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The primary objective of this study is to determine the maximum tolerated dose (MTD) or the maximum administered dose (MAD) of Dasatinib (BMS-354825) in patients in Japan.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dasatinib (100 mg) | Experimental |
| |
| Dasatinib (150 mg) | Experimental |
| |
| Dasatinib (200 mg) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dasatinib | Drug | tablets, Oral, 100 mg, once daily for 4 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) and Maximum Acceptable Dose (MAD) of Dasatinib as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to Dasatinib Treatment | MAD: highest dose level at which >=1 DLTs were reported, MTD: dose one step lower than MAD. DLT: any of the following considered related to dasatinib during course 1:Grade 3(dose reduction by 1 dose level)/Grade 4:recurring nausea, vomiting or diarrhea; any other Grade >=3 non-hematologic toxicity except alopecia or fatigue;any grade toxicity requiring two dose reductions or participant's discontinuation; Grade 4 neutropenia <500 cells/mm^3 for >=5 consecutive days or febrile neutropenia; Grade 4 thrombocytopenia <25,000 cells/mm^3 or Grade 3 bleeding requiring platelet transfusion. | From start of the treatment i.e.Day 1 to end of Cycle 1 i.e. Day 30 (4 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs | AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to an AE were recorded. Drug-related AEs: events with a relationship to the study therapy of certain; probable; possible; not likely or unrelated. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Local Institution | Sayama | Osaka | 589-0014 | Japan | ||
| Local Institution |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dasatinib 100 mg | Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily. |
| FG001 | Dasatinib 150 mg | Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily. |
| FG002 | Dasatinib 200 mg | Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Dasatinib 100 mg | Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Median |
| 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 | Maximum Tolerated Dose (MTD) and Maximum Acceptable Dose (MAD) of Dasatinib as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to Dasatinib Treatment | MAD: highest dose level at which >=1 DLTs were reported, MTD: dose one step lower than MAD. DLT: any of the following considered related to dasatinib during course 1:Grade 3(dose reduction by 1 dose level)/Grade 4:recurring nausea, vomiting or diarrhea; any other Grade >=3 non-hematologic toxicity except alopecia or fatigue;any grade toxicity requiring two dose reductions or participant's discontinuation; Grade 4 neutropenia <500 cells/mm^3 for >=5 consecutive days or febrile neutropenia; Grade 4 thrombocytopenia <25,000 cells/mm^3 or Grade 3 bleeding requiring platelet transfusion. | All treated participants who received at least one dose of the study drug and were evaluable for DLT. | Posted | Number | participants | From start of the treatment i.e.Day 1 to end of Cycle 1 i.e. Day 30 (4 weeks) |
|
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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 | Dasatinib 100 mg | Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Perianal abscess | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA (11.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| BMS Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000069439 | Dasatinib |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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| Dasatinib | Drug | tablets, Oral, 150 mg, once daily, 4 weeks |
|
|
| Dasatinib | Drug | tablets, Oral, 200 mg, once daily for 4 weeks |
|
|
| From start of study drug therapy up to 30 days after the last dose. |
| Number of Participants With Grade 3 or 4 Hematology Abnormalities | Hematology abnormalities were graded per the National Cancer Institute (NCI) Common. Terminology Criteria (CTC) version 3.0 criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Absolute Neutrophil Count (ANC): Grade 3: 0.5 - <1.0*10^9/L, Grade 4: <0.5*10^9/L; lymphocytes: Grade 3: 0.2 - <0.5*10^9/L, Grade 4: <0.2*10^9/L. | From start of study drug therapy up to 30 days after the last dose. |
| Number of Participants With Grade 3-4 Serum Chemistry Abnormalities | Abnormalities were graded according to the NCI CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: phosphorous: Grade 3: 1.0-<2.0 mg/dL, Grade 4: <1.0 mg/dL; calcium: Grade 3: 6.0-<7.0 or >12.5-13.5 mg/dL, Grade 4: <0.6->13.5 mg/dL; magnesium: Grade 3: >3.0 - 8.0 mg/dL or >1.23 - 3.30 mmol/L, Grade 4: >8.0 mg/dL or >3.30 mmol/L; albumin: Grade 3: <2 g/dL or <20 g/L. | From start of study drug therapy up to 30 days after the last dose. |
| Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=10% Participants: Low Lymphocyte Count | Abnormalities were graded according to the NCI CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Most frequent hematology Grade 3 and 4 abnormalities occurring in >=10% participants were recorded. Grade 3 and 4 criteria are as follows: lymphocyte count: Grade 3: 0.2 - <0.5*10^9/L, Grade 4: <0.2*10^9/L. | From start of study drug therapy up to 30 days after the last dose. |
| Most Frequent Serum Chemistry Laboratory Abnormalities Occurring in >=10% Participants: High Magnesium | Abnormalities were graded according to the NCI-CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Most frequent (>=10%) serum laboratory abnormalities were recorded. The following definitions specify the NCI-CTC AE criteria for serum laboratory abnormalities in the data presented: magnesium: Grade 3: >3.0 - 8.0 mg/dL or >1.23 - 3.30 mmol/L, Grade 4: >8.0 mg/dL or >3.30 mmol/L. | From start of study drug therapy up to 30 days after the last dose. |
| Number of Participants With Clinically Meaningful Physical Examination Measures | Interim and final physical examinations were performed. The investigator used his/her clinical judgment to decide whether or not physical examination findings were clinically significant. | From screening, Day 1 in each treatment course and at the end of study |
| Number of Participants With Clinically Meaningful Vital Signs | Vital signs measurements (including blood pressure, body temperature and pulse rate) were recorded. The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs were clinically significant. | From screening, Day 1 , 8, 15 and 22 in the 1st treatment course, Day 8 and 22 in the second and subsequent courses and at the end of study |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | Standard 12-lead ECG was used to record selected ECG parameters like RR interval (the time between the two R waves in ECG), PR interval (interval measured from the beginning of the P wave to the beginning of the QRS complex; QRS complex is the name for some of the deflections seen on a typical ECG)), QRS duration, QT interval (time between onset of ventricular depolarization and end of ventricular repolarization), QT interval corrected for heart rate using Bazett's (QTcB) and Fridericia's (QTcF) formulas. | From screening Day -1, and at pre-dose, 1 and 4 hours (post-dose) on Days 1, 14 and 28 in first treatment course, at pre-dose, 1 and 4 hours (post-dose) during the second and fourth week in subsequent courses and at the end of study |
| Number of Participants With Clinically Significant Change in QT Interval Corrected for Heart Rate (QTcF) | QT interval corrected for heart rate (QTcF) was assessed using triplicate 12-lead serial ECGs. | Baseline, Day 1, Day 14 and Day 28 |
| Maximum Plasma Concentration (Cmax) of Dasatinib | Cmax was obtained from the plasma concentration versus time data after oral administration of dasatinib. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
| Area Under the Plasma-concentration-time Curve [AUC (INF)] of Dasatinib on Day 1 | AUC(INF), area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration within the dosing interval was calculated for Day 1. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Day 1 |
| AUC[TAU] of Dasatinib | Area under the plasma concentration-time curve within the dosing interval was determined. AUC(TAU), from time 0 to the time of the last measurable concentration (24 hours) was calculated for Day 1, 14, 28 respectively. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
| Time to Reach Maximum Observed Plasma Concentration of Dasatinib (Tmax) | Tmax, time to reach maximum observed plasma concentration of dasatinib was obtained directly from the plasma concentration versus time data. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
| Terminal Elimination Half-life (T-half) of Dasatinib | T-half of dasatinib was calculated using plasma concentration versus time data. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
| Accumulation Index (AI) of Dasatinib | AI of Dasatinib was calculated as ratio of geometric mean of AUC(TAU) (area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration) on Day 14 or Day 28 on Day 1. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
| Mean Apparent Oral Clearance (CLo) of Dasatinib | Apparent oral clearance was obtained from the plasma concentration versus time data. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28 |
| Mean Apparent Volume of Distribution (Vz/F) of Dasatinib | Apparent volume of distribution after oral dosing was obtained from plasma concentration versus time data. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28 |
| Cmax of Metabolite BMS-582691 | Maximum plasma concentration was obtained from plasma concentration versus time data of metabolite (BMS-582691). | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
| AUC (0-t) of Metabolite BMS-582691 | AUC (0-t) was calculated using plasma concentration values of metabolite at time 0 to the time of the last measurable concentration (t). | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
| Tmax of the Metabolite BMS-582691 | Tmax of the metabolite was obtained using plasma concentration versus time data of metabolite BMS-582691. | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
| Mean Urine Concentration of Urinary N-telopeptide Type 1 Collagen (NTx) Biological Marker | Urine NTx is a measure of bone metabolism. A decrease in the marker relative to baseline indicates a decrease in bone metabolism. Mean urine concentration of NTx biological marker was determined using enzyme linked immuno-sorbent assay (ELISA). | Urine samples were collected at baseline (Day -1) and 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28. |
| Mean Urine Concentration of Deoxypyridinoline (Dpyr) Biological Marker | Urine levels of DPyr is a measure of bone resorption. A decrease in Dpyr relative to the baseline indicates decrease in bone metabolism. Mean urine concentration of Dpyr biological marker was determined using ELISA. | Urine samples were collected at baseline (Day -1) and 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6 12 and 24 hours post dose on Days 14 and 28 |
| Mean Serum Concentration of Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP-5b) Biological Marker | TRACP-5b is a measure of bone metabolism. A decrease in TRACP-5b relative to the baseline indicates decrease in bone metabolism. Serum TRACP-5b was quantified with enzyme-linked-immunosorbent serologic assay (ELISA). | Serum samples were assessed at baseline (Day -1) and on Days 14 and 28 |
| Mean Serum Concentration of Bone Alkaline Phosphatase (BAP) Biological Marker | BAP is a measure of bone metabolism. A decrease in BAP relative to the baseline indicates decrease in bone metabolism. Serum BAP was quantified with ELISA. | Serum samples were assessed on baseline (Day -1), and pre-dose on Days 14, 28 |
| Number of Participants With Sarcoma (Src) and Phosphorylated Src (pSRc) Protein Expression in Peripheral Blood Mononuclear Cells (PBMC) | Src and pSrc protein expression was planned to be evaluated in PBMC for establishing PK/PD relationship between Src/pSrc protein expression in PBMC and exposure of BMS-354825. | Plasma samples were collected on baseline (Day -1), 0 hour (pre-dose), 1 and 4 hours (post-dose) on Days 1, 14 and 28 |
| Number of Participants With Complete Response (CR) or Partial Response (PR) | Tumor response was defined as the number of participants whose best response was CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: disappearance of all target/non-target lesions; PR: >= 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | Within 4 weeks of first study drug administration, thereafter recorded every 4 or 8 weeks. |
| Koto-Ku |
| Tokyo |
| 135-0063 |
| Japan |
| Participant's request to discontinuation |
|
| BG001 | Dasatinib 150 mg | Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily. |
| BG002 | Dasatinib 200 mg | Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Eastern Cooperative Oncology group (ECOG) Performance Status (PS) | The ECOG PS is used to assess disease severity. ECOG PS scores are, 0: fully active, able to carry on all pre-disease performance without restriction; 1: restricted physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2: ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3: capable of only limited self care, confined to bed or chair more than 50% of waking hours; 4: completely disabled, cannot carry on any self-care i.e. totally confined to bed or chair. | Number | Units on a scale |
|
| Dasatinib 100 mg |
Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily. |
| OG001 | Dasatinib 150 mg | Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily. |
| OG002 | Dasatinib 200 mg | Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily. |
|
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| Secondary | Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs | AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to an AE were recorded. Drug-related AEs: events with a relationship to the study therapy of certain; probable; possible; not likely or unrelated. | All participants who received at least one dose of the study drug (safety population). | Posted | Number | participants | From start of study drug therapy up to 30 days after the last dose. |
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|
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| Secondary | Number of Participants With Grade 3 or 4 Hematology Abnormalities | Hematology abnormalities were graded per the National Cancer Institute (NCI) Common. Terminology Criteria (CTC) version 3.0 criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Absolute Neutrophil Count (ANC): Grade 3: 0.5 - <1.0*10^9/L, Grade 4: <0.5*10^9/L; lymphocytes: Grade 3: 0.2 - <0.5*10^9/L, Grade 4: <0.2*10^9/L. | All participants who received at least one dose of the study drug. | Posted | Number | participants | From start of study drug therapy up to 30 days after the last dose. |
|
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|
| Secondary | Number of Participants With Grade 3-4 Serum Chemistry Abnormalities | Abnormalities were graded according to the NCI CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: phosphorous: Grade 3: 1.0-<2.0 mg/dL, Grade 4: <1.0 mg/dL; calcium: Grade 3: 6.0-<7.0 or >12.5-13.5 mg/dL, Grade 4: <0.6->13.5 mg/dL; magnesium: Grade 3: >3.0 - 8.0 mg/dL or >1.23 - 3.30 mmol/L, Grade 4: >8.0 mg/dL or >3.30 mmol/L; albumin: Grade 3: <2 g/dL or <20 g/L. | All participants who received at least one dose of the study drug. | Posted | Number | participants | From start of study drug therapy up to 30 days after the last dose. |
|
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| Secondary | Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=10% Participants: Low Lymphocyte Count | Abnormalities were graded according to the NCI CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Most frequent hematology Grade 3 and 4 abnormalities occurring in >=10% participants were recorded. Grade 3 and 4 criteria are as follows: lymphocyte count: Grade 3: 0.2 - <0.5*10^9/L, Grade 4: <0.2*10^9/L. | All treated participants who received at least one dose of the study drug. | Posted | Number | participants | From start of study drug therapy up to 30 days after the last dose. |
|
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| Secondary | Most Frequent Serum Chemistry Laboratory Abnormalities Occurring in >=10% Participants: High Magnesium | Abnormalities were graded according to the NCI-CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Most frequent (>=10%) serum laboratory abnormalities were recorded. The following definitions specify the NCI-CTC AE criteria for serum laboratory abnormalities in the data presented: magnesium: Grade 3: >3.0 - 8.0 mg/dL or >1.23 - 3.30 mmol/L, Grade 4: >8.0 mg/dL or >3.30 mmol/L. | All participants who received at least one dose of the study drug (safety population). | Posted | Number | participants | From start of study drug therapy up to 30 days after the last dose. |
|
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| Secondary | Number of Participants With Clinically Meaningful Physical Examination Measures | Interim and final physical examinations were performed. The investigator used his/her clinical judgment to decide whether or not physical examination findings were clinically significant. | All participants who received at least one dose of the study drug (safety population). Analysis for significant physical examination findings was not done. | Posted | Number | participants | From screening, Day 1 in each treatment course and at the end of study |
|
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| Secondary | Number of Participants With Clinically Meaningful Vital Signs | Vital signs measurements (including blood pressure, body temperature and pulse rate) were recorded. The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs were clinically significant. | All participants who received at least one dose of the study drug (safety population). | Posted | Number | participants | From screening, Day 1 , 8, 15 and 22 in the 1st treatment course, Day 8 and 22 in the second and subsequent courses and at the end of study |
|
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| Secondary | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | Standard 12-lead ECG was used to record selected ECG parameters like RR interval (the time between the two R waves in ECG), PR interval (interval measured from the beginning of the P wave to the beginning of the QRS complex; QRS complex is the name for some of the deflections seen on a typical ECG)), QRS duration, QT interval (time between onset of ventricular depolarization and end of ventricular repolarization), QT interval corrected for heart rate using Bazett's (QTcB) and Fridericia's (QTcF) formulas. | All participants who received at least one dose of the study drug (safety population). | Posted | Number | participants | From screening Day -1, and at pre-dose, 1 and 4 hours (post-dose) on Days 1, 14 and 28 in first treatment course, at pre-dose, 1 and 4 hours (post-dose) during the second and fourth week in subsequent courses and at the end of study |
|
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| Secondary | Number of Participants With Clinically Significant Change in QT Interval Corrected for Heart Rate (QTcF) | QT interval corrected for heart rate (QTcF) was assessed using triplicate 12-lead serial ECGs. | All participants who received at least one dose of the study drug (safety population). | Posted | Number | participants | Baseline, Day 1, Day 14 and Day 28 |
|
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| Secondary | Maximum Plasma Concentration (Cmax) of Dasatinib | Cmax was obtained from the plasma concentration versus time data after oral administration of dasatinib. | All treated participants with adequate pharmacokinetic (PK)profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Geometric Mean | Full Range | nanograms (ng)/ml | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
|
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| Secondary | Area Under the Plasma-concentration-time Curve [AUC (INF)] of Dasatinib on Day 1 | AUC(INF), area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration within the dosing interval was calculated for Day 1. | All treated participants with adequate PK profiles (PK population). | Posted | Geometric Mean | Full Range | ng*hours/ml | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Day 1 |
|
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| Secondary | AUC[TAU] of Dasatinib | Area under the plasma concentration-time curve within the dosing interval was determined. AUC(TAU), from time 0 to the time of the last measurable concentration (24 hours) was calculated for Day 1, 14, 28 respectively. | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Geometric Mean | Full Range | ng*hours/ml | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
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|
| Secondary | Time to Reach Maximum Observed Plasma Concentration of Dasatinib (Tmax) | Tmax, time to reach maximum observed plasma concentration of dasatinib was obtained directly from the plasma concentration versus time data. | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Median | Full Range | hours | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
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|
|
| Secondary | Terminal Elimination Half-life (T-half) of Dasatinib | T-half of dasatinib was calculated using plasma concentration versus time data. | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Mean | Standard Deviation | hours | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
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|
| Secondary | Accumulation Index (AI) of Dasatinib | AI of Dasatinib was calculated as ratio of geometric mean of AUC(TAU) (area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration) on Day 14 or Day 28 on Day 1. | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Geometric Mean | Full Range | ratio | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
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|
|
| Secondary | Mean Apparent Oral Clearance (CLo) of Dasatinib | Apparent oral clearance was obtained from the plasma concentration versus time data. | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Geometric Mean | Full Range | L/hour | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28 |
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|
|
| Secondary | Mean Apparent Volume of Distribution (Vz/F) of Dasatinib | Apparent volume of distribution after oral dosing was obtained from plasma concentration versus time data. | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Geometric Mean | Full Range | L | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28 |
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|
|
| Secondary | Cmax of Metabolite BMS-582691 | Maximum plasma concentration was obtained from plasma concentration versus time data of metabolite (BMS-582691). | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Geometric Mean | Full Range | ng/ml | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
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|
| Secondary | AUC (0-t) of Metabolite BMS-582691 | AUC (0-t) was calculated using plasma concentration values of metabolite at time 0 to the time of the last measurable concentration (t). | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Geometric Mean | Full Range | ng*hr/mL | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
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|
|
| Secondary | Tmax of the Metabolite BMS-582691 | Tmax of the metabolite was obtained using plasma concentration versus time data of metabolite BMS-582691. | All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Median | Full Range | hours | Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28 |
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|
|
| Secondary | Mean Urine Concentration of Urinary N-telopeptide Type 1 Collagen (NTx) Biological Marker | Urine NTx is a measure of bone metabolism. A decrease in the marker relative to baseline indicates a decrease in bone metabolism. Mean urine concentration of NTx biological marker was determined using enzyme linked immuno-sorbent assay (ELISA). | All treated participants with adequate pharmacodynamic (PD) profiles (PD population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Mean | Standard Deviation | nmol*bone collagen equivalent (BCE)/mmol | Urine samples were collected at baseline (Day -1) and 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28. |
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|
|
| Secondary | Mean Urine Concentration of Deoxypyridinoline (Dpyr) Biological Marker | Urine levels of DPyr is a measure of bone resorption. A decrease in Dpyr relative to the baseline indicates decrease in bone metabolism. Mean urine concentration of Dpyr biological marker was determined using ELISA. | All treated participants with adequate PD profiles (PD population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Mean | Standard Deviation | nanomol (nmol)/mL | Urine samples were collected at baseline (Day -1) and 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6 12 and 24 hours post dose on Days 14 and 28 |
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|
|
| Secondary | Mean Serum Concentration of Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP-5b) Biological Marker | TRACP-5b is a measure of bone metabolism. A decrease in TRACP-5b relative to the baseline indicates decrease in bone metabolism. Serum TRACP-5b was quantified with enzyme-linked-immunosorbent serologic assay (ELISA). | All treated participants with adequate PD profiles (PD population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Mean | Standard Deviation | U/L | Serum samples were assessed at baseline (Day -1) and on Days 14 and 28 |
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|
|
| Secondary | Mean Serum Concentration of Bone Alkaline Phosphatase (BAP) Biological Marker | BAP is a measure of bone metabolism. A decrease in BAP relative to the baseline indicates decrease in bone metabolism. Serum BAP was quantified with ELISA. | All treated participants with adequate PD profiles (PD population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively). | Posted | Mean | Standard Deviation | U/L | Serum samples were assessed on baseline (Day -1), and pre-dose on Days 14, 28 |
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|
|
| Secondary | Number of Participants With Sarcoma (Src) and Phosphorylated Src (pSRc) Protein Expression in Peripheral Blood Mononuclear Cells (PBMC) | Src and pSrc protein expression was planned to be evaluated in PBMC for establishing PK/PD relationship between Src/pSrc protein expression in PBMC and exposure of BMS-354825. | All treated participants with adequate pharmacodynamic profiles. Participants could not be evaluated as the test was discontinued due to difficulty in appropriate measurements. | Posted | Number | participants | Plasma samples were collected on baseline (Day -1), 0 hour (pre-dose), 1 and 4 hours (post-dose) on Days 1, 14 and 28 |
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|
| Secondary | Number of Participants With Complete Response (CR) or Partial Response (PR) | Tumor response was defined as the number of participants whose best response was CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: disappearance of all target/non-target lesions; PR: >= 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | All treated participants with measurable disease at baseline and received at least one dose of the study drug (efficacy population). | Posted | Number | participants | Within 4 weeks of first study drug administration, thereafter recorded every 4 or 8 weeks. |
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|
|
| 1 |
| 9 |
| 9 |
| 9 |
| EG001 | Dasatinib 150 mg | Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily. | 1 | 3 | 3 | 3 |
| EG002 | Dasatinib 200 mg | Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily. | 1 | 4 | 4 | 4 |
| Open fracture | Injury, poisoning and procedural complications | MedDRA (11.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Extrasystoles | Cardiac disorders | MedDRA (11.0) | Systematic Assessment |
|
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (11.0) | Systematic Assessment |
|
| Conjunctival hemorrhage | Eye disorders | MedDRA (11.0) | Systematic Assessment |
|
| Visual disturbance | Eye disorders | MedDRA (11.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Epigastric discomfort | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Painful defecation | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Edema | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Face edema | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Peripheral coldness | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA (11.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
|
| Enteritis infectious | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood calcium decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood urine present | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Protein urine | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood magnesium increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Hemoglobin decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Protein total decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Red blood cell count decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Protein urine present | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Hematocrit decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
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| Prothrombin time ratio increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Cell marker increased | Investigations | MedDRA (11.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA (11.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (11.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
|
| Facial nerve disorder | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (11.0) | Systematic Assessment |
|
| Breast hemorrhage | Reproductive system and breast disorders | MedDRA (11.0) | Systematic Assessment |
|
| Gynecomastia | Reproductive system and breast disorders | MedDRA (11.0) | Systematic Assessment |
|
| Nipple swelling | Reproductive system and breast disorders | MedDRA (11.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Dyspnea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Pharyngeal erythema | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Pharyngolaryngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Bronchial wall thickening | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Hair colour changes | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (11.0) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (11.0) | Systematic Assessment |
|
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| Title | Measurements |
|---|---|
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| SAEs |
|
| Drug-related AEs |
|
| All AEs Leading to Discontinuation |
|
|
| Title | Measurements |
|---|---|
|
| High magnesium |
|
| Low albumin |
|
| Day 14 (n = 5, 4, 2) |
|
| Day 28 (n= 3, 2, 2) |
|
| Day 14 (n = 5, 4, 2) |
|
| Day 28 (n= 3, 2, 2) |
|
|
| Day 28 (n= 3, 2, 2) |
|
|
| Day 28 (n= 3, 2, 2) |
|
|
| Day 28 (n= 3, 2, 2) |
|
| Day 28 (n= 3, 2, 2) |
|
|
| Day 28 (n= 3, 1, 2) |
|
|
| Day 28 (n= 3, 1, 2) |
|
|
| Day 28 (n= 3, 1, 2) |
|
|
| Day 28 (n= 3, 2, 2) |
|
|
| Day 28 (n= 3, 2, 2) |
|
| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
|