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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1206-2180 | Other Identifier | WHO |
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This is an open-label, multicenter, phase 1, dose escalation study of IXAZOMIB. The primary purpose of this study is to determine the safety profile, establish the maximum tolerated dose, and inform the phase 2 dose of IXAZOMIB administered intravenously in participants with nonhematologic malignancies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Ixazomib 0.125 milligram per square meter (mg/m^2) | Experimental | Ixazomib (MLN9708) 0.125 mg/m^2, injection, intravenously (IV), once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
|
| Part 1: Ixazomib 0.25 mg/m^2 | Experimental | Ixazomib (MLN9708) 0.25 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
|
| Part 1: Ixazomib 0.5 mg/m^2 | Experimental | Ixazomib (MLN9708) 0.5 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
|
| Part 1: Ixazomib 1 mg/m^2 | Experimental | Ixazomib (MLN9708) 1 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
|
| Part 1: Ixazomib 1.33 mg/m^2 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IXAZOMIB | Drug | All participants will receive IXAZOMIB IV injection on Days 1, 4, 8, and 11 of each treatment cycle followed by a rest period of 10 days. The first stage of the study will be initiated at a starting dose of 0.125 mg/m^2. Subsequent doses will increase until a maximum tolerated dose (MTD) is established. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Participants With Dose Limiting Toxicity (DLT) | Toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0. DLT is any of following related to ixazomib:Grade (GR) 4 neutropenia (absolute neutrophil count<500 cells/cubic meter[cells/mm^3])for>7 days; GR 3 neutropenia with coincident fever and/or infection; GR 4 thrombocytopenia (platelets <25,000 cells/mm3)for>7 days; GR 3 thrombocytopenia with clinically significant bleeding; Platelet count<10,000 cells/mm3; GR 3 peripheral neuropathy;>=GR 3 nausea/emesis in absence of optimal antiemetic therapy; >=GR 3 diarrhoea in absence of optimal supportive therapy;GR 3 QTc prolongation noted on average of 3 electrocardiograms (ECGs);>=GR 3 nonhematological toxicity except GR 3 arthralgia/myalgia or GR 3 fatigue for<1 week; Delay in initiation of subsequent therapy cycle by>7 days due to treatment-related toxicity Other>=GR 2 nonhematological toxicity that opinion of investigator, requires discontinuation of therapy with Ixazomib. | Part 1: Cycle 1 Day 1 up to Cycle 1 Day 21 |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs) | Part 1: Cycle 1 Day 1 up to Cycle 10 Day 41; Part 2: Cycle 1 Day 1 up to Cycle 12 Day 41 | |
| Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities | Day 1 up to 30 days after last dose of study drug (Cycle 12 Day 41) | |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital sign measurements included diastolic and systolic blood pressure, heart rate, weight and oral temperature. | Day 1 up to 30 days after last dose of study drug (Cycle 12 Day 41) |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for Ixazomib | AUC (0-72) is a measure of the area under the plasma concentration-time curve from time 0 to 72 hours post-dose for ixazomib. | Part 1: Cycle 1 Days 1 and 11: pre-dose and at multiple time points (up to 72 hours) post-dose |
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Inclusion Criteria:
Each participant must meet all of the following inclusion criteria to be enrolled in the study:
Male or female participants 18 years or older.
Eastern Cooperative Oncology Group performance status 0-2.
A diagnosis of a nonhematologic malignancy for which standard treatment is no longer effective. In the expanded cohort, enrollment will be limited to participants with a diagnosis of NSCLC, H&N cancer (squamous cell cancer), STS, or PC.
Suitable venous access for pharmacokinetic (PK) and pharmacodynamic evaluations.
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 2 effective methods of contraception or abstain from heterosexual intercourse.
Voluntary written consent must be obtained.
Adequate clinical laboratory values during the screening period.
In the escalation portion of the study, radiographically or clinically evaluable tumor was required, but measurable disease as defined by response evaluation criteria in solid tumors (RECIST) criteria was not required. In the MTD disease expansion cohorts and the TPEC, clinically measurable disease as defined by RECIST criteria was required for evaluation of NSCLC, H&N cancer, and STS. Prostate specific antigen (PSA) alone was acceptable for evaluation of PC.
For participants in the TPEC, tumor tissue that, in the opinion of the investigator, could have been safely biopsied using a core needle.
Exclusion Criteria:
Participants meeting any of the following exclusion criteria are not to be enrolled in the study:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States | ||
| Emory University |
Participants with diagnosis of nonhematologic malignancies were enrolled in 1 of the 2 parts, Part 1: Dose escalation to determine maximum tolerated dose (MTD), and Part 2: Expansion at MTD in 5 expansion cohorts.
Participants took part in the study at 7 investigative sites in the United States and Canada from 02 March 2009 to 20 April 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Ixazomib 0.125 mg/m^2 | Ixazomib (MLN9708) 0.125 milligram per square meter (mg/m^2), injection, intravenously (IV), once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| FG001 | Part 1: Ixazomib 0.25 mg/m^2 | Ixazomib (MLN9708) 0.25 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| FG002 | Part 1: Ixazomib 0.5 mg/m^2 | Ixazomib (MLN9708) 0.5 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| FG003 | Part 1: Ixazomib 1 mg/m^2 | Ixazomib (MLN9708) 1 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| FG004 | Part 1: Ixazomib 1.33 mg/m^2 | Ixazomib (MLN9708) 1.33 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| FG005 | Part 1: Ixazomib 1.76 mg/m^2 | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| FG006 | Part 1: Ixazomib 2.34 mg/m^2 | Ixazomib (MLN9708) 2.34 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| FG007 | Part 2:Ixazomib 1.76 mg/m^2-Non-small Cell Lung Cancer(NSCLC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with NSCLC during Part 2 of the study. |
| FG008 | Part 2: Ixazomib 1.76 mg/m^2-Head and Neck Cancer (H&N) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with H&N during Part 2 of the study. |
| FG009 | Part 2: Ixazomib 1.76 mg/m^2-Soft Tissue Sarcoma (STC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with STC during Part 2 of the study. |
| FG010 | Part 2: Ixazomib 1.76 mg/m^2-Prostate Cancer (PC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with PC during Part 2 of the study. |
| FG011 | Part 2: Ixazomib 1.76 mg/m^2-TPEC | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with various types of solid tumors suitable for biopsy in tumor pharmacodynamic expansion cohort (TPEC) during Part 2 of the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1: Part 1 |
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| ||||||||||||||||||
| Period 2: Part 2 |
|
The safety population included all participants who received at least 1 dose of ixazomib.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: Ixazomib 0.125 mg/m^2 | Ixazomib (MLN9708) 0.125 milligram per square meter (mg/m^2), injection, intravenously (IV), once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part 1: Number of Participants With Dose Limiting Toxicity (DLT) | Toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0. DLT is any of following related to ixazomib:Grade (GR) 4 neutropenia (absolute neutrophil count<500 cells/cubic meter[cells/mm^3])for>7 days; GR 3 neutropenia with coincident fever and/or infection; GR 4 thrombocytopenia (platelets <25,000 cells/mm3)for>7 days; GR 3 thrombocytopenia with clinically significant bleeding; Platelet count<10,000 cells/mm3; GR 3 peripheral neuropathy;>=GR 3 nausea/emesis in absence of optimal antiemetic therapy; >=GR 3 diarrhoea in absence of optimal supportive therapy;GR 3 QTc prolongation noted on average of 3 electrocardiograms (ECGs);>=GR 3 nonhematological toxicity except GR 3 arthralgia/myalgia or GR 3 fatigue for<1 week; Delay in initiation of subsequent therapy cycle by>7 days due to treatment-related toxicity Other>=GR 2 nonhematological toxicity that opinion of investigator, requires discontinuation of therapy with Ixazomib. | The DLT population included all participants who received all Cycle 1 doses of ixazomib and who had completed Cycle 1. If Cycle 1 was interrupted by a DLT, the participant was included in this population. | Posted | Number | participants | Part 1: Cycle 1 Day 1 up to Cycle 1 Day 21 |
Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to Part 1: Cycle 10 Day 41, Part 2: Cycle 12 Day 41)
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: Ixazomib 0.125 mg/m^2 | Ixazomib (MLN9708) 0.125 milligram per square meter (mg/m^2), injection, intravenously (IV), once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| ID | Term |
|---|---|
| C548400 | ixazomib |
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| Experimental |
Ixazomib (MLN9708) 1.33 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
|
| Part 1: Ixazomib 1.76 mg/m^2 | Experimental | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
|
| Part 1: Ixazomib 2.34 mg/m^2 | Experimental | Ixazomib (MLN9708) 2.34 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. Once the MTD will be established, participants with NSCLC, Head and Neck Cancer (H&N), Soft Tissue Sarcoma (STC) or Prostate Cancer (PC) will be included in MTD disease expanded cohort. An additional tumor pharmacodynamics expansion cohort (TPEC) will enroll participants with any type of solid tumor that can be biopsied for tissue analysis before and after treatment with ixazomib. |
|
| Part 2:Ixazomib 1.76 mg/m^2-NSCLC | Experimental | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with NSCLC during Part 2 of the study. |
|
| Part 2: Ixazomib 1.76 mg/m^2-H&N | Experimental | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with H&N during Part 2 of the study. |
|
| Part 2: Ixazomib 1.76 mg/m^2-STC | Experimental | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with STC during Part 2 of the study. |
|
| Part 2: Ixazomib 1.76 mg/m^2-PC | Experimental | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with PC during Part 2 of the study. |
|
| Part 2: Ixazomib 1.76 mg/m^2-TPEC | Experimental | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with various types of solid tumors suitable for biopsy in tumor pharmacodynamic expansion cohort (TPEC) during Part 2 of the study. |
|
|
| Part 1: C0: Initial Plasma Concentration After Bolus Intravenous Administration |
C0 is the plasma drug concentration at time zero following bolus intravenous injection. |
| Part 1: Cycle 1 Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose |
| Part 1: Rac: Accumulation Ratio for Ixazomib | Rac was estimated as the ratio of AUC (0-72) on Day 11 and AUC (0-72) on Day 1. AUC (0-72) is the area under the plasma concentration-time curve from time 0 to 72 hours post-dose. | Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Part 1: Terminal Phase Elimination Half-life (T1/2) for Ixazomib | T1/2 is the time required for half of the drug to be eliminated from the plasma. | Part 1: Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose |
| Part 1: E Max: Maximum Observed Effect for Ixazomib | E max is the maximum inhibition of 20S proteasome activity in whole blood. | Part 1: Cycle 1 Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose |
| Part 1: TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib | TEmax is the time to reach the Emax, equal to time (hours) to Emax. | Part 1: Cycle 1 Days 1 and 11 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose |
| Number of Participants With Best Overall Response | Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria. Complete Response (CR): disappearance of all target lesions, non-target lesions and normalization of tumor marker level. Partial Response (PR): at least 30% decrease in sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the baseline smallest sum of longest diameter; persistence of 1 or more non-target lesion(s) or maintenance of tumor marker level above normal limits. Progressive disease: at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the baseline smallest sum of longest diameter or appearance of 1 or more new lesions or unequivocal progression of existing non-target lesions. | Day 18 up to Day 21 of each cycle (Part 1: up to Cycle 10; Part 2: up to Cycle 12) |
| Part 2: Ixazomib Concentration in Postdose Clinical Tumor Samples in Ixazomib 1.76 mg/m^2-TPEC | The average data of Days 1 and 4 of Cycle 1 was reported. | Cycle 1 Days 1 and 4: Predose and (from 4-20 hours) post-dose |
| 20S Proteasome Activity of Ixazomib in the Tumor Tissue | Cycle 1 Days 1 and 4 pre-dose and at multiple time points (up to 2 hours of tumor biopsy) post-dose |
| Expression of Biomarker (ATF-3) in Tumor Tissue | Cycle 1 Days 1 and 4 pre-dose and at multiple time points (up to 2 hours of tumor biopsy) post-dose |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Duke University | Durham | North Carolina | 27710 | United States |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| University of Washington- Seattle Cancer Care | Seattle | Washington | 98109 | United States |
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| Withdrawal by Subject |
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| Adverse Event |
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| Progressive disease |
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| COMPLETED |
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| NOT COMPLETED |
|
|
| Part 1: Ixazomib 0.25 mg/m^2 |
Ixazomib (MLN9708) 0.25 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| BG002 | Part 1: Ixazomib 0.5 mg/m^2 | Ixazomib (MLN9708) 0.5 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| BG003 | Part 1: Ixazomib 1 mg/m^2 | Ixazomib (MLN9708) 1 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| BG004 | Part 1: Ixazomib 1.33 mg/m^2 | Ixazomib (MLN9708) 1.33 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| BG005 | Part 1: Ixazomib 1.76 mg/m^2 | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| BG006 | Part 1: Ixazomib 2.34 mg/m^2 | Ixazomib (MLN9708) 2.34 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. |
| BG007 | Part 2:Ixazomib 1.76 mg/m^2-Non-small Cell Lung Cancer(NSCLC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with NSCLC during Part 2 of the study. |
| BG008 | Part 2: Ixazomib 1.76 mg/m^2-Head and Neck Cancer (H&N) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with H&N during Part 2 of the study. |
| BG009 | Part 2: Ixazomib 1.76 mg/m^2-Soft Tissue Sarcoma (STC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with STC during Part 2 of the study. |
| BG010 | Part 2: Ixazomib 1.76 mg/m^2-Prostate Cancer (PC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with PC during Part 2 of the study. |
| BG011 | Part 2: Ixazomib 1.76 mg/m^2-TPEC | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with various types of solid tumors suitable for biopsy in tumor pharmacodynamic expansion cohort (TPEC) during Part 2 of the study. |
| BG012 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
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| Weight | Mean | Standard Deviation | kilogram (kg) |
|
| Body surface area | Mean | Standard Deviation | square meter (m^2) |
|
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| Primary | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs) | The safety population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Part 1: Cycle 1 Day 1 up to Cycle 10 Day 41; Part 2: Cycle 1 Day 1 up to Cycle 12 Day 41 |
|
|
|
| Primary | Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities | The safety population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Day 1 up to 30 days after last dose of study drug (Cycle 12 Day 41) |
|
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| Primary | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital sign measurements included diastolic and systolic blood pressure, heart rate, weight and oral temperature. | The safety population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Day 1 up to 30 days after last dose of study drug (Cycle 12 Day 41) |
|
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| Secondary | Part 1: AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for Ixazomib | AUC (0-72) is a measure of the area under the plasma concentration-time curve from time 0 to 72 hours post-dose for ixazomib. | PK analysis population where data at specified time points was available,defined as participants in dose escalation phase who received protocol-specified dosing in Cycle 1 without dose reductions/interruptions, did not receive excluded concomitant medications in Cycle 1,had sufficient concentration-time data to permit estimation of PK parameters. | Posted | Geometric Mean | Standard Deviation | nanogram*hour per milliliter (ng*hr/mL) | Part 1: Cycle 1 Days 1 and 11: pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Secondary | Part 1: C0: Initial Plasma Concentration After Bolus Intravenous Administration | C0 is the plasma drug concentration at time zero following bolus intravenous injection. | PK analysis population where data at specified time points was available, defined as participants in dose escalation phase who received protocol-specified dosing in Cycle 1 without dose reductions/interruptions,did not receive excluded concomitant medications in Cycle 1,had sufficient concentration-time data to permit estimation of PK parameters. | Posted | Geometric Mean | Standard Deviation | nanogram per mililiter (ng/mL) | Part 1: Cycle 1 Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose |
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|
|
| Secondary | Part 1: Rac: Accumulation Ratio for Ixazomib | Rac was estimated as the ratio of AUC (0-72) on Day 11 and AUC (0-72) on Day 1. AUC (0-72) is the area under the plasma concentration-time curve from time 0 to 72 hours post-dose. | PK analysis population defined as participants in dose escalation phase who received protocol-specified dosing in Cycle 1 without dose reductions/interruptions,did not receive excluded concomitant medications in Cycle 1,had sufficient concentration-time data to permit estimation of PK parameters. | Posted | Geometric Mean | Standard Deviation | ratio | Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose |
|
|
|
| Secondary | Part 1: Terminal Phase Elimination Half-life (T1/2) for Ixazomib | T1/2 is the time required for half of the drug to be eliminated from the plasma. | PK analysis population defined as participants in dose escalation phase who received protocol-specified dosing in Cycle 1 without dose reductions/interruptions,did not receive excluded concomitant medications in Cycle 1,had sufficient concentration-time data to permit estimation of PK parameters. | Posted | Geometric Mean | Standard Deviation | hours | Part 1: Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose |
|
|
|
| Secondary | Part 1: E Max: Maximum Observed Effect for Ixazomib | E max is the maximum inhibition of 20S proteasome activity in whole blood. | PD analysis population where baseline/post-baseline assessments was available, defined as participants in dose escalation phase who received protocol-specified dosing in Cycle 1 without dose reductions/interruptions,did not receive any excluded concomitant medications in Cycle 1,had sufficient effect-time data to permit estimation of PD parameters. | Posted | Mean | Standard Deviation | percentage of inhibition | Part 1: Cycle 1 Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose |
|
|
|
| Secondary | Part 1: TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib | TEmax is the time to reach the Emax, equal to time (hours) to Emax. | PD analysis population where baseline/post-baseline assessments was available, defined as participants in dose escalation phase who received protocol-specified dosing in Cycle 1 without dose reductions/interruptions,did not receive any excluded concomitant medications in Cycle 1,had sufficient effect-time data to permit estimation of PD parameters. | Posted | Median | Full Range | hour | Part 1: Cycle 1 Days 1 and 11 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose |
|
|
|
| Secondary | Number of Participants With Best Overall Response | Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria. Complete Response (CR): disappearance of all target lesions, non-target lesions and normalization of tumor marker level. Partial Response (PR): at least 30% decrease in sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the baseline smallest sum of longest diameter; persistence of 1 or more non-target lesion(s) or maintenance of tumor marker level above normal limits. Progressive disease: at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the baseline smallest sum of longest diameter or appearance of 1 or more new lesions or unequivocal progression of existing non-target lesions. | The response-evaluable population included all participants who received at least 1 cycle of ixazomib treatment, had measurable disease at baseline, and had at least 1 postbaseline response assessment. | Posted | Number | participants | Day 18 up to Day 21 of each cycle (Part 1: up to Cycle 10; Part 2: up to Cycle 12) |
|
|
|
| Secondary | Part 2: Ixazomib Concentration in Postdose Clinical Tumor Samples in Ixazomib 1.76 mg/m^2-TPEC | The average data of Days 1 and 4 of Cycle 1 was reported. | The tumor PK analysis set where Day 1 and 4 assessment were available. The tumor PK and PD analysis population includes all participants who provided a baseline tumor biopsy sample and 1 post-baseline tumor biopsy sample on Day 1 or Day 4. | Posted | Mean | Standard Deviation | nanogram per gram (ng/g) | Cycle 1 Days 1 and 4: Predose and (from 4-20 hours) post-dose |
|
|
|
| Secondary | 20S Proteasome Activity of Ixazomib in the Tumor Tissue | This outcome measure was not analyzed due to lack of tumor activity data. | Posted | Cycle 1 Days 1 and 4 pre-dose and at multiple time points (up to 2 hours of tumor biopsy) post-dose |
|
|
| Secondary | Expression of Biomarker (ATF-3) in Tumor Tissue | This outcome measure was not analyzed due to lack of tumor activity data. | Posted | Cycle 1 Days 1 and 4 pre-dose and at multiple time points (up to 2 hours of tumor biopsy) post-dose |
|
|
| 0 |
| 1 |
| 1 |
| 1 |
| 1 |
| 1 |
| EG001 | Part 1: Ixazomib 0.25 mg/m^2 | Ixazomib (MLN9708) 0.25 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. | 0 | 1 | 1 | 1 | 1 | 1 |
| EG002 | Part 1: Ixazomib 0.5 mg/m^2 | Ixazomib (MLN9708) 0.5 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG003 | Part 1: Ixazomib 1 mg/m^2 | Ixazomib (MLN9708) 1 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. | 1 | 7 | 1 | 7 | 7 | 7 |
| EG004 | Part 1: Ixazomib 1.33 mg/m^2 | Ixazomib (MLN9708) 1.33 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. | 1 | 4 | 1 | 4 | 4 | 4 |
| EG005 | Part 1: Ixazomib 1.76 mg/m^2 | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. | 0 | 6 | 4 | 6 | 6 | 6 |
| EG006 | Part 1: Ixazomib 2.34 mg/m^2 | Ixazomib (MLN9708) 2.34 mg/m^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. | 1 | 3 | 3 | 3 | 3 | 3 |
| EG007 | Part 2:Ixazomib 1.76 mg/m^2-Non-small Cell Lung Cancer(NSCLC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with NSCLC during Part 2 of the study. | 0 | 20 | 9 | 20 | 20 | 20 |
| EG008 | Part 2: Ixazomib 1.76 mg/m^2-Head and Neck Cancer (H&N) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with H&N during Part 2 of the study. | 2 | 22 | 10 | 22 | 22 | 22 |
| EG009 | Part 2: Ixazomib 1.76 mg/m^2-Soft Tissue Sarcoma (STC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with STC during Part 2 of the study. | 1 | 20 | 7 | 20 | 20 | 20 |
| EG010 | Part 2: Ixazomib 1.76 mg/m^2-Prostate Cancer (PC) | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with PC during Part 2 of the study. | 0 | 11 | 6 | 11 | 11 | 11 |
| EG011 | Part 2: Ixazomib 1.76 mg/m^2-TPEC | Ixazomib (MLN9708) 1.76 mg/m^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with various types of solid tumors suitable for biopsy in tumor pharmacodynamic expansion cohort (TPEC) during Part 2 of the study. | 1 | 20 | 11 | 20 | 20 | 20 |
| Bronchitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Metabolic acidosis | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Cardiac failure congestive | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
|
| Cardiac failure acute | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
|
| Diastolic dysfunction | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
|
| Malignant haemangiopericytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
|
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
|
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
|
| Thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Scrotal oedema | Reproductive system and breast disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Retching | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Anorectal discomfort | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lip blister | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lip disorder | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lip swelling | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Swollen tongue | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Tooth loss | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Erythema nodosum | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Horner's syndrome | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypertonia | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Phantom pain | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Visual field defect | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Paranasal sinus hypersecretion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Respiratory depth decreased | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rhonchi | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Early satiety | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Facial pain | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Localised oedema | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Infusion site pain | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Nodule | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood magnesium decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood uric acid decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Blood urine present | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (15.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Body tinea | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| H1N1 influenza | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Localised infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Conjunctival oedema | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Disorder of orbit | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Eye disorder | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Face injury | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Incision site pain | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Nail injury | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
|
| Cor pulmonale | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Urinary hesitation | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (15.0) | Systematic Assessment |
|
| Auricular perichondritis | Ear and labyrinth disorders | MedDRA (15.0) | Systematic Assessment |
|
| Auricular swelling | Ear and labyrinth disorders | MedDRA (15.0) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (15.0) | Systematic Assessment |
|
| Tympanic membrane perforation | Ear and labyrinth disorders | MedDRA (15.0) | Systematic Assessment |
|
| Food allergy | Immune system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pelvic discomfort | Reproductive system and breast disorders | MedDRA (15.0) | Systematic Assessment |
|
| Testicular pain | Reproductive system and breast disorders | MedDRA (15.0) | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (15.0) | Systematic Assessment |
|
| Metastatic pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (15.0) | Systematic Assessment |
|
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
| SAEs |
|
| Renal function analyses |
|
| Tissue enzyme analyses notelsewhereclassified(NEC) |
|
| Red blood cell analyses |
|
| Platelet analyses |
|
| Mineral and electrolyte analyses |
|
| Metabolism tests NEC |
|
| Urinalysis NEC |
|
| White blood cell analyses |
|
| Thrombocytopenias |
|
| Anaemias NEC |
|
| Leukopenias NEC |
|
| Neutropenias |
|
| Leukocytoses NEC |
|
| Marrow depression and hypoplastic anaemias |
|
| Thrombocytoses |
|
| Sodium imbalance |
|
| Hyperglycaemic conditions NEC |
|
| Potassium imbalance |
|
| Calcium metabolism disorders |
|
| Magnesium metabolism disorders |
|
| Disorders of purine metabolism |
|
| Metabolic acidoses (excluding diabetic acidoses) |
|
| Phosphorus metabolism disorders |
|
| Protein metabolism disorders NEC |
|
| Coagulation and bleeding analyses |
|
|
| Cycle 1 Day 11 |
|
|
|
| Cycle 1 Day 11 |
|
|
|
| Cycle 1 Day 11 |
|
|
|
| Cycle 1 Day 11 |
|
|
| PR |
|
| SD |
|
| Progressive disease |
|