Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02723006
Collaborator
(none)
22
14
3
22.6
1.6
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the initial safety profile and initial antitumor activity of the combination treatments (immune checkpoint inhibitors [nivolumab, ipilimumab] with investigational drugs [TAK-580, TAK-202 (plozalizumab), vedolizumab]) in the 3 arms when administered to participants with advanced melanoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The drugs being tested in this study are called TAK-580, TAK-202 (plozalizumab), and vedolizumab. These investigational drugs were given along with standard of care checkpoint inhibitors ([nivolumab in Arms 1 and 2] or nivolumab + ipilimumab in Arm 3). This study looked at the safety profile of the combination treatments in each arm when administered to participants with metastatic melanoma.
The study planned to enroll approximately 156 participants. Participants were assigned to one of the 3 treatment groups:
-
TAK-580 + nivolumab
-
TAK-202 (plozalizumab) + nivolumab
-
vedolizumab + nivolumab + ipilimumab
This study consists of 3 parts. A dose-escalation safety lead-in phase, confirmatory safety phase and a cohort expansion phase. This multi-center trial will be conducted in the United States. The overall time to participate in this study is 50 weeks. Participants may make multiple visits to the clinic and 30, 60, and 90 days after last dose of study drug for follow-up assessments.
Study Design
Study Type:
Interventional
Actual Enrollment
:
22 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
An Open-Label, Phase 1b, Multi-Arm Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Patients With Advanced Melanoma
Actual Study Start Date
:
Jun 22, 2016
Actual Primary Completion Date
:
May 11, 2018
Actual Study Completion Date
:
May 11, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TAK-580 + nivolumab TAK-580 orally, once weekly along with nivolumab, intravenous, every 2 weeks. |
Drug: TAK-580
TAK-580 tablets
Other Names:
Drug: nivolumab
nivolumab infusion
Other Names:
|
| Experimental: TAK-202 (plozalizumab) + nivolumab TAK-202 (plozalizumab) 2 milligram (mg), intravenous, once in Week 1, 3, 5, 9, and every 4 weeks thereafter with nivolumab infusion, intravenous, every 2 weeks. |
Drug: TAK-202
TAK-202 infusion
Other Names:
Drug: nivolumab
nivolumab infusion
Other Names:
|
| Experimental: vedolizumab + nivolumab + ipilimumab Vedolizumab intravenous, once in Week 1, 3, 5, and 13 along with nivolumab infusion, intravenous, once in Week 1, 4, 7, 10, and 13 and every 2 weeks thereafter, along with ipilimumab intravenous, once in Week 1, 4, 7, and 10. |
Drug: vedolizumab
vedolizumab infusion
Other Names:
Drug: nivolumab
nivolumab infusion
Other Names:
Drug: ipilimumab
ipilimumab infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Dose Limiting Toxicities (DLTs) During the Dose-escalation Safety Lead-in Phase [TAK-580 + Nivolumab and TAK-202 + Nivolumab: Baseline up to Week 9; Vedolizumab + Nivolumab + Ipilimumab: Baseline up to Week 7]
DLTs was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Secondary Outcome Measures
- Overall Response Rate (ORR) During the Dose-escalation Safety Lead-in Phase [Baseline up to Week 50]
ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. was the percentage of participants with complete response (CR) or partial response (PR). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.
- Duration of Response (DOR) During the Dose-escalation Safety Lead-in Phase [From date of first documented confirmed CR/PR until date of first documentation of PD or death (up to Week 50)]
DOR based on RECIST version 1.1 was the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
- Progression-free Survival (PFS) During the Dose-escalation Safety Lead-in Phase [From first dose date to the date of the first documentation of confirmed PD or death (up to Week 50)]
PFS was the time from first dose date to date of the first documentation of confirmed PD or death, whichever occurred first. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions.
- Overall Survival (OS) During the Dose-escalation Safety Lead-in Phase [From first dose of study drug until date of death from any cause (up to Week 50)]
OS was the time from date of first dose of study drug until date of death from any cause.
- Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From the first dose of study drug up to 30 days after the last dose of study drug (up to Week 50)]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Is a male or female participant of 18 years or older.
-
Has histologically confirmed, unresectable Stage III or Stage IV melanoma per the American Joint Committee on Cancer (AJCC) staging system.
-
Has an eastern cooperative oncology group (ECOG) performance status of 0-1.
-
Adequate bone marrow reserve and renal and hepatic function within 28 days before the first dose of study drug on the basis of the defined laboratory parameters.
-
For TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only: Had disease accessible for repeat nonsignificant risk biopsy (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures extending beyond the esophagus, stomach, or bowel) and willingness to undergo serial tumor biopsies.
-
Additional Inclusion Requirements for TAK-580 + nivolumab
- BRAF V600 mutation-positive or NRAS mutation-positive disease previously untreated with RAF, MEK, or other inhibitors of the mitogen-activated protein kinase (MAPK) pathway. Participants who have progressed on these agents can still be enrolled in TAK-202 (plozalizumab) + nivolumab or vedolizumab + nivolumab + ipilimumab.
- Additional Inclusion Requirements for expansion cohorts only a) Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (Version 1.1) and at least 1 nonsignificant risk, non-target lesion accessible for biopsy per the guidelines above (for TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only).
Exclusion Criteria:
-
Has active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (greater than [>] 10 milligram per day [mg/day] prednisone equivalents) for at least 2 weeks prior to study drug administration.
-
Completed a prior therapy less than (<) 2 weeks prior to first dose and for whom adverse events (AEs) related to prior therapy had not returned to baseline or improved to Grade 1.
-
Has active, known or suspected autoimmune disease.
-
Has a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
-
Has a history of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis (including pneumonitis), interstitial lung disease, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
-
Is previously diagnosed human immunodeficiency virus (HIV) infection or active hepatitis B or C.
-
Additional Exclusion Requirements for arm 1 only (nivolumab Plus TAK-580)
-
Concomitant use or administration of clinically significant enzyme inducers less than or equal to (<=) 14 days before the first dose of TAK-580.
-
Treatment with gemfibrozil (or other strong CYP2C8 inhibitor) within 14 days before the first dose of TAK-580.
-
Left ventricular ejection fraction (LVEF) <50 percent (%) as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug.
-
Known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of the TAK-580.
-
Additional Exclusion Requirements for arm 3 only (vedolizumab Plus nivolumab Plus ipilimumab)
-
Had prior exposure to rituximab, natalizumab, vedolizumab, or alemtuzumab.
-
Has a history of any major neurological disorders, including stroke, multiple sclerosis, or neurodegenerative disease.
-
Has taken any live vaccinations within 30 days before study drug administration except for the influenza vaccine.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Arizona Cancer Center | Tucson | Arizona | United States | |
| 2 | University of California Los Angeles - Jonsson Comprehensive Cancer Center | Los Angeles | California | United States | |
| 3 | University of California San Francisco Medical Center | San Francisco | California | United States | |
| 4 | University of Colorado Cancer Center | Aurora | Colorado | United States | |
| 5 | Emory University Hospital | Atlanta | Georgia | United States | |
| 6 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | |
| 7 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | |
| 8 | Virginia Piper Cancer Institute | Minneapolis | Minnesota | United States | |
| 9 | Washington University School of Medicine | Saint Louis | Missouri | United States | |
| 10 | New York University Langone Medical Center | New York | New York | United States | |
| 11 | Saint Luke's Cancer Center - Bethlehem | Easton | Pennsylvania | United States | |
| 12 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | |
| 13 | Texas Oncology-Baylor Charles A. Sammons Cancer Center | Dallas | Texas | United States | |
| 14 | Inova Fairfax Hospital | Fairfax | Virginia | United States |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02723006
Other Study ID Numbers:
- C28003
- U1111-1177-4142
- 2015-005554-35
First Posted:
Mar 30, 2016
Last Update Posted:
Apr 1, 2021
Last Verified:
Mar 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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 10 investigative sites in the United States from 22 June 2016 to 11 May 2018. |
|---|---|
| Pre-assignment Detail | Participants with advanced/metastatic melanoma were enrolled to receive:TAK-580+nivolumab,TAK-202+nivolumab,or vedolizumab+nivolumab+ipilumab. Study was terminated early after the dose escalation safety-lead in phase due to lack of enrollment(Arm 1), lack of clinical benefit(Arm 2), and after pre-specified stopping rule for diarrhea was met(Arm 3). |
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab |
|---|---|---|---|
| Arm/Group Description | Participants in this group received TAK-580 400 milligram (mg), tablets, orally, once weekly along with nivolumab 3 milligram per kilogram (mg/kg), infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). |
| Period Title: Overall Study | |||
| STARTED | 1 | 9 | 12 |
| COMPLETED | 0 | 2 | 5 |
| NOT COMPLETED | 1 | 7 | 7 |
Baseline Characteristics
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). | Total of all reporting groups |
| Overall Participants | 1 | 9 | 12 | 22 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
41
|
63.9
(11.54)
|
55.8
(16.36)
|
58.5
(14.90)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
1
100%
|
3
33.3%
|
7
58.3%
|
11
50%
|
| Male |
0
0%
|
6
66.7%
|
5
41.7%
|
11
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
1
100%
|
9
100%
|
9
75%
|
19
86.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
3
25%
|
3
13.6%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
11.1%
|
0
0%
|
1
4.5%
|
| White |
1
100%
|
8
88.9%
|
11
91.7%
|
20
90.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
8.3%
|
1
4.5%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
1
100%
|
9
100%
|
12
100%
|
22
100%
|
| Height (centimeter (cm)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [centimeter (cm)] |
171.00
|
168.49
(10.479)
|
170.00
(10.846)
|
169.40
(10.170)
|
| Weight (kilogram (kg)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kilogram (kg)] |
77.80
|
77.42
(9.248)
|
88.20
(26.786)
|
83.32
(20.937)
|
Outcome Measures
| Title | Number of Dose Limiting Toxicities (DLTs) During the Dose-escalation Safety Lead-in Phase |
|---|---|
| Description | DLTs was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. |
| Time Frame | TAK-580 + Nivolumab and TAK-202 + Nivolumab: Baseline up to Week 9; Vedolizumab + Nivolumab + Ipilimumab: Baseline up to Week 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants who received at least 1 dose, even if incomplete, of study treatment (TAK-580, TAK-202, or vedolizumab). |
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab |
|---|---|---|---|
| Arm/Group Description | Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). |
| Measure Participants | 1 | 9 | 12 |
| Number [DLTs] |
0
|
3
|
0
|
| Title | Overall Response Rate (ORR) During the Dose-escalation Safety Lead-in Phase |
|---|---|
| Description | ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. was the percentage of participants with complete response (CR) or partial response (PR). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD. |
| Time Frame | Baseline up to Week 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Planned efficacy analyses was not performed as the study was terminated due to lack of enrollment, lack of clinical benefit and after the pre-specified stopping rule was met for diarrhea. |
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab |
|---|---|---|---|
| Arm/Group Description | Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). |
| Measure Participants | 0 | 0 | 0 |
| Title | Duration of Response (DOR) During the Dose-escalation Safety Lead-in Phase |
|---|---|
| Description | DOR based on RECIST version 1.1 was the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Time Frame | From date of first documented confirmed CR/PR until date of first documentation of PD or death (up to Week 50) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Planned efficacy analyses was not performed as the study was terminated due to lack of enrollment, lack of clinical benefit and after the pre-specified stopping rule was met for diarrhea. |
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab |
|---|---|---|---|
| Arm/Group Description | Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). |
| Measure Participants | 0 | 0 | 0 |
| Title | Progression-free Survival (PFS) During the Dose-escalation Safety Lead-in Phase |
|---|---|
| Description | PFS was the time from first dose date to date of the first documentation of confirmed PD or death, whichever occurred first. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. |
| Time Frame | From first dose date to the date of the first documentation of confirmed PD or death (up to Week 50) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Planned efficacy analyses was not performed as the study was terminated due to lack of enrollment, lack of clinical benefit and after the pre-specified stopping rule was met for diarrhea. |
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab |
|---|---|---|---|
| Arm/Group Description | Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). |
| Measure Participants | 0 | 0 | 0 |
| Title | Overall Survival (OS) During the Dose-escalation Safety Lead-in Phase |
|---|---|
| Description | OS was the time from date of first dose of study drug until date of death from any cause. |
| Time Frame | From first dose of study drug until date of death from any cause (up to Week 50) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Planned efficacy analyses was not performed as the study was terminated due to lack of enrollment, lack of clinical benefit and after the pre-specified stopping rule was met for diarrhea. |
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab |
|---|---|---|---|
| Arm/Group Description | Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). |
| Measure Participants | 0 | 0 | 0 |
| Title | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | |
| Time Frame | From the first dose of study drug up to 30 days after the last dose of study drug (up to Week 50) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants who received at least 1 dose, even if incomplete, of study treatment (TAK-580, TAK-202, or vedolizumab). |
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab |
|---|---|---|---|
| Arm/Group Description | Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). |
| Measure Participants | 1 | 9 | 12 |
| TEAEs |
1
100%
|
9
100%
|
12
100%
|
| SAEs |
1
100%
|
2
22.2%
|
7
58.3%
|
Adverse Events
| Time Frame | Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (up to Week 50) after the last dose of study drug | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||||
| Arm/Group Title | Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab | |||
| Arm/Group Description | Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). | Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). | Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). | |||
All Cause Mortality |
||||||
| Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | 0/9 (0%) | 2/12 (16.7%) | |||
Serious Adverse Events |
||||||
| Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | 2/9 (22.2%) | 7/12 (58.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Eosinophilia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Leukocytosis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Cardiac disorders | ||||||
| Acute coronary syndrome | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 |
| Endocrine disorders | ||||||
| Adrenal insufficiency | 1/1 (100%) | 1 | 0/9 (0%) | 0 | 0/12 (0%) | 0 |
| Hypophysitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Gastrointestinal disorders | ||||||
| Nausea | 1/1 (100%) | 1 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Autoimmune colitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Colitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Diarrhoea | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 |
| Rectal haemorrhage | 0/1 (0%) | 0 | 1/9 (11.1%) | 2 | 0/12 (0%) | 0 |
| General disorders | ||||||
| Pyrexia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||||
| Appendicitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Spinal compression fracture | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 |
| Investigations | ||||||
| International normalised ratio increased | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Metastatic malignant melanoma | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Arm 1: TAK-580 + Nivolumab | Arm 2: TAK-202 + Nivolumab | Arm 3: Vedolizumab + Ipilimumab + Nivolumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | 9/9 (100%) | 12/12 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 4/12 (33.3%) | 7 |
| Eosinophilia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Leukocytosis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Thrombocytopenia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Cardiac disorders | ||||||
| Atrial fibrillation | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Palpitations | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Sinus tachycardia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 3 |
| Ear and labyrinth disorders | ||||||
| Tinnitus | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
| Ear discomfort | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Endocrine disorders | ||||||
| Hypothyroidism | 0/1 (0%) | 0 | 4/9 (44.4%) | 5 | 3/12 (25%) | 3 |
| Adrenal insufficiency | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 4/12 (33.3%) | 4 |
| Hyperthyroidism | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 3/12 (25%) | 3 |
| Eye disorders | ||||||
| Conjunctivitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Conjunctivitis allergic | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dry eye | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Vision blurred | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Visual impairment | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Gastrointestinal disorders | ||||||
| Nausea | 1/1 (100%) | 3 | 6/9 (66.7%) | 7 | 8/12 (66.7%) | 10 |
| Diarrhoea | 0/1 (0%) | 0 | 3/9 (33.3%) | 5 | 5/12 (41.7%) | 12 |
| Abdominal pain | 0/1 (0%) | 0 | 3/9 (33.3%) | 4 | 4/12 (33.3%) | 8 |
| Constipation | 0/1 (0%) | 0 | 2/9 (22.2%) | 3 | 3/12 (25%) | 4 |
| Dry mouth | 1/1 (100%) | 1 | 1/9 (11.1%) | 2 | 2/12 (16.7%) | 2 |
| Vomiting | 1/1 (100%) | 6 | 2/9 (22.2%) | 3 | 1/12 (8.3%) | 2 |
| Oropharyngeal pain | 0/1 (0%) | 0 | 2/9 (22.2%) | 2 | 1/12 (8.3%) | 1 |
| Oral pain | 1/1 (100%) | 1 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Abdominal discomfort | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Abdominal distension | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Anorectal disorder | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Autoimmune colitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Duodenitis | 1/1 (100%) | 1 | 0/9 (0%) | 0 | 0/12 (0%) | 0 |
| Dyspepsia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dysphagia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Eosinophilic oesophagitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Gastrooesophageal reflux disease | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Gingival bleeding | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Rectal haemorrhage | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Stomatitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| General disorders | ||||||
| Fatigue | 1/1 (100%) | 2 | 4/9 (44.4%) | 8 | 9/12 (75%) | 12 |
| Pyrexia | 1/1 (100%) | 1 | 3/9 (33.3%) | 5 | 5/12 (41.7%) | 9 |
| Chills | 0/1 (0%) | 0 | 4/9 (44.4%) | 5 | 0/12 (0%) | 0 |
| Influenza like illness | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 2/12 (16.7%) | 2 |
| Oedema peripheral | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Facial pain | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Gait disturbance | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Infusion site reaction | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Localised oedema | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Thirst | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Autoimmune hepatitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Immune-mediated hepatitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Immune system disorders | ||||||
| Drug hypersensitivity | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Seasonal allergy | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||||
| Candida infection | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Skin infection | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Urinary tract infection | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Acarodermatitis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Bacterascites | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Bacterial infection | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Cellulitis | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Influenza | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Incision site haemorrhage | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 0/1 (0%) | 0 | 2/9 (22.2%) | 4 | 2/12 (16.7%) | 4 |
| Aspartate aminotransferase increased | 0/1 (0%) | 0 | 2/9 (22.2%) | 3 | 1/12 (8.3%) | 1 |
| Amylase increased | 1/1 (100%) | 1 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Weight decreased | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Blood alkaline phosphatase increased | 0/1 (0%) | 0 | 1/9 (11.1%) | 2 | 0/12 (0%) | 0 |
| Eosinophil percentage increased | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Heart rate increased | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Lipase increased | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Neutrophil count decreased | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Platelet count decreased | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Thyroid function test abnormal | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| White blood cell count decreased | 0/1 (0%) | 0 | 1/9 (11.1%) | 2 | 0/12 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/1 (0%) | 0 | 3/9 (33.3%) | 4 | 2/12 (16.7%) | 2 |
| Dehydration | 1/1 (100%) | 1 | 0/9 (0%) | 0 | 3/12 (25%) | 3 |
| Hypokalaemia | 1/1 (100%) | 1 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hyponatraemia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
| Hyperglycaemia | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Hyperkalaemia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 |
| Hyperuricaemia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypoalbuminaemia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 |
| Hypocalcaemia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 |
| Hypoglycaemia | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/1 (100%) | 1 | 2/9 (22.2%) | 4 | 2/12 (16.7%) | 2 |
| Back pain | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 3/12 (25%) | 3 |
| Muscular weakness | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
| Musculoskeletal chest pain | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
| Myalgia | 0/1 (0%) | 0 | 2/9 (22.2%) | 2 | 0/12 (0%) | 0 |
| Neck pain | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Arthritis | 0/1 (0%) | 0 | 1/9 (11.1%) | 3 | 0/12 (0%) | 0 |
| Joint swelling | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Muscle spasms | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Musculoskeletal pain | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Pain in extremity | 1/1 (100%) | 1 | 0/9 (0%) | 0 | 0/12 (0%) | 0 |
| Nervous system disorders | ||||||
| Headache | 1/1 (100%) | 1 | 3/9 (33.3%) | 4 | 5/12 (41.7%) | 10 |
| Dizziness | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Ataxia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dysgeusia | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Neuropathy peripheral | 1/1 (100%) | 1 | 0/9 (0%) | 0 | 0/12 (0%) | 0 |
| Paraesthesia | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Peripheral motor neuropathy | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Tremor | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Psychiatric disorders | ||||||
| Insomnia | 0/1 (0%) | 0 | 1/9 (11.1%) | 2 | 1/12 (8.3%) | 1 |
| Anxiety | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Depression | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hallucination, visual | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Mental status changes | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 1/1 (100%) | 1 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dysuria | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Micturition frequency decreased | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Nephrolithiasis | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Pollakiuria | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/1 (0%) | 0 | 3/9 (33.3%) | 3 | 4/12 (33.3%) | 4 |
| Dyspnoea | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 2/12 (16.7%) | 3 |
| Nasal congestion | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 3/12 (25%) | 3 |
| Epistaxis | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Productive cough | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Rhinorrhoea | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Sinus congestion | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Pruritus | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 6/12 (50%) | 10 |
| Rash | 0/1 (0%) | 0 | 1/9 (11.1%) | 4 | 4/12 (33.3%) | 4 |
| Rash maculo-papular | 0/1 (0%) | 0 | 2/9 (22.2%) | 2 | 3/12 (25%) | 3 |
| Dermatitis acneiform | 1/1 (100%) | 3 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Hyperhidrosis | 0/1 (0%) | 0 | 2/9 (22.2%) | 4 | 0/12 (0%) | 0 |
| Night sweats | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Dry skin | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 |
| Hypohidrosis | 0/1 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Pruritus generalised | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Rash erythematous | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Rash papular | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Rash pruritic | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Vascular disorders | ||||||
| Hypotension | 0/1 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02723006
Other Study ID Numbers:
- C28003
- U1111-1177-4142
- 2015-005554-35
First Posted:
Mar 30, 2016
Last Update Posted:
Apr 1, 2021
Last Verified:
Mar 1, 2021