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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-002260-24 | EudraCT Number | ||
| U1111-1163-9720 | Registry Identifier | WHO |
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This is an Open-Label, Multicenter, Dose Escalation, First-in-Human Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MLN0264 | Experimental | MLN0264 starting dose 0.3 mg/kg escalated until Maximum Tolerated Dose (MTD) was determined, 30-minute infusion, on Day 1 of each 21-Day treatment cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MLN0264 | Drug | MLN0264 30-minute infusion on Day 1 of each treatment cycle |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) | DLT was defined as any of the following Adverse Events (AEs) that occur and are considered by the investigator to be related to therapy.
| From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months |
| Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. | From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months |
| Maximum Tolerated Dose (MTD) of MLN0264 |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response | The percentage of participants in each best overall response category, was determined using the Modified Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response: Disappearance of all target lesions and all non-target lesions and normalization of tumor marker level. Partial Response: At least a 30% decrease in the sum of the Longest Diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the start or the appearance of one or more new lesions. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. |
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Inclusion Criteria:
Exclusion Criteria:
Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
Participants with Gastrointestinal malignancies expressing guanylyl cyclase C were enrolled in the dose escalation phase: 0.3, 0.6, 1.2, 1.5, 1.8, 2.1 and 2.4 mg/kg to determine the maximum tolerated dose (MTD). MTD was established and participants were enrolled in the mCRC expansion phase. 3 participants were in both the 1.8 mg/kg and mCRC arms.
Participants took part in the study at 4 investigative sites in the United States and Spain from 11 June 2012 to 12 February 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | MLN0264 0.3 mg/kg | MLN0264 0.3 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| FG001 | MLN0264 0.6 mg/kg | MLN0264 0.6 mg/kg, 30-minute intravenous IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| FG002 | MLN0264 1.2 mg/kg | MLN0264 1.2 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| FG003 | MLN0264 1.5 mg/kg | MLN0264 1.5 mg/kg, 30-minute intravenous IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| FG004 | MLN0264 1.8 mg/kg | MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| FG005 | MLN0264 2.1 mg/kg | MLN0264 2.1 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| FG006 | MLN0264 2.4 mg/kg | MLN0264 2.4 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| FG007 | MLN0264 1.8 mg/kg (mCRC Expansion) | MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year in participants with metastatic colorectal (rectal, colon, or colorectal) cancer (mCRC). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Escalation Phase |
|
| ||||||||||||||||||
| mCRC Expansion Phase |
|
Safety population included all participants who received at least 1 dose of study drug. A total of 41 participants participated in the study. There were 3 participants who participated in both phases of the study and are only counted once.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants who participated in the Dose Escalation and mCRC Expansion Phases. |
| 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 With Dose-Limiting Toxicities (DLTs) | DLT was defined as any of the following Adverse Events (AEs) that occur and are considered by the investigator to be related to therapy.
| DLT evaluable Population: participants enrolled in the Dose Escalation phase of the study who either experienced a DLT during Cycle 1 or received a scheduled Cycle 1 dose and completed all study procedures in Cycle 1 without DLT. | Posted | Number | participants | From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months |
From the time informed consent is signed through 30 days after the last dose of study drug (approximately 9 months)
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 | MLN0264 0.3 mg/kg | MLN0264 0.3 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Clinical Science | Takeda | +1-877-825-3327 | clinicaltrialregistry@tpna.com |
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| ID | Term |
|---|---|
| C000626278 | indusatumab |
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MTD of MLN0264 was determined. Decisions regarding dose escalation were made based on any DLT that occurred during the first cycle of treatment.
| Every 3 weeks until MTD is established, approximately 9 months |
| Cmax: Maximum Observed Serum Concentration for MLN0264 | Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably. | Cycle 1: Day 1 pre-dose to Day 21 post-dose |
| Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably. | Cycle 1: Day 1 pre-dose to Day 21 post-dose |
| AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MLN0246 | Area under the drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably. | Cycle 1: Day 1 pre-dose to 21 Days post-dose |
| AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MMAE | Area under the plasma drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably. | Cycle 1: Day 1 pre-dose to 21 Days post-dose |
| At the completion of every second cycle up to 12 cycles (approximately 9 months). Each cycle is a 21 days cycle |
| Number of Participants With Antitherapeutic Antibodies (ATA) | Blood was collected and sent to a laboratory to determine the immunogenicity, whether binding antibodies to MLN0264 were present (ATA development). | Day 1 of every 21 days cycle and at End of study (EOS) approximately 9 months |
| Symptomatic Deterioration |
|
| Withdrawal by Subject |
|
| Progression Disease |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Height | Height data is only available for 39 participants. | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Surface Area | Body surface area data is only available for 39 participants. | Mean | Standard Deviation | m^2 |
|
| ID | Title | Description |
|---|---|---|
| OG000 | MLN0264 0.3 mg/kg | MLN0264 0.3 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| OG001 | MLN0264 0.6 mg/kg | MLN0264 0.6 mg/kg, 30-minute intravenous IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| OG002 | MLN0264 1.2 mg/kg | MLN0264 1.2 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| OG003 | MLN0264 1.5 mg/kg | MLN0264 1.5 mg/kg, 30-minute intravenous IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| OG004 | MLN0264 1.8 mg/kg | MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| OG005 | MLN0264 2.1 mg/kg | MLN0264 2.1 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
| OG006 | MLN0264 2.4 mg/kg | MLN0264 2.4 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. |
|
|
| Primary | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. | Safety Analysis Set included all participants who received at least one dose of study drug. | Posted | Number | participants | From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months |
|
|
|
| Primary | Maximum Tolerated Dose (MTD) of MLN0264 | MTD of MLN0264 was determined. Decisions regarding dose escalation were made based on any DLT that occurred during the first cycle of treatment. | DLT evaluable Population: participants enrolled in the Dose Escalation phase of the study who either experienced a DLT during Cycle 1 or received a scheduled Cycle 1 dose and completed all study procedures in Cycle 1 without DLT. | Posted | Number | mg/kg | Every 3 weeks until MTD is established, approximately 9 months |
|
|
|
| Secondary | Best Overall Response | The percentage of participants in each best overall response category, was determined using the Modified Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response: Disappearance of all target lesions and all non-target lesions and normalization of tumor marker level. Partial Response: At least a 30% decrease in the sum of the Longest Diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the start or the appearance of one or more new lesions. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. | Response Evaluable Population is defined as patients with measureable disease who receive any amount of MLN0264 and have at least 1 post-Baseline response assessment. | Posted | Number | percentage of participants | At the completion of every second cycle up to 12 cycles (approximately 9 months). Each cycle is a 21 days cycle |
|
|
|
| Secondary | Number of Participants With Antitherapeutic Antibodies (ATA) | Blood was collected and sent to a laboratory to determine the immunogenicity, whether binding antibodies to MLN0264 were present (ATA development). | Posted | Number | participants | Day 1 of every 21 days cycle and at End of study (EOS) approximately 9 months |
|
|
|
| Primary | Cmax: Maximum Observed Serum Concentration for MLN0264 | Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably. | Participants from the Pharmacokinetic (PK)-evaluable Population, all participants with sufficient dosing and reliable PK data to estimate PK parameters. | Posted | Geometric Mean | Full Range | μg/mL | Cycle 1: Day 1 pre-dose to Day 21 post-dose |
|
|
|
| Primary | Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably. | Participants from the Pharmacokinetic (PK)-evaluable Population, all participants with sufficient dosing and reliable PK data to estimate PK parameters. | Posted | Geometric Mean | Full Range | ng/mL | Cycle 1: Day 1 pre-dose to Day 21 post-dose |
|
|
|
| Primary | AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MLN0246 | Area under the drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably. | Participants from the PK-evaluable Population, all participants with sufficient dosing and reliable PK data to estimate PK parameters. | Posted | Geometric Mean | Full Range | day*μg/mL | Cycle 1: Day 1 pre-dose to 21 Days post-dose |
|
|
|
| Primary | AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MMAE | Area under the plasma drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably. | Participants from the PK-evaluable Population, all participants with sufficient dosing and reliable PK data to estimate PK parameter AUC0-21 days. | Posted | Geometric Mean | Full Range | day*ng/mL | Cycle 1: Day 1 pre-dose to 21 Days post-dose |
|
|
|
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | MLN0264 0.6 mg/kg | MLN0264 0.6 mg/kg, 30-minute intravenous IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. | 2 | 2 | 2 | 2 |
| EG002 | MLN0264 1.2 mg/kg | MLN0264 1.2 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. | 1 | 2 | 2 | 2 |
| EG003 | MLN0264 1.5 mg/kg | MLN0264 1.5 mg/kg, 30-minute intravenous IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. | 0 | 2 | 2 | 2 |
| EG004 | MLN0264 1.8 mg/kg | MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. | 10 | 28 | 28 | 28 |
| EG005 | MLN0264 2.1 mg/kg | MLN0264 2.1 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. | 2 | 4 | 4 | 4 |
| EG006 | MLN0264 2.4 mg/kg | MLN0264 2.4 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, until disease progression or unacceptable toxicity or up to 1 year. | 1 | 1 | 1 | 1 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Colonic obstruction | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Psoas abscess | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Troponin T increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Acidosis | 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 |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Oesophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment | One treatment-emergent death occurred during the Dose Escalation Phase and is not related. |
|
| Convulsion | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (16.0) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (16.0) | Systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | 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 bilirubin increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Blood magnesium decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Carbon dioxide increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Mean cell haemoglobin concentration decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Mean cell volume decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Monocyte count decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Monocyte count increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Neutrophil count increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Decreased appetite | 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 |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA (16.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| CR + PR |
|
| Stable Disease |
|
| Progressive Disease |
|