Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00932698
Collaborator
(none)
60
5
11
91.3
12
0.1
Study Details
Study Description
Brief Summary
This study will determine the safety profile, tolerability, and maximum tolerated dose (MTD) and disease response of Ixazomib administered orally in participants with relapsed and/or refractory multiple myeloma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The drug being tested in this study is ixazomib. Ixazomib is being tested to treat people who have multiple myeloma. This study will look at the safety and efficacy of ixazomib and will enroll approximately 60 participants.
Participants will receive ixazomib by oral capsule twice weekly on Days 1, 4, 8, and 11 of a 21-day cycle. The study will consist of a dose escalation phase to determine the MTD, followed by an expansion phase in which participants will be treated at the MTD.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is 8 years.
Study Design
Study Type:
Interventional
Actual Enrollment
:
60 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Form of Ixazomib (MLN9708), a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
Actual Study Start Date
:
Oct 12, 2009
Actual Primary Completion Date
:
Jun 20, 2013
Actual Study Completion Date
:
May 23, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Relapsed and Refractory Expansion Cohort: Ixazomib 2 mg/m^2 Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor (Up to 550 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
| Experimental: Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
Drug: Ixazomib
Ixazomib capsules
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)]
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death;is life-threatening;requires inpatient hospitalization or prolongation of present hospitalization;results in persistent or significant disability/incapacity;is a congenital anomaly/birth defect;or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.
- Number of Participants With Clinically Significant Abnormalities Reported as TEAEs [From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)]
The number of participants with any clinically significant abnormal standard safety laboratory values collected throughout the study reported as TEAEs. Parameters assessed were hematology, serum chemistry and urinalysis.
- Number of Participants With a TEAE of Peripheral Neuropathy [From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)]
Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy.
- Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs [From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)]
The number of participants with any clinically significant changes in vital signs collected throughout the study that were reported as TEAEs. Measurement of vital signs, included oral temperature, blood pressure, and heart rate.
- Maximum Tolerated Dose (MTD) of Ixazomib [Cycle 1 (21 days)]
MTD was highest dose of Ixazomib, at which <=1 of 6 participants experienced dose-limiting toxicity (DLT) during Cycle 1 of Phase 1. DLT was defined as any of following considered possibly related to therapy: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days;Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia (platelets < 25,000/mm^3) for >7 days;Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or >=Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy; Grade 3 QTc prolongation (QTc >500 millisecond [msec]);any >=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia; or <1 week Grade 3 fatigue; delay in initiation of the subsequent therapy cycle by >2 weeks; other >=Grade 2 study drug-related nonhematologic toxicities requiring therapy discontinuation.
- Recommended Phase 2 Dose (RP2D) of Ixazomib [Cycle 1 through Cycle 39 (Up to 28.3 months)]
The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK) and pharmacodynamic data observed in Cycle 1 and beyond.
Secondary Outcome Measures
- Cmax: Maximum Observed Plasma Concentration for Ixazomib [Cycle 1, Days 1 and 11: Predose and at multiple time points (up to 264 hours) postdose]
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib [Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose]
- AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib [Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose]
- AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib [Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose]
- λz: Terminal Disposition Phase Rate Constant for Ixazomib [Cycle 1, Day 11: predose and at multiple time points (Up to 264 hours) postdose]
- T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib [Cycle 1, Day 11: predose and at multiple time points (up to 264 hours) postdose]
- CL/F: Blood Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Ixazomib [Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose]
CL/F is apparent clearance of the drug from the plasma.
- Emax: Maximum Observed Effect for Ixazomib [Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose]
Emax was determined to characterize the whole blood 20S proteasome inhibition parameters.
- TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib [Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose]
TEmax was determined to characterize the whole blood 20S proteasome inhibition parameters.
- Overall Response Rate (ORR) [Cycle 1 through Cycle 115 (Up to 80.1 months)]
ORR is defined as percentage of participants with complete response (CR) or partial response (PR) or minimal response (MR) as assessed by the investigator using International Myeloma Working Group Uniform Response criteria. CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg /24 h. MR=25-49% reduction in the serum monoclonal paraprotein maintained for a minimum of 6 weeks; 50-89% reduction in 24-h urinary light chain excretion, which still exceeds 200 mg/24 h, maintained for a minimum of 6 weeks; for participants with non-secretory myeloma only, 25-49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks; 25-49% reduction in the size of soft tissue plasmacytomas; no increase in the size or number of lytic bone lesions.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Each participant must meet all of the following inclusion criteria to be enrolled in the study:
-
Multiple myeloma diagnosed according to the standard criteria.
-
Participants with multiple myeloma who have relapsed following at least 2 lines of therapy.
-
Participants must have measurable disease.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
-
Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
-
Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.
-
Voluntary written consent.
-
Suitable venous access for study-required blood sampling.
Exclusion Criteria:
Participants meeting any of the following exclusion criteria are not to be enrolled in the study:
-
Peripheral neuropathy greater than or equal to (>=) Grade 2.
-
Female participants who are lactating or have a positive serum pregnancy test during the screening period.
-
Major surgery within 14 days before the first dose of study drug.
-
Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
-
Life-threatening illness unrelated to cancer.
-
Diarrhea > Grade 1, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.
-
Systemic antineoplastic or radiation therapy within 14 days of cytotoxic agents within 21 days before the first dose of study treatment.
-
Treatment with any investigational products within 21 days before the first dose of study treatment.
-
Treatment with any investigational proteasome inhibitor.
-
Systemic treatment with prohibited medication.
-
Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent per day. Inhaled and topical steroids are permitted.
-
Central nervous system involvement.
-
Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months.
-
Corrected QT interval (QTc) > 470 milliseconds on a 12-lead electrocardiogram (ECG) obtained during the screening period.
-
Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
-
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
-
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption of tolerance of ixazomib including difficulty swallowing.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | H. Lee Moffitt Cancer Center | Tampa | Florida | United States | 33617 |
| 2 | Emory University | Atlanta | Georgia | United States | 30322 |
| 3 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 4 | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48109 |
| 5 | M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
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:
NCT00932698
Other Study ID Numbers:
- C16003
- U1111-1177-7936
First Posted:
Jul 3, 2009
Last Update Posted:
Aug 7, 2019
Last Verified:
Jun 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Millennium Pharmaceuticals, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 5 investigative sites in the United States from 12 October 2009 to 23 May 2017. |
|---|---|
| Pre-assignment Detail | 60 participants with a diagnosis of relapsed and/or refractory (RR) multiple myeloma were enrolled in 1 of 7 ixazomib dose escalation groups (26 participants) and/or 1 of 4 ixazomib dose expansion groups (40 participants). 6 Participants in 2.0 mg/m^2 dose escalation cohort were also included in the expansion group: 5 in RR, 1 in VR arms. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor (Up to 550 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Period Title: Part 1 (Dose Escalation) | |||||||||||
| STARTED | 3 | 3 | 3 | 3 | 3 | 7 | 4 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 3 | 3 | 3 | 3 | 7 | 4 | 0 | 0 | 0 | 0 |
| Period Title: Part 1 (Dose Escalation) | |||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 20 | 12 | 6 | 2 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 20 | 12 | 6 | 2 |
Baseline Characteristics
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor (Up to 550 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). | Total of all reporting groups |
| Overall Participants | 3 | 3 | 3 | 3 | 3 | 1 | 4 | 20 | 12 | 6 | 2 | 60 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||||||
| Mean (Standard Deviation) [years] |
65.3
(7.02)
|
61.3
(6.81)
|
69.3
(12.10)
|
66.0
(7.00)
|
64.0
(9.85)
|
78
(NA)
|
64.3
(7.50)
|
64.4
(9.58)
|
65.4
(8.02)
|
64.0
(6.84)
|
71.5
(3.54)
|
65.2
(8.25)
|
| Sex: Female, Male (Count of Participants) | ||||||||||||
| Female |
1
33.3%
|
1
33.3%
|
1
33.3%
|
1
33.3%
|
1
33.3%
|
0
0%
|
2
50%
|
12
60%
|
6
50%
|
1
16.7%
|
2
100%
|
28
46.7%
|
| Male |
2
66.7%
|
2
66.7%
|
2
66.7%
|
2
66.7%
|
2
66.7%
|
1
100%
|
2
50%
|
8
40%
|
6
50%
|
5
83.3%
|
0
0%
|
32
53.3%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||||||
| Hispanic or Latino |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
25%
|
0
0%
|
0
0%
|
4
6.7%
|
| Not Hispanic or Latino |
3
100%
|
2
66.7%
|
2
66.7%
|
3
100%
|
3
100%
|
1
100%
|
4
100%
|
20
100%
|
9
75%
|
6
100%
|
2
100%
|
55
91.7%
|
| Missing |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.7%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||||||
| White |
3
100%
|
2
66.7%
|
3
100%
|
3
100%
|
1
33.3%
|
1
100%
|
3
75%
|
18
90%
|
12
100%
|
6
100%
|
2
100%
|
54
90%
|
| Black or African American |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
2
66.7%
|
0
0%
|
1
25%
|
1
5%
|
0
0%
|
0
0%
|
0
0%
|
5
8.3%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5%
|
0
0%
|
0
0%
|
0
0%
|
1
1.7%
|
| Region of Enrollment (Count of Participants) | ||||||||||||
| United States |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
1
100%
|
4
100%
|
20
100%
|
12
100%
|
6
100%
|
2
100%
|
60
100%
|
| Height (centimeter (cm)) [Mean (Standard Deviation) ] | ||||||||||||
| Mean (Standard Deviation) [centimeter (cm)] |
173.1
(9.63)
|
167.5
(7.60)
|
167.4
(4.54)
|
180.1
(14.25)
|
165.4
(7.90)
|
178
(NA)
|
169.7
(12.18)
|
165.8
(11.28)
|
165.7
(13.26)
|
169.3
(9.16)
|
156.7
(6.08)
|
167.5
(11.07)
|
| Weight (kilogram (kg)) [Mean (Standard Deviation) ] | ||||||||||||
| Mean (Standard Deviation) [kilogram (kg)] |
87.50
(12.560)
|
71.03
(5.937)
|
74.87
(5.036)
|
109.90
(12.760)
|
80.77
(2.542)
|
82.3
(NA)
|
82.98
(21.532)
|
77.81
(23.760)
|
72.60
(15.579)
|
93.20
(16.811)
|
71.70
(36.770)
|
80.27
(19.946)
|
| Body Surface Area (meter square) [Mean (Standard Deviation) ] | ||||||||||||
| Mean (Standard Deviation) [meter square] |
2.05
(0.192)
|
1.82
(0.100)
|
1.86
(0.062)
|
2.34
(0.229)
|
1.93
(0.071)
|
2.02
(NA)
|
1.97
(0.335)
|
1.88
(0.342)
|
1.82
(0.237)
|
2.09
(0.265)
|
1.74
(0.495)
|
1.92
(0.291)
|
| Time Since Primary Diagnosis to First Dose (months) [Median (Full Range) ] | ||||||||||||
| Median (Full Range) [months] |
59.1
|
61.8
|
45.8
|
80.4
|
38.4
|
44.62
|
35.2
|
56.9
|
42.7
|
71.9
|
76.1
|
57.4
|
Outcome Measures
| Title | Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death;is life-threatening;requires inpatient hospitalization or prolongation of present hospitalization;results in persistent or significant disability/incapacity;is a congenital anomaly/birth defect;or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. |
| Time Frame | From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received at least 1 dose of ixazomib. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 3 | 3 | 3 | 3 | 3 | 7 | 4 | 20 | 12 | 6 | 2 |
| AEs |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
7
700%
|
4
100%
|
20
100%
|
12
100%
|
6
100%
|
2
100%
|
| SAEs |
0
0%
|
0
0%
|
2
66.7%
|
2
66.7%
|
0
0%
|
5
500%
|
3
75%
|
14
70%
|
6
50%
|
3
50%
|
2
100%
|
| Title | Number of Participants With Clinically Significant Abnormalities Reported as TEAEs |
|---|---|
| Description | The number of participants with any clinically significant abnormal standard safety laboratory values collected throughout the study reported as TEAEs. Parameters assessed were hematology, serum chemistry and urinalysis. |
| Time Frame | From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received at least 1 dose of ixazomib. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 3 | 3 | 3 | 3 | 3 | 7 | 4 | 20 | 12 | 6 | 2 |
| Blood Creatinine Increased |
1
33.3%
|
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
1
100%
|
1
25%
|
2
10%
|
2
16.7%
|
0
0%
|
0
0%
|
| Blood Urea Increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
1
16.7%
|
0
0%
|
| White Blood Cell Count Decreased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Neutrophil Count Decreased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
| Alanine Aminotransferase Increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5%
|
0
0%
|
0
0%
|
0
0%
|
| Liver Function Test Increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5%
|
0
0%
|
0
0%
|
0
0%
|
| Blood Calcium Increased |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Platelet Count Decreased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Haematocrit Decreased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
| Haemoglobin Decreased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
| Title | Number of Participants With a TEAE of Peripheral Neuropathy |
|---|---|
| Description | Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy. |
| Time Frame | From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received at least 1 dose of ixazomib. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 3 | 3 | 3 | 3 | 3 | 7 | 4 | 20 | 12 | 6 | 2 |
| Neuropathy Peripheral |
0
0%
|
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
1
100%
|
0
0%
|
3
15%
|
3
25%
|
1
16.7%
|
0
0%
|
| Peripheral Sensory Neuropathy |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs |
|---|---|
| Description | The number of participants with any clinically significant changes in vital signs collected throughout the study that were reported as TEAEs. Measurement of vital signs, included oral temperature, blood pressure, and heart rate. |
| Time Frame | From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received at least 1 dose of ixazomib. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 3 | 3 | 3 | 3 | 3 | 7 | 4 | 20 | 12 | 6 | 2 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Maximum Tolerated Dose (MTD) of Ixazomib |
|---|---|
| Description | MTD was highest dose of Ixazomib, at which <=1 of 6 participants experienced dose-limiting toxicity (DLT) during Cycle 1 of Phase 1. DLT was defined as any of following considered possibly related to therapy: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days;Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia (platelets < 25,000/mm^3) for >7 days;Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or >=Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy; Grade 3 QTc prolongation (QTc >500 millisecond [msec]);any >=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia; or <1 week Grade 3 fatigue; delay in initiation of the subsequent therapy cycle by >2 weeks; other >=Grade 2 study drug-related nonhematologic toxicities requiring therapy discontinuation. |
| Time Frame | Cycle 1 (21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT-evaluable population was defined as all participants who received all Cycle 1 doses of ixazomib and completed Cycle 1 or who experienced DLT in Cycle 1. |
| Arm/Group Title | Ixazomib (All Groups) |
|---|---|
| Arm/Group Description | All participants who received ixazomib 0.24 mg/m^2, 0.48 mg/m^2, 0.8 mg/m^2, 1.2 mg/m^2, 1.68 mg/m^2, 2 mg/m^2 or 2.23 mg/m^2 in dose-escalation cohorts. |
| Measure Participants | 26 |
| Number [mg/m^2] |
2
|
| Title | Recommended Phase 2 Dose (RP2D) of Ixazomib |
|---|---|
| Description | The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK) and pharmacodynamic data observed in Cycle 1 and beyond. |
| Time Frame | Cycle 1 through Cycle 39 (Up to 28.3 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received at least 1 dose of ixazomib. |
| Arm/Group Title | Ixazomib (All Groups) |
|---|---|
| Arm/Group Description | All participants who received ixazomib 0.24 mg/m^2, 0.48 mg/m^2, 0.8 mg/m^2, 1.2 mg/m^2, 1.68 mg/m^2, 2 mg/m^2 or 2.23 mg/m^2 in dose-escalation cohorts. |
| Measure Participants | 26 |
| Number [mg/m^2] |
2
|
| Title | Cmax: Maximum Observed Plasma Concentration for Ixazomib |
|---|---|
| Description | |
| Time Frame | Cycle 1, Days 1 and 11: Predose and at multiple time points (up to 264 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 3 | 3 | 2 | 2 | 3 | 6 | 3 | 17 | 9 | 6 | 1 |
| Day 1 |
2.120
(0.3974)
|
10.190
(2.5597)
|
22.200
(11.3137)
|
29.000
(24.1831)
|
21.100
(10.1237)
|
68.167
(34.7876)
|
117.933
(67.1924)
|
58.900
(36.1337)
|
59.343
(41.9853)
|
85.600
(58.8496)
|
26.600
(NA)
|
| Day 11 |
2.837
(1.5051)
|
8.857
(5.5598)
|
31.650
(15.2028)
|
56.500
(14.1421)
|
101.100
(71.3597)
|
85.420
(30.7632)
|
105.450
(41.7900)
|
59.871
(32.5851)
|
61.800
(24.8780)
|
109.660
(27.5668)
|
27.200
(NA)
|
| Title | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib |
|---|---|
| Description | |
| Time Frame | Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 3 | 3 | 2 | 2 | 3 | 6 | 3 | 17 | 9 | 6 | 1 |
| Day 1 |
1.000
|
1.000
|
0.775
|
0.775
|
1.000
|
1.000
|
1.000
|
1.000
|
0.617
|
0.525
|
1.000
|
| Day 11 |
1.100
|
1.000
|
1.275
|
0.500
|
1.000
|
0.667
|
0.832
|
1.010
|
0.583
|
1.500
|
1.500
|
| Title | AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib |
|---|---|
| Description | |
| Time Frame | Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 3 | 3 | 2 | 2 | 3 | 6 | 3 | 17 | 9 | 6 | 1 |
| Day 1 |
3.383
(1.7210)
|
20.700
(4.5255)
|
109.000
(41.0122)
|
159.050
(91.8532)
|
251.000
(62.5060)
|
449.000
(185.9516)
|
416.500
(47.3762)
|
418.175
(218.7115)
|
351.000
(141.4337)
|
410.000
(138.7732)
|
509.000
(NA)
|
| Day 11 |
56.533
(15.5095)
|
177.667
(115.6820)
|
458.000
(42.4264)
|
605.000
(NA)
|
808.500
(212.8391)
|
1435.600
(1027.3881)
|
1915.000
(148.4924)
|
903.846
(382.9033)
|
937.857
(334.2082)
|
2297.200
(1137.8221)
|
1010.000
(NA)
|
| Title | AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib |
|---|---|
| Description | |
| Time Frame | Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 3 | 3 | 2 | 2 | 3 | 6 | 3 | 17 | 9 | 6 | 1 |
| Day 1 |
109.00
(41.012)
|
159.05
(91.853)
|
251.00
(62.506)
|
449.00
(185.952)
|
416.50
(47.376)
|
451.64
(194.522)
|
351.00
(141.434)
|
410.00
(138.773)
|
509.00
(NA)
|
||
| Day 11 |
56.53
(15.509)
|
177.67
(115.682)
|
458.00
(42.426)
|
605.00
(NA)
|
808.50
(212.839)
|
1435.60
(1027.388)
|
1915.00
(148.492)
|
903.85
(382.903)
|
937.86
(334.208)
|
2297.20
(1137.822)
|
1010.00
(NA)
|
| Title | λz: Terminal Disposition Phase Rate Constant for Ixazomib |
|---|---|
| Description | |
| Time Frame | Cycle 1, Day 11: predose and at multiple time points (Up to 264 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 0 | 1 | 0 | 2 | 3 | 5 | 2 | 11 | 7 | 4 | 1 |
| Mean (Standard Deviation) [1/hr] |
0.005
(NA)
|
0.005
(0.0001)
|
0.006
(0.0012)
|
0.007
(0.0012)
|
0.008
(0.0007)
|
0.006
(0.0015)
|
0.006
(0.0018)
|
0.006
(0.0020)
|
0.005
(NA)
|
| Title | T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib |
|---|---|
| Description | |
| Time Frame | Cycle 1, Day 11: predose and at multiple time points (up to 264 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 0 | 1 | 0 | 2 | 3 | 5 | 2 | 11 | 7 | 4 | 1 |
| Mean (Standard Deviation) [hr] |
135.00
(NA)
|
126.50
(2.121)
|
129.33
(25.658)
|
105.88
(21.071)
|
92.70
(8.485)
|
115.85
(26.368)
|
123.06
(33.877)
|
124.93
(41.330)
|
134.00
(NA)
|
| Title | CL/F: Blood Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Ixazomib |
|---|---|
| Description | CL/F is apparent clearance of the drug from the plasma. |
| Time Frame | Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| CL/F was not reported as this PK parameter could not be calculated. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Emax: Maximum Observed Effect for Ixazomib |
|---|---|
| Description | Emax was determined to characterize the whole blood 20S proteasome inhibition parameters. |
| Time Frame | Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data is reported due to concerns about the third-party laboratory's performance of the 20S assay that precluded the ability to confirm the accuracy of the data generated. The data was not considered reliable. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | VELCADE-Relapsed Expansion Cohort: MLN9708 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib (MLN9708) 2 mg/m^2 (MTD), capsule, orally, twice weekly on Days 1, 4, 8 and 11 in 21-day treatment cycles until PD or unacceptable toxicity in participants with relapsed multiple myeloma previously treated with VELCADE during Part 2 (dose expansion cohort) of the study. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib |
|---|---|
| Description | TEmax was determined to characterize the whole blood 20S proteasome inhibition parameters. |
| Time Frame | Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data is reported due to concerns about the third-party laboratory's performance of the 20S assay that precluded the ability to confirm the accuracy of the data generated. The data was not considered reliable. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR is defined as percentage of participants with complete response (CR) or partial response (PR) or minimal response (MR) as assessed by the investigator using International Myeloma Working Group Uniform Response criteria. CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg /24 h. MR=25-49% reduction in the serum monoclonal paraprotein maintained for a minimum of 6 weeks; 50-89% reduction in 24-h urinary light chain excretion, which still exceeds 200 mg/24 h, maintained for a minimum of 6 weeks; for participants with non-secretory myeloma only, 25-49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks; 25-49% reduction in the size of soft tissue plasmacytomas; no increase in the size or number of lytic bone lesions. |
| Time Frame | Cycle 1 through Cycle 115 (Up to 80.1 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and at least 1 post baseline disease assessment. |
| Arm/Group Title | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor. | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). |
| Measure Participants | 2 | 3 | 3 | 3 | 2 | 6 | 2 | 20 | 11 | 6 | 2 |
| CR+PR |
0
0%
|
0
0%
|
0
0%
|
33
1100%
|
0
0%
|
0
0%
|
50
1250%
|
5
25%
|
9
75%
|
33
550%
|
0
0%
|
| CR+PR+MR |
0
0%
|
0
0%
|
0
0%
|
33
1100%
|
0
0%
|
0
0%
|
50
1250%
|
10
50%
|
18
150%
|
33
550%
|
0
0%
|
Adverse Events
| Time Frame | From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | |||||||||||
| Arm/Group Description | Ixazomib 0.24 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days). | Ixazomib 0.48 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days). | Ixazomib 0.8 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days). | Ixazomib 1.2 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days). | Ixazomib 1.68 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days). | Ixazomib 2.23 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after >=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor (Up to 550 days). | Ixazomib 2.0 mg/m^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days). | |||||||||||
All Cause Mortality |
||||||||||||||||||||||
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
Serious Adverse Events |
||||||||||||||||||||||
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) | 2/3 (66.7%) | 0/3 (0%) | 5/7 (71.4%) | 3/4 (75%) | 14/20 (70%) | 6/12 (50%) | 3/6 (50%) | 2/2 (100%) | |||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||
| Thrombocytopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/7 (28.6%) | 1/4 (25%) | 3/20 (15%) | 1/12 (8.3%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Anaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hyperviscosity syndrome | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Febrile neutropenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Cardiac disorders | ||||||||||||||||||||||
| Cardiovascular disorder | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Arrhythmia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||
| Abdominal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Diarrhoea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gastritis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Nausea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Vomiting | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| General disorders | ||||||||||||||||||||||
| Pyrexia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 3/20 (15%) | 0/12 (0%) | 2/6 (33.3%) | 0/2 (0%) | |||||||||||
| Chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Non-cardiac chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Chills | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Infections and infestations | ||||||||||||||||||||||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 2/20 (10%) | 1/12 (8.3%) | 0/6 (0%) | 2/2 (100%) | |||||||||||
| Bacteraemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Sepsis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Septic shock | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Staphylococcal skin infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Urinary tract infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||
| Fall | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Compression fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Investigations | ||||||||||||||||||||||
| Fungal test positive | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Blood creatinine increased | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Troponin increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||
| Dehydration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/4 (25%) | 2/20 (10%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Hypercalcaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Hyperuricaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hypophosphataemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Fluid overload | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||
| Bone pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 2/20 (10%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Back pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pathological fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||
| Multiple myeloma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Plasmacytoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Malignant melanoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Nervous system disorders | ||||||||||||||||||||||
| Dizziness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Haemorrhage intracranial | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Headache | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Spinal cord compression | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Psychiatric disorders | ||||||||||||||||||||||
| Mental status changes | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||
| Renal failure acute | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Renal failure | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||
| Hypoxia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 2/20 (10%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Atelectasis | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pulmonary hypertension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||
| Rash | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Rash morbilliform | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Erythema multiforme | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Vascular disorders | ||||||||||||||||||||||
| Hypotension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Orthostatic hypotension | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 7/7 (100%) | 4/4 (100%) | 20/20 (100%) | 12/12 (100%) | 6/6 (100%) | 2/2 (100%) | |||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||
| Neutropenia | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/4 (0%) | 5/20 (25%) | 3/12 (25%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Lymphopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Leukopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 2/20 (10%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Anaemia | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 4/20 (20%) | 1/12 (8.3%) | 0/6 (0%) | 2/2 (100%) | |||||||||||
| Thrombocytopenia | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 3/7 (42.9%) | 3/4 (75%) | 9/20 (45%) | 3/12 (25%) | 3/6 (50%) | 2/2 (100%) | |||||||||||
| Pancytopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Cardiac disorders | ||||||||||||||||||||||
| Sinus tachycardia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 2/4 (50%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Cardiomegaly | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pericardial effusion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Tachycardia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Arrhythmia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||
| Cerumen impaction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Ear pain | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Eustachian tube obstruction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Tinnitus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Tympanic membrane perforation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Eye disorders | ||||||||||||||||||||||
| Vision blurred | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Ocular hyperaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Periorbital oedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Ocular discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Eye haemorrhage | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Eye irritation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Eye pruritus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Eyelid oedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Lacrimation increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Retinal detachment | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||
| Constipation | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 2/4 (50%) | 2/20 (10%) | 4/12 (33.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Abdominal discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 2/20 (10%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Abdominal pain upper | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Abdominal distension | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Aphthous ulcer | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Stomatitis | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Toothache | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dental discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dyspepsia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Flatulence | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gastrointestinal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gingival swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Haematochezia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Inguinal hernia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Lip swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Mouth cyst | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Mouth ulceration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Oral pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pancreatitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Rectal haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Nausea | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 4/7 (57.1%) | 3/4 (75%) | 7/20 (35%) | 8/12 (66.7%) | 5/6 (83.3%) | 1/2 (50%) | |||||||||||
| Diarrhoea | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/3 (0%) | 3/7 (42.9%) | 3/4 (75%) | 4/20 (20%) | 6/12 (50%) | 3/6 (50%) | 2/2 (100%) | |||||||||||
| Vomiting | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 2/7 (28.6%) | 4/4 (100%) | 5/20 (25%) | 4/12 (33.3%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||||
| Abdominal pain | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 2/4 (50%) | 0/20 (0%) | 2/12 (16.7%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Gastritis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gastrooesophageal reflux disease | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Tongue ulceration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| General disorders | ||||||||||||||||||||||
| Fatigue | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 2/3 (66.7%) | 4/7 (57.1%) | 2/4 (50%) | 12/20 (60%) | 8/12 (66.7%) | 2/6 (33.3%) | 2/2 (100%) | |||||||||||
| Asthenia | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 4/20 (20%) | 2/12 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Oedema peripheral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Application site erythema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Face oedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Feeling abnormal | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gait disturbance | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Malaise | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Mucosal dryness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Nodule | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pyrexia | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 1/7 (14.3%) | 3/4 (75%) | 6/20 (30%) | 5/12 (41.7%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||||
| Chills | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 3/4 (75%) | 3/20 (15%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Peripheral swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Influenza like illness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||
| Hyperbilirubinaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Immune system disorders | ||||||||||||||||||||||
| Seasonal allergy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Infections and infestations | ||||||||||||||||||||||
| Upper respiratory tract infection | 0/3 (0%) | 2/3 (66.7%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 4/7 (57.1%) | 1/4 (25%) | 6/20 (30%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Oral candidiasis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Pharyngitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Sinusitis | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Bronchitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Furuncle | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Herpes simplex | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Acute sinusitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Catheter site cellulitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Ear infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gastroenteritis viral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gastrointestinal viral infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Infected cyst | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Otitis media | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Parainfluenzae virus infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Post procedural cellulitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Staphylococcal bacteraemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Subcutaneous abscess | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Tooth abscess | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Conjunctivitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/7 (28.6%) | 0/4 (0%) | 3/20 (15%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Urinary tract infection | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 2/12 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Diarrhoea infectious | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Nasopharyngitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Streptococcal bacteraemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Bacteraemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Cellulitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Localised infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Rash pustular | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Staphylococcal infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||
| Contusion | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 2/20 (10%) | 2/12 (16.7%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Laceration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Post procedural oedema | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Arthropod bite | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Concussion | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Foot fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Infusion related reaction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Joint dislocation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Procedural pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Spinal compression fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Transfusion reaction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Fall | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Muscle strain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Skin abrasion | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Investigations | ||||||||||||||||||||||
| Weight decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| White blood cell count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Blood urea increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Neutrophil count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Blood calcium increased | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Electrocardiogram QT prolonged | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Haematocrit decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Haemoglobin decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Oxygen saturation decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Platelet count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Weight increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Blood testosterone decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Prostatic specific antigen increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Blood creatinine increased | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/4 (25%) | 2/20 (10%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||
| Decreased appetite | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 3/7 (42.9%) | 1/4 (25%) | 6/20 (30%) | 7/12 (58.3%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Hypokalaemia | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Hyponatraemia | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 3/20 (15%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hyperglycaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hyperkalaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hypermagnesaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hypoglycaemia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Increased appetite | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Vitamin B12 deficiency | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hypoalbuminaemia | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dehydration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 3/12 (25%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||||
| Hyperuricaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 2/20 (10%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hypophosphataemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hypercalcaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||
| Arthralgia | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 4/20 (20%) | 3/12 (25%) | 2/6 (33.3%) | 0/2 (0%) | |||||||||||
| Muscle spasms | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 2/7 (28.6%) | 0/4 (0%) | 3/20 (15%) | 3/12 (25%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Musculoskeletal chest pain | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 2/20 (10%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Muscular weakness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 2/2 (100%) | |||||||||||
| Musculoskeletal pain | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Myalgia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Joint swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Bursitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Neck pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pain in extremity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pain in jaw | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Back pain | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/7 (14.3%) | 1/4 (25%) | 3/20 (15%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Bone pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Joint stiffness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pathological fracture | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Soft tissue swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Spinal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||
| Bladder transitional cell carcinoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Melanocytic naevus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Basal cell carcinoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Squamous cell carcinoma of skin | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Nervous system disorders | ||||||||||||||||||||||
| Neuropathy peripheral | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 3/20 (15%) | 3/12 (25%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Hypoaesthesia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 2/6 (33.3%) | 0/2 (0%) | |||||||||||
| Paraesthesia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hyperaesthesia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 1/4 (25%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Somnolence | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Sinus headache | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 2/20 (10%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Balance disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Cranial nerve disorder | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Disturbance in attention | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hemiparesis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Peripheral sensory neuropathy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Syncope | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Tremor | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Headache | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 1/4 (25%) | 4/20 (20%) | 2/12 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Dizziness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/7 (28.6%) | 1/4 (25%) | 2/20 (10%) | 3/12 (25%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||||
| Psychiatric disorders | ||||||||||||||||||||||
| Confusional state | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Insomnia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Anxiety | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Mental status changes | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Depression | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Disorientation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Mood altered | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Restlessness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||
| Azotaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Dysuria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Haematuria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Micturition disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Nocturia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Urinary incontinence | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||
| Testicular pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Testicular swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Gynaecomastia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||
| Cough | 1/3 (33.3%) | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 2/3 (66.7%) | 2/7 (28.6%) | 0/4 (0%) | 8/20 (40%) | 3/12 (25%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Dyspnoea | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 1/7 (14.3%) | 1/4 (25%) | 4/20 (20%) | 1/12 (8.3%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Epistaxis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 2/12 (16.7%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Oropharyngeal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 2/20 (10%) | 3/12 (25%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dyspnoea exertional | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 3/12 (25%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Nasal congestion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Productive cough | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dysphonia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 2/20 (10%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pharyngeal inflammation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pleural effusion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pleuritic pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Sinus congestion | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Upper-airway cough syndrome | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Wheezing | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Sleep apnoea syndrome | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||
| Rash macular | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 2/7 (28.6%) | 2/4 (50%) | 4/20 (20%) | 2/12 (16.7%) | 3/6 (50%) | 1/2 (50%) | |||||||||||
| Rash pruritic | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 3/6 (50%) | 0/2 (0%) | |||||||||||
| Erythema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 2/20 (10%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Hyperhidrosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 2/4 (50%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pruritus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 2/4 (50%) | 1/20 (5%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Rash maculo-papular | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 2/4 (50%) | 0/20 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Rash papular | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 2/20 (10%) | 2/12 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dry skin | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Skin exfoliation | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 2/20 (10%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Swelling face | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Petechiae | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Rash erythematous | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Actinic keratosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Cold sweat | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dermal cyst | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dermatitis acneiform | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dermatitis allergic | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Dermatitis exfoliative | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Ecchymosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Photodermatosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Skin discolouration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Skin irritation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Skin lesion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Vasculitic rash | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Blister | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Papule | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Pseudofolliculitis barbae | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Rash | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 1/4 (25%) | 4/20 (20%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Skin hypopigmentation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||||
| Vascular disorders | ||||||||||||||||||||||
| Hypertension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/4 (0%) | 2/20 (10%) | 1/12 (8.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hot flush | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Haematoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/7 (0%) | 0/4 (0%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Hypotension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/7 (14.3%) | 0/4 (0%) | 1/20 (5%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||||
| Orthostatic hypotension | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 1/20 (5%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
| Aortic aneurysm | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/7 (0%) | 1/4 (25%) | 0/20 (0%) | 0/12 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||||
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 |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00932698
Other Study ID Numbers:
- C16003
- U1111-1177-7936
First Posted:
Jul 3, 2009
Last Update Posted:
Aug 7, 2019
Last Verified:
Jun 1, 2019