Measure Participants | 22 | 22 | 24 | 22 |
| Orteronel |
710
(28.1)
|
1060
(63.7)
|
807
(45.4)
|
899
(59.8)
|
| Orteronel Metbolite M-I |
291
(47.1)
|
444
(66.7)
|
314
(68.6)
|
417
(58.0)
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding),symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. |
| Time Frame | From signing of the informed consent form through 30 days after the last dose of study drug, approximately 3.2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population included all randomized participants who received at least one dose of study drug. Adverse events are summarized as per the treatment received. |
| Arm/Group Title | Placebo (Japan) | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Placebo (Ex-Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400 mg (Ex-Japan) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | Orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in Japan and ex-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. | 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 placebo-matching tablets, orally, twice daily in Cycle 1. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | 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. | 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. |
| Measure Participants | 21 | 33 | 32 | 23 | 36 | 36 |
| AE |
7
63.6%
|
33
150%
|
32
320%
|
18
81.8%
|
36
327.3%
|
36
144%
|
| SAE |
0
0%
|
8
36.4%
|
18
180%
|
1
4.5%
|
16
145.5%
|
12
48%
|
Adverse Events
| Time Frame | From signing of the informed consent form through 30 days after the last dose of study drug, approximately 3.2 years. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 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. Adverse events were summarized as per the treatment received. | |||||||||
| Arm/Group Title | Placebo | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400mg (Ex-Japan) | |||||
| Arm/Group Description | Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days). Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study. | Orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in 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, 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 200 mg, tablets, orally, twice daily in 28 day cycles in 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, 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. | |||||
All Cause Mortality |
||||||||||
| Placebo | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400mg (Ex-Japan) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Placebo | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400mg (Ex-Japan) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/44 (22.7%) | 8/33 (24.2%) | 18/32 (56.3%) | 16/36 (44.4%) | 12/36 (33.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 1/44 (2.3%) | 2 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 1/36 (2.8%) | 2 | 0/36 (0%) | 0 |
| Pancytopenia | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Cardiac disorders | ||||||||||
| Cardiac disorder | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Atrial fibrillation | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Coronary Artery Stenosis | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Myocardial Ischaemia | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Cardiac arrest | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Eye disorders | ||||||||||
| Cataract | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Pancreatitis | 1/44 (2.3%) | 1 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Pancreatitis acute | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Duodenal ulcer | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Constipation | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 1/36 (2.8%) | 1 |
| Gastrointestinal haemorrhage | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 1/36 (2.8%) | 1 |
| Large Intestine Polyp | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Nausea | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Vomitting | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Gastrointestinal Angiodysplasia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Diarrhoea | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| General disorders | ||||||||||
| General physical health deterioration | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 2 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Asthenia | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 1/36 (2.8%) | 1 |
| Fatigue | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Device occlusion | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 2 | 0/36 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||
| Hepatic function abnormal | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Cholelithiasis | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Bile Duct Stone | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Infections and infestations | ||||||||||
| Pneumonia | 2/44 (4.5%) | 2 | 0/33 (0%) | 0 | 2/32 (6.3%) | 3 | 2/36 (5.6%) | 2 | 2/36 (5.6%) | 2 |
| Bronchopneumonia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Influenza | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Gastroenteritis viral | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Escherichia sepsis | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Respiratory tract infection | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Septic shock | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Streptococcal bacteraemia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Urinary tract infection | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 1/36 (2.8%) | 1 |
| Sepsis | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Pyelonephritis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Device Related Infection | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||
| Head injury | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Lumbar Vertebral Fracture | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Spinal Compression Fracture | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Thoracic Vertebral Fracture | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Facial Bones Fracture | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Investigations | ||||||||||
| Pancreatic enzymes increased | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Liver function test abnormal | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| International normalised ratio increased | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Metabolism and nutrition disorders | ||||||||||
| Diabetes mellitus | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Diabetic ketoacidosis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Hyponatraemia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Dehydration | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 3/36 (8.3%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Rotator Cuff Syndrome | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Spinal Ligament Ossification | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Lumbar Spinal Stenosis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Pathological Fracture | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 2 | 0/36 (0%) | 0 |
| Arthralgia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 2 | 0/36 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Lung adenocarcinoma | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Cancer pain | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Rectal cancer | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Renal neoplasm | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Gastric cancer | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Lung Neoplasm Malignant | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Pancreatic Carcinoma | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 2 | 0/36 (0%) | 0 |
| Metastatic Pain | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Dizziness | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Balance disorder | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Aphasia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Spinal cord compression | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 1/36 (2.8%) | 1 |
| Altered State Of Consciousness | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Parkinsonism | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Parkinson's disease | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| Haematuria | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 0/36 (0%) | 0 |
| Urinary tract obstruction | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Acute Kidney Injury | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 1/36 (2.8%) | 1 |
| Renal Colic | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Chronic obstructive pulmonary disease | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Pulmonary embolism | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| Pleural effusion | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermatitis exfoliative | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
| Vascular disorders | ||||||||||
| Deep vein thrombosis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Venous thrombosis limb | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Hypertension | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 0/36 (0%) | 0 |
| Orthostatic Hypotension | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 1/36 (2.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Placebo | Orteronel 200 mg (Japan) | Orteronel 300 mg (Japan) | Orteronel 200 mg (Ex-Japan) | Orteronel 400mg (Ex-Japan) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 44/44 (100%) | 33/33 (100%) | 32/32 (100%) | 35/36 (97.2%) | 36/36 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 2/36 (5.6%) | 2 | 0/36 (0%) | 0 |
| Increased tendency to bruise | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Thrombocytopenia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 0/36 (0%) | 0 |
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 3/36 (8.3%) | 3 |
| Sinus tachycardia | 2/44 (4.5%) | 2 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||
| Ear pain | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Endocrine disorders | ||||||||||
| Cushingoid | 0/44 (0%) | 0 | 3/33 (9.1%) | 3 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Eye disorders | ||||||||||
| Cataract | 0/44 (0%) | 0 | 3/33 (9.1%) | 3 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Lacrimation increased | 0/44 (0%) | 0 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Glaucoma | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Gastrointestinal disorders | ||||||||||
| Constipation | 7/44 (15.9%) | 7 | 8/33 (24.2%) | 9 | 10/32 (31.3%) | 12 | 10/36 (27.8%) | 13 | 12/36 (33.3%) | 13 |
| Diarrhoea | 11/44 (25%) | 12 | 4/33 (12.1%) | 4 | 5/32 (15.6%) | 6 | 15/36 (41.7%) | 30 | 13/36 (36.1%) | 16 |
| Nausea | 7/44 (15.9%) | 12 | 5/33 (15.2%) | 6 | 7/32 (21.9%) | 10 | 13/36 (36.1%) | 17 | 12/36 (33.3%) | 16 |
| Vomiting | 3/44 (6.8%) | 3 | 4/33 (12.1%) | 4 | 3/32 (9.4%) | 11 | 9/36 (25%) | 12 | 3/36 (8.3%) | 3 |
| Abdominal discomfort | 4/44 (9.1%) | 4 | 4/33 (12.1%) | 4 | 2/32 (6.3%) | 3 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Abdominal pain upper | 1/44 (2.3%) | 1 | 1/33 (3%) | 1 | 2/32 (6.3%) | 3 | 1/36 (2.8%) | 1 | 4/36 (11.1%) | 4 |
| Abdominal pain | 2/44 (4.5%) | 2 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 4/36 (11.1%) | 4 | 3/36 (8.3%) | 3 |
| Stomatitis | 4/44 (9.1%) | 4 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 2 | 3/36 (8.3%) | 4 | 2/36 (5.6%) | 7 |
| Chronic Gastritis | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Dyspepsia | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 1/36 (2.8%) | 1 | 3/36 (8.3%) | 3 |
| Abdominal distension | 0/44 (0%) | 0 | 2/33 (6.1%) | 3 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Dental caries | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 3 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Pancreatitis | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 2/36 (5.6%) | 2 |
| Mouth ulceration | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 4 |
| Dysphagia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 3 |
| General disorders | ||||||||||
| Fatigue | 8/44 (18.2%) | 9 | 0/33 (0%) | 0 | 2/32 (6.3%) | 3 | 19/36 (52.8%) | 22 | 15/36 (41.7%) | 17 |
| Oedema peripheral | 4/44 (9.1%) | 4 | 8/33 (24.2%) | 10 | 6/32 (18.8%) | 7 | 7/36 (19.4%) | 7 | 5/36 (13.9%) | 6 |
| Malaise | 4/44 (9.1%) | 5 | 4/33 (12.1%) | 5 | 6/32 (18.8%) | 7 | 3/36 (8.3%) | 3 | 0/36 (0%) | 0 |
| Face Oedema | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 3 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Pyrexia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Peripheral swelling | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Hepatobiliary disorders | ||||||||||
| Hepatic function abnormal | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 3/32 (9.4%) | 4 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Immune system disorders | ||||||||||
| Seasonal allergy | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Infections and infestations | ||||||||||
| Nasopharyngitis | 7/44 (15.9%) | 7 | 8/33 (24.2%) | 10 | 8/32 (25%) | 13 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Upper respiratory trat infection | 4/44 (9.1%) | 4 | 3/33 (9.1%) | 4 | 4/32 (12.5%) | 5 | 6/36 (16.7%) | 7 | 2/36 (5.6%) | 2 |
| Bronchitis | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 3 | 1/36 (2.8%) | 5 | 2/36 (5.6%) | 3 |
| Cystitis | 0/44 (0%) | 0 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Influenza | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 2/36 (5.6%) | 2 | 2/36 (5.6%) | 2 |
| Herpes zoster | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Oesophageal candidiasis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Pharyngitis | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Oral candidiasis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 4 | 2/36 (5.6%) | 2 |
| Lower respiratory tract infection | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 4/36 (11.1%) | 6 |
| Sinusitis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Tooth abscess | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 0/36 (0%) | 0 |
| Viral upper respiratory tract infection | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Injury, poisoning and procedural complications | ||||||||||
| Fall | 2/44 (4.5%) | 2 | 3/33 (9.1%) | 4 | 5/32 (15.6%) | 8 | 2/36 (5.6%) | 4 | 5/36 (13.9%) | 6 |
| Contusion | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 3/32 (9.4%) | 3 | 3/36 (8.3%) | 8 | 0/36 (0%) | 0 |
| Rib fracture | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Spinal compression fracture | 0/44 (0%) | 0 | 2/33 (6.1%) | 4 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Skin abrasion | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Thoracic vertebral fracture | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Meniscus injury | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Investigations | ||||||||||
| Lipase increased | 19/44 (43.2%) | 36 | 25/33 (75.8%) | 46 | 19/32 (59.4%) | 32 | 9/36 (25%) | 10 | 7/36 (19.4%) | 9 |
| Amylase increased | 16/44 (36.4%) | 21 | 21/33 (63.6%) | 35 | 19/32 (59.4%) | 27 | 4/36 (11.1%) | 7 | 6/36 (16.7%) | 10 |
| Alanine aminotransferase increased | 6/44 (13.6%) | 7 | 7/33 (21.2%) | 7 | 7/32 (21.9%) | 11 | 2/36 (5.6%) | 4 | 1/36 (2.8%) | 1 |
| Aspartate aminotransferase increased | 6/44 (13.6%) | 8 | 7/33 (21.2%) | 7 | 7/32 (21.9%) | 11 | 2/36 (5.6%) | 4 | 1/36 (2.8%) | 1 |
| Gamma-glutamyltransferase increased | 6/44 (13.6%) | 6 | 5/33 (15.2%) | 6 | 8/32 (25%) | 14 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Weight decreased | 5/44 (11.4%) | 5 | 2/33 (6.1%) | 2 | 6/32 (18.8%) | 9 | 2/36 (5.6%) | 2 | 3/36 (8.3%) | 4 |
| Blood lactate dehydrogenase increased | 5/44 (11.4%) | 5 | 8/33 (24.2%) | 8 | 4/32 (12.5%) | 4 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Blood creatinine increased | 2/44 (4.5%) | 2 | 0/33 (0%) | 0 | 5/32 (15.6%) | 5 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| Blood alkaline phosphatase increased | 1/44 (2.3%) | 1 | 1/33 (3%) | 1 | 6/32 (18.8%) | 7 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Blood urea increased | 1/44 (2.3%) | 2 | 0/33 (0%) | 0 | 4/32 (12.5%) | 8 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| White blood cell count decreased | 3/44 (6.8%) | 5 | 3/33 (9.1%) | 4 | 3/32 (9.4%) | 5 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Weight increased | 0/44 (0%) | 0 | 4/33 (12.1%) | 4 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Neutrophil count decreased | 0/44 (0%) | 0 | 3/33 (9.1%) | 4 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Glycosylated haemoglobin increased | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| White blood cell count increased | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Diabetes mellitus | 5/44 (11.4%) | 5 | 9/33 (27.3%) | 10 | 6/32 (18.8%) | 8 | 1/36 (2.8%) | 1 | 4/36 (11.1%) | 4 |
| Decreased appetite | 5/44 (11.4%) | 7 | 1/33 (3%) | 1 | 5/32 (15.6%) | 8 | 9/36 (25%) | 10 | 7/36 (19.4%) | 8 |
| Hyponatraemia | 4/44 (9.1%) | 4 | 2/33 (6.1%) | 3 | 2/32 (6.3%) | 2 | 1/36 (2.8%) | 1 | 4/36 (11.1%) | 4 |
| Dehydration | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 3 | 4/36 (11.1%) | 5 |
| Hyperglycaemia | 3/44 (6.8%) | 3 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 1/36 (2.8%) | 3 | 2/36 (5.6%) | 2 |
| Hypokalaemia | 2/44 (4.5%) | 2 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 5/36 (13.9%) | 6 | 1/36 (2.8%) | 1 |
| Hyperkalaemia | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 3/32 (9.4%) | 4 | 2/36 (5.6%) | 4 | 2/36 (5.6%) | 2 |
| Type 2 diabetes mellitus | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 4/36 (11.1%) | 5 |
| Hypoglycaemia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Hyperlipidaemia | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Hypercholesterolaemia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 2/36 (5.6%) | 2 |
| Hypomagnesaemia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Muscle spasms | 11/44 (25%) | 16 | 3/33 (9.1%) | 3 | 8/32 (25%) | 9 | 8/36 (22.2%) | 11 | 12/36 (33.3%) | 22 |
| Back pain | 3/44 (6.8%) | 3 | 2/33 (6.1%) | 2 | 3/32 (9.4%) | 3 | 5/36 (13.9%) | 6 | 3/36 (8.3%) | 3 |
| Arthralgia | 2/44 (4.5%) | 3 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 5/36 (13.9%) | 6 | 4/36 (11.1%) | 5 |
| Muscular weakness | 2/44 (4.5%) | 2 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 4/36 (11.1%) | 4 | 4/36 (11.1%) | 4 |
| Musculoskeletal pain | 0/44 (0%) | 0 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 3/36 (8.3%) | 4 | 3/36 (8.3%) | 4 |
| Musculoskeletal chest pain | 2/44 (4.5%) | 2 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 4 | 3/36 (8.3%) | 3 |
| Lumbar spinal stenosis | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Osteoporosis | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 2/36 (5.6%) | 2 | 2/36 (5.6%) | 2 |
| Musculoskeletal discomfort | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 3 | 1/36 (2.8%) | 1 |
| Pain in extremity | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 2 | 2/36 (5.6%) | 2 |
| Myalgia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 4 | 1/36 (2.8%) | 1 |
| Bone pain | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Groin pain | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Cancer pain | 2/44 (4.5%) | 2 | 1/33 (3%) | 1 | 3/32 (9.4%) | 4 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Metastatic pain | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Nervous system disorders | ||||||||||
| Dysgeusia | 3/44 (6.8%) | 3 | 2/33 (6.1%) | 2 | 4/32 (12.5%) | 4 | 4/36 (11.1%) | 4 | 4/36 (11.1%) | 4 |
| Dizziness | 1/44 (2.3%) | 1 | 2/33 (6.1%) | 2 | 4/32 (12.5%) | 5 | 3/36 (8.3%) | 3 | 5/36 (13.9%) | 5 |
| Hypoaesthesia | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 3/32 (9.4%) | 4 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| Somnolence | 0/44 (0%) | 0 | 5/33 (15.2%) | 6 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Headache | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 3/36 (8.3%) | 4 | 1/36 (2.8%) | 2 |
| Paraesthesia | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 3 | 3/36 (8.3%) | 3 |
| Syncope | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 3 |
| Neuropathy peripheral | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| Psychiatric disorders | ||||||||||
| Insomnia | 2/44 (4.5%) | 2 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 2 | 6/36 (16.7%) | 6 | 4/36 (11.1%) | 4 |
| Depression | 1/44 (2.3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 3 | 2/36 (5.6%) | 2 |
| Anxiety | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 2/36 (5.6%) | 2 |
| Restlessness | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Renal and urinary disorders | ||||||||||
| Haematuria | 1/44 (2.3%) | 1 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 3/36 (8.3%) | 4 | 2/36 (5.6%) | 2 |
| Nocturia | 3/44 (6.8%) | 4 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 3 | 1/36 (2.8%) | 1 |
| Dysuria | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Pollakiuria | 0/44 (0%) | 0 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 3/36 (8.3%) | 3 |
| Renal failure | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| Hydronephrosis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 0/36 (0%) | 0 |
| Urinary retention | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnoea | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 3/32 (9.4%) | 3 | 5/36 (13.9%) | 5 | 4/36 (11.1%) | 5 |
| Cough | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 3 | 2/36 (5.6%) | 2 |
| Productive cough | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 0/36 (0%) | 0 |
| Pulmonary embolism | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 0/36 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Rash macular | 3/44 (6.8%) | 3 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 4 | 4/36 (11.1%) | 4 |
| Rash maculo-papular | 0/44 (0%) | 0 | 3/33 (9.1%) | 4 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| Rash erythematous | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Urticaria | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 3/32 (9.4%) | 4 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Purpura | 0/44 (0%) | 0 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Dry skin | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Eczema | 0/44 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Haemorrhage subcutaneous | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/36 (0%) | 0 | 0/36 (0%) | 0 |
| Skin atrophy | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 3 | 1/36 (2.8%) | 2 |
| Ecchymosis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Hyperhidrosis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/36 (5.6%) | 2 | 1/36 (2.8%) | 1 |
| Rash pruritic | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
| Decubitus ulcer | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 3 |
| Rash papular | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 3 |
| Dermatitis acneiform | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/36 (0%) | 0 | 2/36 (5.6%) | 2 |
| Vascular disorders | ||||||||||
| Hot flush | 7/44 (15.9%) | 7 | 3/33 (9.1%) | 3 | 5/32 (15.6%) | 5 | 5/36 (13.9%) | 5 | 10/36 (27.8%) | 10 |
| Hypertension | 4/44 (9.1%) | 4 | 3/33 (9.1%) | 3 | 3/32 (9.4%) | 3 | 2/36 (5.6%) | 2 | 8/36 (22.2%) | 8 |
| Deep vein thrombosis | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 3 | 1/36 (2.8%) | 1 |
| Flushing | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 3/36 (8.3%) | 3 | 1/36 (2.8%) | 1 |
| Hypotension | 0/44 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/36 (2.8%) | 1 | 2/36 (5.6%) | 2 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
| Name/Title | Medical Director, Clinical Science |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01666314
Other Study ID Numbers:
- C21013
- 2012-001539-30
- U1111-1179-5750
First Posted:
Aug 16, 2012
Last Update Posted:
Mar 20, 2018
Last Verified:
Feb 1, 2018