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The purpose of this study is to test how rifampin affects the removal of BMS-247550 (ixabepilone) from the body.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ixabepilone + rifampin | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ixabepilone | Drug | ixabepilone solution, intravenous, 40 mg/m2, once every 3 weeks until disease progression |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | Cmax was obtained directly from the concentration-time data. | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [INF]) | AUC (INF) was obtained directly from the concentration-time data. | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
| Time Taken for Plasma Concentration to Reduce by 50 Percent or Apparent Terminal Plasma Elimination Half-life (T Half) | T half was obtained directly from the concentration-time data. | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
| Mean Residence Time Adjusted for Infusion Time (MRT [INF]) | (MRT [INF]) was obtained directly from the concentration-time data. | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
| Total Body Clearance (CLT) | CLT was obtained directly from the concentration-time data. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Died and Who Experienced Other Serious AEs (SAEs), Grade 3-4 AEs, Drug-related AEs and AEs Leading to Study Drug Discontinuation | AEs:new untoward medical occurrences/worsening of pre-existing medical condition,whether or not related to study drug.SAE:AE resulting in death;life threatening;resulted in persistent/significant disability/incapacity;resulted in/prolonged existing hospitalization;a congenital anomaly/birth defect;overdose.Drug-related AEs: relationship to drug of certain;probable;possible;or missing.Participants who discontinued study due to AE were also recorded.AEs graded using National Cancer Institute (NCI) Common Toxicity Criteria (CTC),v3:Grade 1=mild,2=moderate, 3=severe,4=life threatening,5=death. |
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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 |
|---|---|---|---|---|---|---|
| The Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
19 participants were enrolled and 15 were treated with the study drug. 4 participants were not treated (1 participant due to an adverse event [AE] and 3 participants for no longer meeting study criteria)
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles. |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Maximum Plasma Concentration (Cmax) | Cmax was obtained directly from the concentration-time data. | Of the 15 patients in each group, only those with evaluable pharmacokinetic (PK) results are presented. | Posted | Geometric Mean | 90% Confidence Interval | nanogram (ng)/millilter(mL) | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
|
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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 | All Participants | All treated participants who received at least 1 dose of study drug. On Day 1 of Cycle 1, each participant received a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Day 15, participants were administered an oral dose of 600 mg rifampin in the clinic and on Days 16-21, participants self-administered rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| MYOCARDIAL ISCHAEMIA | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| PHOTOPHOBIA | Eye disorders | MedDRA 12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C430592 | ixabepilone |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Rifampin | Drug | rifampin tablets, oral, 600 mg once daily, only on Days 15 to 21 of Cycle 1 and Days 1 to 7 of Cycle 2 |
|
| Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
| Volume of Distribution at Steady-state (Vss) | Vss was obtained directly from the concentration-time data. | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
| Time to Reach Maximum Observed Concentration (T Max) | T max was obtained directly from the concentration-time data. | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T]) | AUC (0-T) was obtained directly from the concentration-time data. | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
| Urine 6B-Hydroxycortisol to Cortisol Ratio on Day -1 | The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1. | Day -1 (0-8 hours and 8-24 hours), 24 hours before starting of ixabepilone administration. |
| Urine 6B-Hydroxycortisol to Cortisol Ratio on Day 22 | The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1. | Day 22 (0-8 hours and 8-24 hours) during ixabepilone and rifampin co-administration. |
| From Day 1 to 30 days after the last dose of study drug. |
| Number of Participants With Grade 3-4 Hematology Abnormalities | Abnormalities occurring at any time during the study were graded per NCI CTC, v3.0 criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are given below. Neutrophils: Grade 3: 0.5 - <1.0x10^9/L, Grade 4: <0.5x10^9/L. Leukocytes: Grade 3: 1.0 - <2.0x10^9/L, Grade 4: <1.0x10^9/L. Neutrophils + bands (absolute): Grade 3: 0.5 - <1.0x10^9/L, Grade 4: <0.5x10^9/L. Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Lymphocytes: Grade 3: 0.2 - <0.5x10^9/L, Grade 4: <0.2x10^9/L. Platelets: Grade 3: 25.0 - <50.0x10^9/L, Grade 4: <25.0x10. | Screening, Day 1, Day 8, Day 15, Day 22 and Day 29-36. |
| Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous | Abnormalities occurring at any time during the study were graded per the NCI CTC (1=mild, 2=moderate, 3=severe, 4=life threatening). Grade 3 and 4 criteria were as follows: Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase: Grade 3: >5-20 x upper limit of normal (ULN), Grade 4: >20 x ULN. Bilirubin: Grade 3: >3-10 x ULN, Grade 4: >10 x ULN. Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC). Creatinine: Grade 3: >3-6 x ULN, Grade 4: >6 x ULN. Phosphorous: Grade 3: 1-<2mg/dL, Grade 4: <1mg/dL. | Screening, Days 1 and 22. |
| Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid. | Abnormalities occurring at any time during the study were graded per NCI CTC (1=mild, 2=moderate, 3=severe, 4=life threatening). Grade 3 and 4 criteria were as follows:Calcium: Grade 3: 6-<7 or >12.5-13.5mg/dL, Grade 4:<6 or >13.5mg/dL. Magnesium: Grade 3:0.6-<0.8 or >2.46-6.6mEq/L, Grade 4:<0.6 or >6.6mEq/L. Potassium: Grade 3:2.5-<3 or >6-7mmol/L, Grade 4:<2.5 or >7.0 mmol/L. Sodium: Grade 3:120-<130 or >155-160 mEq/L, Grade 4:<120 or >160mEq/L. Glucose: Grade 3:30-<40 or >250-500mg/dL, Grade 4:<30 or >500mg/dL. Uric acid: Grade 3:>ULN-10mg/dL with physiologic consequences, Grade 4:>10mg/dL. | Screening, Days 2 and 22. |
| Number of Participants With Clinically Meaningful Vital Signs Measures | Vital signs were recorded throughout the study and included investigations related to body temperature, respiratory rate, seated blood pressure (systolic and diastolic), and heart rate. Normal ranges for the above are as follows: heart rate: 40 - 125 beats per minute (bpm); systolic BP: 65 - 200 millimeters of mercury (mmHg); diastolic BP: 40 - 120 mmHg; respiratory rate: 10 - 25 breaths per minute; temperature: 95 - 105F or 35 - 40.5C. The abnormalities displayed here are those considered "clinically significant" by the investigator and include abnormalities recorded at any time during study. | From screening to the off treatment visit. |
| Number of Participants With Abnormal Physical Examination Findings | Physical examination included height (screening only),weight,BSA,Eastern Cooperative Oncology Group Performance Status (ECOG PS),tendon reflexes,sensory function,motor strength. ECOG PS used to assess disease severity:score of 0 is fully active;1 is restricted physically strenuous activity;2 is ambulatory but unable to work;3 is capable of only limited self care;4 is completely disabled;5 is dead. Normal ranges:height:137-200cm or 54-79 inches;weight:40-135kg or 88-298 pounds (lbs);ECOG Scale:0-4. Abnormalities displayed here are those considered "clinically significant" by the investigator. | From screening to the off treatment visit. |
| QT Interval Corrected for Heart Rate (QTcF) | QT interval corrected for heart rate (QTcF) was assessed using triplicate 12-lead serial electrocardiograms (ECGs) that were performed at selected times after the first dose of ixabepilone without rifampin and at matched times prior to the first dose of ixabepilone. Abnormalities occurring at any time during the study were recorded. | Data collected at 0, 1.5, 3, 4, 6, 8 and 24 hours after start of infusion. |
| Number of Participants With Identified ECG Abnormalities | Triplicate 12-lead serial ECGs were performed pre-dose (just prior to infusion), 1.5, 3 (just prior to end of the infusion even if infusion lasted for less than or more than planned 3 hrs), 4, 6, 8 and 24 hrs after start of ixabepilone infusion. Triplicate 12-lead serial ECGs were also to be performed on the date prior to dosing at times approximating post-dose schedule (pre-dose triplicate set of ECGs also qualified as the 24-hr baseline ECGs). Normal ranges for ECG are as follows: heart rate: 40 - 125 bpm; PR: 0.1 - 0.2 msec; QRS: 0.06 - 0.12 msec; QTC: 0.3 - 0.45 msec; QT: 0.3 - 0.5 msec. | Data collected at screening, Day -1 and Day 1 (at 0, 1.5, 3, 4, 6, 8 and 24 hours) after start of infusion. |
| Physician Decision |
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| years |
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| Age, Customized | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Body surface area (BSA) continuous | BSA is the measured or calculated surface of a human body. | Mean | Standard Deviation | square meter |
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| Height continuous | Mean | Standard Deviation | centimeter |
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| Weight continuous | Mean | Standard Deviation | kilogram |
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| OG001 |
| Ixabepilone + Rifampin |
Having already received ixabepilone on Day 1 of Cycle 1 (see the "ixabepilone" treatment arm), participants were administered an oral dose of 600 mg rifampin on in the clinic on Day 15. On Days 16-21, participants self-administered rifampin once daily, at least 1 hour before or 2 hours after the ingestion of food. On Day 22 (Cycle 2), participants were administered an oral dose of 600 mg of rifampin while in a fasted state in the clinic. Participants were then administered a single 3-hour IV infusion of ixabepilone 40 mg/m^2. On Days 23-28, participants self-administered a 600-mg oral dose of rifampin once daily at least 1 hour before or 2 hours after the ingestion of food. During Cycle 3 and beyond, participants received a single 3-hour IV infusion of ixabepilone at a dose of 40 mg/m^2 (unless their dose had been reduced) on Day 1 of each 21-day cycle for a maximum of 6 full cycles. |
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| Primary | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [INF]) | AUC (INF) was obtained directly from the concentration-time data. | All treated participants who were evaluable for PK analysis. | Posted | Geometric Mean | 90% Confidence Interval | nanogram (ng)*hour(hr)/mL | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
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| Secondary | Number of Participants Who Died and Who Experienced Other Serious AEs (SAEs), Grade 3-4 AEs, Drug-related AEs and AEs Leading to Study Drug Discontinuation | AEs:new untoward medical occurrences/worsening of pre-existing medical condition,whether or not related to study drug.SAE:AE resulting in death;life threatening;resulted in persistent/significant disability/incapacity;resulted in/prolonged existing hospitalization;a congenital anomaly/birth defect;overdose.Drug-related AEs: relationship to drug of certain;probable;possible;or missing.Participants who discontinued study due to AE were also recorded.AEs graded using National Cancer Institute (NCI) Common Toxicity Criteria (CTC),v3:Grade 1=mild,2=moderate, 3=severe,4=life threatening,5=death. | All treated participants. | Posted | Number | participants | From Day 1 to 30 days after the last dose of study drug. |
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| Secondary | Number of Participants With Grade 3-4 Hematology Abnormalities | Abnormalities occurring at any time during the study were graded per NCI CTC, v3.0 criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are given below. Neutrophils: Grade 3: 0.5 - <1.0x10^9/L, Grade 4: <0.5x10^9/L. Leukocytes: Grade 3: 1.0 - <2.0x10^9/L, Grade 4: <1.0x10^9/L. Neutrophils + bands (absolute): Grade 3: 0.5 - <1.0x10^9/L, Grade 4: <0.5x10^9/L. Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Lymphocytes: Grade 3: 0.2 - <0.5x10^9/L, Grade 4: <0.2x10^9/L. Platelets: Grade 3: 25.0 - <50.0x10^9/L, Grade 4: <25.0x10. | All treated participants. | Posted | Number | participants | Screening, Day 1, Day 8, Day 15, Day 22 and Day 29-36. |
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| Secondary | Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous | Abnormalities occurring at any time during the study were graded per the NCI CTC (1=mild, 2=moderate, 3=severe, 4=life threatening). Grade 3 and 4 criteria were as follows: Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase: Grade 3: >5-20 x upper limit of normal (ULN), Grade 4: >20 x ULN. Bilirubin: Grade 3: >3-10 x ULN, Grade 4: >10 x ULN. Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC). Creatinine: Grade 3: >3-6 x ULN, Grade 4: >6 x ULN. Phosphorous: Grade 3: 1-<2mg/dL, Grade 4: <1mg/dL. | All treated participants. | Posted | Number | participants | Screening, Days 1 and 22. |
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| Primary | Time Taken for Plasma Concentration to Reduce by 50 Percent or Apparent Terminal Plasma Elimination Half-life (T Half) | T half was obtained directly from the concentration-time data. | All treated participants who were evaluable for PK analysis. | Posted | Mean | Standard Deviation | Hrs | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
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| Primary | Mean Residence Time Adjusted for Infusion Time (MRT [INF]) | (MRT [INF]) was obtained directly from the concentration-time data. | All treated participants who were evaluable for PK analysis. | Posted | Mean | Standard Deviation | Hrs | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
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| Primary | Total Body Clearance (CLT) | CLT was obtained directly from the concentration-time data. | All treated participants who were evaluable for PK analysis. | Posted | Mean | Standard Deviation | Litres(L)/hr | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
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| Primary | Volume of Distribution at Steady-state (Vss) | Vss was obtained directly from the concentration-time data. | All treated participants who were evaluable for PK analysis. | Posted | Mean | Standard Deviation | L | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
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| Primary | Time to Reach Maximum Observed Concentration (T Max) | T max was obtained directly from the concentration-time data. | All treated participants who were evaluable for PK analysis. | Posted | Median | Full Range | Hrs | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
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| Secondary | Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid. | Abnormalities occurring at any time during the study were graded per NCI CTC (1=mild, 2=moderate, 3=severe, 4=life threatening). Grade 3 and 4 criteria were as follows:Calcium: Grade 3: 6-<7 or >12.5-13.5mg/dL, Grade 4:<6 or >13.5mg/dL. Magnesium: Grade 3:0.6-<0.8 or >2.46-6.6mEq/L, Grade 4:<0.6 or >6.6mEq/L. Potassium: Grade 3:2.5-<3 or >6-7mmol/L, Grade 4:<2.5 or >7.0 mmol/L. Sodium: Grade 3:120-<130 or >155-160 mEq/L, Grade 4:<120 or >160mEq/L. Glucose: Grade 3:30-<40 or >250-500mg/dL, Grade 4:<30 or >500mg/dL. Uric acid: Grade 3:>ULN-10mg/dL with physiologic consequences, Grade 4:>10mg/dL. | All treated participants. | Posted | Number | Participants | Screening, Days 2 and 22. |
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| Primary | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T]) | AUC (0-T) was obtained directly from the concentration-time data. | All treated participants who were evaluable for PK analysis. | Posted | Mean | Standard Deviation | nanogram (ng)*hr/mL | Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration. |
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| Primary | Urine 6B-Hydroxycortisol to Cortisol Ratio on Day -1 | The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1. | All treated participants who were evaluable for PK analysis. | Posted | Mean | Standard Deviation | Ratio | Day -1 (0-8 hours and 8-24 hours), 24 hours before starting of ixabepilone administration. |
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| Secondary | Number of Participants With Clinically Meaningful Vital Signs Measures | Vital signs were recorded throughout the study and included investigations related to body temperature, respiratory rate, seated blood pressure (systolic and diastolic), and heart rate. Normal ranges for the above are as follows: heart rate: 40 - 125 beats per minute (bpm); systolic BP: 65 - 200 millimeters of mercury (mmHg); diastolic BP: 40 - 120 mmHg; respiratory rate: 10 - 25 breaths per minute; temperature: 95 - 105F or 35 - 40.5C. The abnormalities displayed here are those considered "clinically significant" by the investigator and include abnormalities recorded at any time during study. | All treated participants. | Posted | Number | participants | From screening to the off treatment visit. |
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| Primary | Urine 6B-Hydroxycortisol to Cortisol Ratio on Day 22 | The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1. | All treated participants who were evaluable for PK analysis. | Posted | Median | Standard Deviation | Ratio | Day 22 (0-8 hours and 8-24 hours) during ixabepilone and rifampin co-administration. |
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| Secondary | Number of Participants With Abnormal Physical Examination Findings | Physical examination included height (screening only),weight,BSA,Eastern Cooperative Oncology Group Performance Status (ECOG PS),tendon reflexes,sensory function,motor strength. ECOG PS used to assess disease severity:score of 0 is fully active;1 is restricted physically strenuous activity;2 is ambulatory but unable to work;3 is capable of only limited self care;4 is completely disabled;5 is dead. Normal ranges:height:137-200cm or 54-79 inches;weight:40-135kg or 88-298 pounds (lbs);ECOG Scale:0-4. Abnormalities displayed here are those considered "clinically significant" by the investigator. | All treated participants. | Posted | Number | participants | From screening to the off treatment visit. |
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|
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| Secondary | QT Interval Corrected for Heart Rate (QTcF) | QT interval corrected for heart rate (QTcF) was assessed using triplicate 12-lead serial electrocardiograms (ECGs) that were performed at selected times after the first dose of ixabepilone without rifampin and at matched times prior to the first dose of ixabepilone. Abnormalities occurring at any time during the study were recorded. | All participants treated with ixabepilone. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively. | Posted | Mean | 90% Confidence Interval | millisecond | Data collected at 0, 1.5, 3, 4, 6, 8 and 24 hours after start of infusion. |
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|
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| Secondary | Number of Participants With Identified ECG Abnormalities | Triplicate 12-lead serial ECGs were performed pre-dose (just prior to infusion), 1.5, 3 (just prior to end of the infusion even if infusion lasted for less than or more than planned 3 hrs), 4, 6, 8 and 24 hrs after start of ixabepilone infusion. Triplicate 12-lead serial ECGs were also to be performed on the date prior to dosing at times approximating post-dose schedule (pre-dose triplicate set of ECGs also qualified as the 24-hr baseline ECGs). Normal ranges for ECG are as follows: heart rate: 40 - 125 bpm; PR: 0.1 - 0.2 msec; QRS: 0.06 - 0.12 msec; QTC: 0.3 - 0.45 msec; QT: 0.3 - 0.5 msec. | All participants treated with ixabepilone. | Posted | Number | Participants | Data collected at screening, Day -1 and Day 1 (at 0, 1.5, 3, 4, 6, 8 and 24 hours) after start of infusion. |
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|
|
| 4 |
| 15 |
| 14 |
| 15 |
| HYPERTENSION | Vascular disorders | MedDRA 12.0 | Systematic Assessment |
|
| HYPERSENSITIVITY | Immune system disorders | MedDRA 12.0 | Systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| CHEST PAIN | General disorders | MedDRA 12.0 | Systematic Assessment |
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| TUMOUR PAIN | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.0 | Systematic Assessment |
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| LACRIMATION INCREASED | Eye disorders | MedDRA 12.0 | Systematic Assessment |
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| HAEMOGLOBIN | Investigations | MedDRA 12.0 | Systematic Assessment |
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| PLATELET COUNT | Investigations | MedDRA 12.0 | Systematic Assessment |
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| NEUTROPHIL COUNT | Investigations | MedDRA 12.0 | Systematic Assessment |
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| WEIGHT DECREASED | Investigations | MedDRA 12.0 | Systematic Assessment |
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| HAEMOGLOBIN DECREASED | Investigations | MedDRA 12.0 | Systematic Assessment |
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| WHITE BLOOD CELL COUNT | Investigations | MedDRA 12.0 | Systematic Assessment |
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| PLATELET COUNT DECREASED | Investigations | MedDRA 12.0 | Systematic Assessment |
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| NEUTROPHIL COUNT DECREASED | Investigations | MedDRA 12.0 | Systematic Assessment |
|
| WHITE BLOOD CELL COUNT DECREASED | Investigations | MedDRA 12.0 | Systematic Assessment |
|
| WHITE BLOOD CELL COUNT INCREASED | Investigations | MedDRA 12.0 | Systematic Assessment |
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| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 12.0 | Systematic Assessment |
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| PALLOR | Vascular disorders | MedDRA 12.0 | Systematic Assessment |
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| FLUSHING | Vascular disorders | MedDRA 12.0 | Systematic Assessment |
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| HOT FLUSH | Vascular disorders | MedDRA 12.0 | Systematic Assessment |
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| HYPOTENSION | Vascular disorders | MedDRA 12.0 | Systematic Assessment |
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| ANXIETY | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
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| INSOMNIA | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
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| DEPRESSION | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
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| RESTLESSNESS | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
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| HEPATOMEGALY | Hepatobiliary disorders | MedDRA 12.0 | Systematic Assessment |
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| HYPERSENSITIVITY | Immune system disorders | MedDRA 12.0 | Systematic Assessment |
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| TREMOR | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| AREFLEXIA | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| DYSGEUSIA | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| PARAESTHESIA | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| SENSORY DISTURBANCE | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| NEUROPATHY PERIPHERAL | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| RESTLESS LEGS SYNDROME | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| PERIPHERAL SENSORY NEUROPATHY | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| RETCHING | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| DIARRHOEA | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| DRY MOUTH | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| DYSPHAGIA | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| ORAL PAIN | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| STOMATITIS | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| CONSTIPATION | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| HAEMORRHOIDS | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| RHINITIS | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| ORAL CANDIDIASIS | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| ANOREXIA | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| HYPOCALCAEMIA | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| HYPERGLYCAEMIA | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| HYPOMAGNESAEMIA | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| HYPOALBUMINAEMIA | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| HYPOPHOSPHATAEMIA | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| ANAEMIA | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
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| LYMPHOPENIA | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
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| NEUTROPENIA | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
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| THROMBOCYTOPENIA | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
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| RASH | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| ALOPECIA | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| URTICARIA | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| HYPERHIDROSIS | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| SKIN IRRITATION | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| ADNEXA UTERI PAIN | Reproductive system and breast disorders | MedDRA 12.0 | Systematic Assessment |
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| FALL | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
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| EXCORIATION | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
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| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| BONE PAIN | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| NECK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| LIMB DISCOMFORT | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| MUSCULAR WEAKNESS | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| HAEMOPTYSIS | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| NASAL CONGESTION | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| DYSPNOEA EXERTIONAL | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| PAIN | General disorders | MedDRA 12.0 | Systematic Assessment |
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| CHILLS | General disorders | MedDRA 12.0 | Systematic Assessment |
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| FATIGUE | General disorders | MedDRA 12.0 | Systematic Assessment |
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| FEELING HOT | General disorders | MedDRA 12.0 | Systematic Assessment |
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| EARLY SATIETY | General disorders | MedDRA 12.0 | Systematic Assessment |
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| CHEST DISCOMFORT | General disorders | MedDRA 12.0 | Systematic Assessment |
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| OEDEMA PERIPHERAL | General disorders | MedDRA 12.0 | Systematic Assessment |
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| INFUSION SITE PAIN | General disorders | MedDRA 12.0 | Systematic Assessment |
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| INFUSION SITE WARMTH | General disorders | MedDRA 12.0 | Systematic Assessment |
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| MUCOSAL INFLAMMATION | General disorders | MedDRA 12.0 | Systematic Assessment |
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| INJECTION SITE REACTION | General disorders | MedDRA 12.0 | Systematic Assessment |
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| TUMOUR PAIN | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.0 | 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.
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| Title | Measurements |
|---|---|
|
| Grade 3-4 AEs |
|
| Discontinuation due to AEs |
|
| Title | Measurements |
|---|---|
|
| Hemoglobin |
|
| Lymphocytes (absolute) |
|
| Platelet count |
|
| Title | Measurements |
|---|---|
|
| Bilirubin |
|
| Albumin |
|
| Creatinine |
|
| Phosphorous (inorganic) |
|
| Title | Measurements |
|---|---|
|
| Sodium (serum) |
|
| Glucose (serum) |
|
| Uric acid |
|
| Title | Measurements |
|---|---|
|
| 4 hour (n=11) |
|
| 6 hour (n=13) |
|
| 8 hour (n=3) |
|
| 24 hour (n=10) |
|
| Title | Measurements |
|---|---|
|
| Total number of ECG abnormalities |
|