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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1166-8981 | Registry Identifier | WHO (UTN) |
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This study is an open-label, multicenter, phase 1, dose-escalation study of IXAZOMIB in adult patients with lymphoma. This study will be the first to administer IXAZOMIB to patients with lymphoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IXAZOMIB | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IXAZOMIB | Drug | Patients will be administered IXAZOMIB by IV on Days 1, 8, and 15 of a 28-day cycle. The first stage of the study will be initiated at a starting dose of 0.125 mg/m2. Subsequent doses will increase until a maximum tolerated dose (MTD) is established. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. | Baseline up to 30 days after last dose of study drug |
| Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Hematology, clinical chemistry and urinalysis were performed. TEAEs related to laboratory assessment observed at any time-points were reported under 3 system organ classes: blood and lymphatic system disorders, metabolism and nutrition disorders, and investigations. | Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45) |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital signs included body temperature, weight, systolic and diastolic blood pressure and heart rate. | Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles |
| Maximum Tolerated Dose (MTD) | The MTD was defined as the highest dose of ixazomib that generated dose limiting toxicity (DLT) during Cycle 1 in 0 of 3 or 1 of 6 participants. DLT defined as any of the following considered possibly related to therapy by investigator: 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 for >7 days; platelet count <25,000 cells/mm^3; 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 maximal supportive therapy; Grade 3 QTc prolongation>500 millisecond (msec);any >=Grade 3 nonhematologic toxicity except arthralgia/myalgia; <1 week fatigue; delay in the initiation of the subsequent therapy cycle by >=7 days ; other Grade 2 ixazomib-related nonhematologic toxicities requiring therapy discontinuation. |
| Measure | Description | Time Frame |
|---|---|---|
| C0: Initial Plasma Concentration After Bolus Intravenous Administration | C0 is the plasma drug concentration at time zero following bolus intravenous injection, obtained from the plasma concentration-time curve. | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose) |
| AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib |
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Inclusion Criteria:
Male or female patients 18 years or older.
Eastern Cooperative Oncology Group performance status 0-2.
Patients must have a confirmed diagnosis of lymphoma that is relapsed and/or refractory after at least 2 prior chemotherapeutic regimens and for which no curative option exists. Patients with Waldenstrom's macroglobulinemia are not eligible for enrollment in this study. Patients with Hodgkin lymphoma are considered eligible for this study.
Suitable venous access for PK and pharmacodynamic evaluations.
Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
Male patients who agree to to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
Voluntary written consent must be obtained.
Adequate blood and chemistry values during the screening period:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tower Cancer Research Center | Beverly Hills | California | 90211 | United States | ||
| Rocky Mountain Cancer Center |
Participants with historical diagnosis of lymphoma, for whom at least 2 previous chemotherapeutic regimens failed and no curative option existed enrolled in 1 of 8 treatment groups based on ixazomib's dose: 0.125 milligram per square meter (mg/m^2), 0.25 mg/m^2, 0.5 mg/m^2, 1 mg/m^2, 1.4 mg/m^2, 1.76 mg/m^2, 2.34 mg/m^2, 3.11 mg/m^2.
Participants took part in the study at 7 investigative sites in the United States and Canada from 20 August 2009 to 23 October 2014. Out of a total of 31 participants who were enrolled, 30 participants received at least 1 dose of ixazomib.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ixazomib 0.125 mg/m^2 | Ixazomib (MLN9708) 0.125 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until progressive disease (PD) or unacceptable toxicity. |
| FG001 | Ixazomib 0.25 mg/m^2 | Ixazomib (MLN9708) 0.25 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| FG002 | Ixazomib 0.5 mg/m^2 | Ixazomib (MLN9708) 0.5 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| FG003 | Ixazomib 1.0 mg/m^2 | Ixazomib (MLN9708) 1.0 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| FG004 | Ixazomib 1.4 mg/m^2 | Ixazomib (MLN9708) 1.4 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| FG005 | Ixazomib 1.76 mg/m^2 | Ixazomib (MLN9708) 1.76 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| FG006 | Ixazomib 2.34 mg/m^2 | Ixazomib (MLN9708) 2.34 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| FG007 | Ixazomib 3.11 mg/m^2 | Ixazomib (MLN9708) 3.11 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population included all participants who received at least 1 dose of ixazomib.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ixazomib 0.125 mg/m^2 | Ixazomib (MLN9708) 0.125 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| BG001 | Ixazomib 0.25 mg/m^2 |
| 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 | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. | Safety population included all participants who received at least 1 dose of ixazomib. | Posted | Number | participants | Baseline up to 30 days after last dose of study drug |
Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug. All AEs/SAEs were reported after administration of the first dose of the study drug and through 30 days after the last dose of study drug.
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 | Ixazomib 0.125 mg/m^2 | Ixazomib (MLN9708) 0.125 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Wound infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA (16.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | clinicaltrialregistry@tpna.com |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| C548400 | ixazomib |
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| Treatment Cycle 1 |
| Recommended Phase 2 Dose (RP2D) | The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond. | Baseline up to Treatment Cycle 45 |
AUC(0-168) is a measure of the area under the plasma concentration time-curve from time 0 to 168 hours postdose |
| Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) |
| Terminal Phase Elimination Half-life (T1/2) for Ixazomib | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose) |
| Rac: Accumulation Ratio for Ixazomib | Rac was estimated as the ratio of AUC (0-168) on Day 15 and AUC (0-168) on Day 1. AUC (0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose. | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) |
| Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose | Ae (0-4) is the total amount of drug excreted in the urine from 0 to 4 hours postdose. | Cycle 1, Days 1 and 15: 0 to 4 hours postdose |
| Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose | Fe (0-4) is the fraction of the dose excreted unchanged in the urine from 0 to 4 hours postdose, calculated as percentage of the exact dose administered. | Cycle 1, Days 1 and 15: 0 to 4 hours postdose |
| CLr: Renal Clearance | CLr is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time, calculated as the amount of drug excreted in the urine divided by the area under the plasma concentration-time curve, expressed in liter per hour (L/hr). | Cycle 1, Days 1 and 15: 0 to 4 hours postdose |
| Emax: Maximum Observed Effect for Ixazomib | Emax is the maximum inhibition of 20S proteasome activity in whole blood. | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) |
| TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib | TEmax: Time to reach the maximum observed effect (Emax), equal to time (hours) to Emax. | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) |
| Overall Best Response | Overall best response is the best response observed for a participant during the study based on International Working Group (IWG) Response Criteria for malignant lymphoma. Complete response (CR) as per IWG is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response (PR) is a minimum of 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes. Stable disease (SD) is when a participant fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD. PD is any new lesion or increase by >50% of previously involved sites from nadir. | Baseline up to Cycle 45 |
| Denver |
| Colorado |
| 80218 |
| United States |
| Kansas University Medical Center | Westwood | Kansas | 66160 | United States |
| Cornell University | New York | New York | 10021 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| University of Wisconsin Madison | Madison | Wisconsin | 53792 | United States |
| Jewish General Hospital | Montreal | Quebec | H3T 1E2 | Canada |
Ixazomib (MLN9708) 0.25 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.
| BG002 | Ixazomib 0.5 mg/m^2 | Ixazomib (MLN9708) 0.5 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| BG003 | Ixazomib 1.0 mg/m^2 | Ixazomib (MLN9708) 1.0 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| BG004 | Ixazomib 1.4 mg/m^2 | Ixazomib (MLN9708)1.4 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| BG005 | Ixazomib 1.76 mg/m^2 | Ixazomib (MLN9708) 1.76 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| BG006 | Ixazomib 2.34 mg/m^2 | Ixazomib (MLN9708) 2.34 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| BG007 | Ixazomib 3.11 mg/m^2 | Ixazomib (MLN9708) 3.11 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| BG008 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Body surface area (BSA) | Mean | Standard Deviation | square meter |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
|
| Weight | Mean | Standard Deviation | kilogram (kg) |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status | ECOG performance status is used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead. | Number | participants |
|
| Ann Arbor Stage | Ann Arbor staging is staging system for lymphomas. The stage is determined by location of tumor. Stage I (located in a single region, usually 1 lymph node and surrounding area), Stage II (located in 2 separate regions, an affected lymph node or organ and a second affected area, and both affected areas are confined to 1 side of diaphragm), Stage III (spread to both sides of diaphragm, including organ/area near lymph nodes/spleen), Stage IV (diffuse or disseminated involvement of 1 or more extra lymphatic organs, including any involvement of liver, bone marrow or nodular involvement of lungs). | Number | participants |
|
| Disease Histological Class | For this outcome measure, number of participants evaluable were 1, 1, 1, 1, 4, 7, 9 and 4 for each arm, respectively. | Number | participants |
|
| Time Since Primary Diagnosis to First Dose | Mean | Standard Deviation | months |
|
| ID | Title | Description |
|---|
| OG000 | Ixazomib 0.125 mg/m^2 | Ixazomib (MLN9708) 0.125 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| OG001 | Ixazomib 0.25 mg/m^2 | Ixazomib (MLN9708) 0.25 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| OG002 | Ixazomib 0.5 mg/m^2 | Ixazomib (MLN9708) 0.5 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| OG003 | Ixazomib 1.0 mg/m^2 | Ixazomib (MLN9708) 1.0 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| OG004 | Ixazomib 1.4 mg/m^2 | Ixazomib (MLN9708)1.4 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| OG005 | Ixazomib1.76 mg/m^2 | Ixazomib (MLN9708) 1.76 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| OG006 | Ixazomib 2.34 mg/m^2 | Ixazomib (MLN9708) 2.34 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
| OG007 | Ixazomib 3.11 mg/m² | Ixazomib (MLN9708) 3.11 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. |
|
|
| Primary | Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Hematology, clinical chemistry and urinalysis were performed. TEAEs related to laboratory assessment observed at any time-points were reported under 3 system organ classes: blood and lymphatic system disorders, metabolism and nutrition disorders, and investigations. | Safety population included all participants who received at least 1 dose of ixazomib. | Posted | Number | participants | Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45) |
|
|
|
| Primary | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital signs included body temperature, weight, systolic and diastolic blood pressure and heart rate. | Safety population included all participants who received at least 1 dose of ixazomib. | Posted | Number | participants | Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles |
|
|
|
| Primary | Maximum Tolerated Dose (MTD) | The MTD was defined as the highest dose of ixazomib that generated dose limiting toxicity (DLT) during Cycle 1 in 0 of 3 or 1 of 6 participants. DLT defined as any of the following considered possibly related to therapy by investigator: 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 for >7 days; platelet count <25,000 cells/mm^3; 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 maximal supportive therapy; Grade 3 QTc prolongation>500 millisecond (msec);any >=Grade 3 nonhematologic toxicity except arthralgia/myalgia; <1 week fatigue; delay in the initiation of the subsequent therapy cycle by >=7 days ; other Grade 2 ixazomib-related nonhematologic toxicities requiring therapy discontinuation. | DLT-Evaluable Population included participants who received all Cycle 1 doses of MLN9708 and who completed Cycle 1. If Cycle 1 was interrupted by a DLT, the participant was included in this population. | Posted | Number | mg/m^2 | Treatment Cycle 1 |
|
|
|
| Primary | Recommended Phase 2 Dose (RP2D) | The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond. | Safety population included all participants who received at least 1 dose of ixazomib. | Posted | Number | mg/m^2 | Baseline up to Treatment Cycle 45 |
|
|
|
| Secondary | C0: Initial Plasma Concentration After Bolus Intravenous Administration | C0 is the plasma drug concentration at time zero following bolus intravenous injection, obtained from the plasma concentration-time curve. | The pharmacokinetic (PK) analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters where Days 1 and 15 assessments were available. | Posted | Geometric Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose) |
|
|
|
| Secondary | AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib | AUC(0-168) is a measure of the area under the plasma concentration time-curve from time 0 to 168 hours postdose | The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters where Days 1 and 15 assessments were available. AUC(0-168) is not reported for ixazomib 0.125 and 0.25 mg/m^2 as the participants were not evaluable for this parameter. | Posted | Geometric Mean | Standard Deviation | hour*nanogram per milliliter (hr*ng/mL) | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) |
|
|
|
| Secondary | Terminal Phase Elimination Half-life (T1/2) for Ixazomib | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters.T1/2 is not reported for ixazomib 0.125 and 0.25 mg/m^2 as the participants were not evaluable for this parameter. | Posted | Geometric Mean | Standard Deviation | hr | Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose) |
|
|
|
| Secondary | Rac: Accumulation Ratio for Ixazomib | Rac was estimated as the ratio of AUC (0-168) on Day 15 and AUC (0-168) on Day 1. AUC (0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose. | The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters. Rac is reported for ixazomib 1.4, 2.34 and 3.11 mg/m^2 groups only as it could not be estimated for the other dosing groups. | Posted | Geometric Mean | Standard Deviation | ratio | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) |
|
|
|
| Secondary | Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose | Ae (0-4) is the total amount of drug excreted in the urine from 0 to 4 hours postdose. | The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters where Days 1 and 15 assessments were available. | Posted | Geometric Mean | Standard Deviation | nanogram | Cycle 1, Days 1 and 15: 0 to 4 hours postdose |
|
|
|
| Secondary | Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose | Fe (0-4) is the fraction of the dose excreted unchanged in the urine from 0 to 4 hours postdose, calculated as percentage of the exact dose administered. | The PK analysis population was defined as participants who had sufficient dosing data and ixazomib concentration-time data to permit the calculation of PK parameters where Days 1 and 15 assessments were available. | Posted | Geometric Mean | Standard Deviation | percentage of dose | Cycle 1, Days 1 and 15: 0 to 4 hours postdose |
|
|
|
| Secondary | CLr: Renal Clearance | CLr is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time, calculated as the amount of drug excreted in the urine divided by the area under the plasma concentration-time curve, expressed in liter per hour (L/hr). | The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters where Days 1 and 15 assessments were available. CLr is not reported for ixazomib 0.125 and 0.25 mg/m^2 as the participants were not evaluable for this parameter. | Posted | Geometric Mean | Standard Deviation | L/hr | Cycle 1, Days 1 and 15: 0 to 4 hours postdose |
|
|
|
| Secondary | Emax: Maximum Observed Effect for Ixazomib | Emax is the maximum inhibition of 20S proteasome activity in whole blood. | The pharmacodynamic analysis population included participants who had sufficient dosing data and effect-time data to permit calculation of pharmacodynamic parameters where Days 1 and 15 assessments were available. | Posted | Mean | Standard Deviation | percentage of inhibition | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) |
|
|
|
| Secondary | TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib | TEmax: Time to reach the maximum observed effect (Emax), equal to time (hours) to Emax. | The pharmacodynamic analysis population included participants who had sufficient dosing data and effect-time data to permit calculation of pharmacodynamic parameters where Days 1 and 15 assessments were available. | Posted | Median | Full Range | hr | Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) |
|
|
|
| Secondary | Overall Best Response | Overall best response is the best response observed for a participant during the study based on International Working Group (IWG) Response Criteria for malignant lymphoma. Complete response (CR) as per IWG is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response (PR) is a minimum of 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes. Stable disease (SD) is when a participant fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD. PD is any new lesion or increase by >50% of previously involved sites from nadir. | Response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and at least 1 postbaseline disease assessment for analyses of response. | Posted | Number | participants | Baseline up to Cycle 45 |
|
|
|
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | Ixazomib 0.25 mg/m^2 | Ixazomib (MLN9708) 0.25 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. | 0 | 1 | 1 | 1 |
| EG002 | Ixazomib 0.5 mg/m^2 | Ixazomib (MLN9708) 0.5 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. | 0 | 1 | 1 | 1 |
| EG003 | Ixazomib 1.0 mg/m^2 | Ixazomib (MLN9708) 1.0 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. | 0 | 1 | 1 | 1 |
| EG004 | Ixazomib 1.4 mg/m^2 | Ixazomib (MLN9708)1.4 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. | 2 | 4 | 4 | 4 |
| EG005 | Ixazomib 1.76 mg/m^2 | Ixazomib (MLN9708) 1.76 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. | 1 | 7 | 7 | 7 |
| EG006 | Ixazomib 2.34 mg/m^2 | Ixazomib (MLN9708) 2.34 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. | 4 | 10 | 10 | 10 |
| EG007 | Ixazomib 3.11 mg/m^2 | Ixazomib (MLN9708) 3.11 mg/m^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity. | 3 | 5 | 5 | 5 |
| Influenza | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Colorectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Mantle cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Mass | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Faeces pale | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Oesophageal disorder | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Neck mass | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Allergic respiratory symptom | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Painful respiration | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypouricaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Exfoliative rash | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Skin fibrosis | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Skin induration | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Computerised tomogram abnormal | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Vitamin D decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Furuncle | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Erythema of eyelid | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eye disorder | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eye swelling | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Depressive symptom | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Jugular vein thrombosis | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (16.0) | 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.
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| Metabolism and nutrition disorders |
|
| Investigations |
|
| Day 15 (n= 0, 0, 1, 1, 4, 3, 7, 2) |
|
| Day 15 (n= 0, 0, 1, 1, 4, 0, 7, 2) |
|
| Day 15 (n= 0, 1, 1, 1, 4, 3, 7, 2) |
|
| Day 15 (n= 0, 1, 1, 1, 4, 3, 7, 2) |
|
| Day 15 (n= 0, 0, 1, 1, 4, 3, 6, 2) |
|
| Day 15 (n= 0, 1, 1, 1, 3, 3, 4, 2) |
|
| Day 15 (n= 0, 1, 1, 1, 3, 3, 4, 2) |
|
| PR |
|
| SD |
|
| PD |
|