Leukemia, Myeloid, Acute
Conditions
Brief summary
Investigation of maximum tolerated dose, safety, efficacy and pharmcokinetics of BI 811283 in combination with cytarabine (LD-Ara-C) in previously untreated acute myeloid leukaemia (AML) patients
Interventions
DRUGBI 811283 (d 1 and 15)
BI 811283 (24 hours i.v.c.i.) on day 1 and 15 of a 4-week treatment cycle
DRUGCytarabine
Cytarabine 2 x 20 mg/d s.c. on days 1-10 of a 4-week treatment cycle
DRUGBI 811283 (d1)
BI 811283 (24 hours i.v.c.i.) on day 1 of a 4-week treatment cycle
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adult with previously untreated acute myeloid leukaemia (AML) * Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL) * Patient is considered ineligible for intensive treatment * Patient is eligible for low-dose cytarabine (LD-Ara-C) treatment * Life expectancy \> 3 months * Eastern co-operative oncology group (ECOG, R01-0787) performance score \<=2 at screening * Signed written informed consent consistent with international conference on harmonisation good clinical practice (ICH-GCP) and local legislation
Exclusion criteria
* Patient with APL (AML subtype M3 according to the French-American-British (FAB) classification). * Relapsed or treatment refractory AML. * Hypersensitivity to one of the trial drugs or the excipients. * Other malignancy requiring treatment. * Known central nervous system involvement. * Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN). * INR \> 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin). * Bilirubin greater than 1.5 mg/dl. * Serum creatinine greater than 2.0 mg/dl. * LVEF (Left ventricular ejection fraction) \< 50% in echocardiography or clinical congestive heart failure New York Heart Association (NYHA) grade III or IV. * Concomitant intercurrent illness, which would compromise the evaluation of efficacy or safety of the trial drug, e.g. active severe infection, unstable angina pectoris or cardiac arrhythmia. * Psychiatric illness or social situation that would limit compliance with trial requirements. * Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug (i.e. other chemo- or immunotherapy, see also section 4.2.2). * Contraindications for cytarabine treatment according to the summary of product characteristics (SPC). * Patients who are sexually active and unwilling to use a medically acceptable method of contraception during the trial (hormonal contraception, intrauterine device, condom with spermicide, etc.). * Pregnant or nursing female patients. * Patient unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine. | up to 28 days of treatment | The MTD was defined as the highest dose at which 6 patients were treated and less than 2 patients who experienced a dose limiting toxicities (DLT) within the first cycle of treatment.The MTD was defined based on safety data from the first cycle only. It was determined using a standard 3 + 3 design with de-escalation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | Data from first treatment administration until cut-off date of 20 October 2011; up to 1239 days | The severity and timing of AEs indicates how well the treatment regimen was tolerated. Toxicities were evaluated using the common terminology criteria for adverse events (CTCAE) grading scheme. |
| Incidence of Dose Limiting Toxicity (DLT) | up to 28 days of treatment | Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD) |
| Partial Remission | Data collected up to cut-off date 20 Oct 2011, Up to 1239 days | Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria; The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment. Partial remission (PR). All of the criteria for CR had to be met, except that the bone marrow had to contain ≥ 5% but less than 25% blasts (or ≤ 50% of initial blast count), or \< 5% blasts in the presence of Auer rods or abnormal morphology. |
| Event Free Survival (EFS) | Data collected up to cut-off date 20 Oct 2011, Up to 1239 days | EFS was defined as the duration of time from randomisation to time of treatment failure (i.e. PD), relapse from CR, or death from any cause, whichever came first. |
| Relapse Free Survival | Data collected up to cut-off date 20 Oct 2011, Up to 1239 days | Relapse-free survival was defined only for patients who achieved CR/CRi and was measured from the date of attaining CR/CRi until the date of recurrence or death from any cause, whichever occurred first. Number of patients having relapse free survival are presented. |
| Remission Duration | Data collected up to cut-off date 20 Oct 2011, Up to 1239 days | Remission duration analysis was defined only for patients who achieved CR, and was measured from the date of attaining CR until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of the cause. |
| Overall Survival (OS) | Data collected up to cut-off date 20 Oct 2011, Up to 1239 days | OS was defined for all patients that entered the trial, and measured from the date of randomization until death from any cause. |
| Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 | Cmax (maximum measured concentration of BI 811283 in plasma) during Cycle 1 |
| AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 | AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) during Cycle 1 |
| AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 | AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) during Cycle 1 |
| Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | Data collected up to cut-off date 20Oct2011, Up to 1239 days | Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria: The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment. * Complete remission (CR): morphologically leukaemia free state (i.e. bone marrow with \< 5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥ 1,000/μL and platelets \> 100,000/μL. * Complete remission with incomplete blood count recovery (incomplete CR, CRi).All of the above criteria for CR had to be met, except that neutrophils \< 1,000/μL or platelets \< 100,000/μL in the blood. |
| AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State | -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 | AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state during Cycle 1 |
| AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State | -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 | AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state during Cycle 1 |
| Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 | tmax (time from dosing to maximum measured concentration of BI 811283 in plasma) during Cycle 1 |
| Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 | tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1 |
| Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine | Cmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 |
| AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine | AUC (0-inf) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 |
| Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine | Tmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 |
| AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine | AUC (0-tz) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 |
| Pharmacodynamic Monitoring | On Day 5, i.e. 72 hours after the end of the first BI 811283 infusion, and on Day 28 in the first cycle only | Pharmacodynamic monitoring: drug effect on leukaemia cells (e.g. polyploidy, histone H3 phosphorylation, morphologic changes). An evaluation of this secondary endpoint is not possible due to missing samples / samples of poor quality of the provided material. |
| Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone | -0.05, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours | The study protocol originally included a phase II part with a treatment arm in which Cytarabine was given alone, however the sponsor discontinued the clinical development of BI 811283, therefore the protocol was amended and the reference therapy arm was removed from the study protocol -\> (Protocol Amendment 5, version 19 -May-2010, approved 28-Jun-2010). Since there was never a treatment arm in which Cytarabine was given alone; hence pharmacokinetics are not calculated. |
| Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 | Cmax (maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1 |
Countries
Germany
Participant flow
Recruitment details
68 participants were entered, and 64 were treated with the study treatment
Participants by arm
| Arm | Count |
|---|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A 5 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 4 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A 15 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 3 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A 30 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 3 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A 60 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 4 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A 100 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 7 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A 120 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 7 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B 5 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 4 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B 40 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 4 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B 80 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 5 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B 160 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 3 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B 240 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 7 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B 300 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 4 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B 360 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 3 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B 420 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection);
Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle);
BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection | 6 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Other Adverse event | 1 | 1 | 1 | 1 | 2 | 4 | 1 | 2 | 2 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Progressive disease | 3 | 2 | 2 | 2 | 4 | 4 | 3 | 2 | 3 | 2 | 4 | 3 | 2 | 4 |
| Overall Study | Reason other than those specified above | 0 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 2 |
| Overall Study | Refuse to continue medication | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 76.0 years STANDARD_DEVIATION 5.8 | 71.3 years STANDARD_DEVIATION 2.5 | 79.3 years STANDARD_DEVIATION 8.4 | 77.5 years STANDARD_DEVIATION 4 | 67.4 years STANDARD_DEVIATION 9.3 | 72.3 years STANDARD_DEVIATION 5.1 | 74.3 years STANDARD_DEVIATION 4.1 | 73.5 years STANDARD_DEVIATION 6.6 | 79.0 years STANDARD_DEVIATION 4.4 | 78.3 years STANDARD_DEVIATION 4 | 72.3 years STANDARD_DEVIATION 4.4 | 69.5 years STANDARD_DEVIATION 11.8 | 63.3 years STANDARD_DEVIATION 5.1 | 63.3 years STANDARD_DEVIATION 5.6 | 72.2 years STANDARD_DEVIATION 7.6 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 30 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 2 Participants | 3 Participants | 4 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 3 / 3 | 4 / 4 | 7 / 7 | 7 / 7 | 4 / 4 | 4 / 4 | 5 / 5 | 3 / 3 | 6 / 7 | 4 / 4 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 3 / 4 | 2 / 3 | 3 / 3 | 4 / 4 | 6 / 7 | 6 / 7 | 4 / 4 | 3 / 4 | 5 / 5 | 3 / 3 | 7 / 7 | 3 / 4 | 3 / 3 | 5 / 6 |
Outcome results
Primary
The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine.
The MTD was defined as the highest dose at which 6 patients were treated and less than 2 patients who experienced a dose limiting toxicities (DLT) within the first cycle of treatment.The MTD was defined based on safety data from the first cycle only. It was determined using a standard 3 + 3 design with de-escalation.
Time frame: up to 28 days of treatment
Population: Treated set (TS): All patients who received at least one single dose of trial medication (BI 811283 or cytarabine) were considered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Schedule A | The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine. | 100 mg |
| Treatment Schedule B | The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine. | NA mg |
Secondary
AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) during Cycle 1
Time frame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
Population: Treated set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 177 nmol·h/L | Geometric Coefficient of Variation 28.2 |
| Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 985 nmol·h/L | Geometric Coefficient of Variation 311 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 1000 nmol·h/L | Geometric Coefficient of Variation 40.7 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 2790 nmol·h/L | Geometric Coefficient of Variation 130 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 4400 nmol·h/L | Geometric Coefficient of Variation 62.9 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 5620 nmol·h/L | Geometric Coefficient of Variation 27.9 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 192 nmol·h/L | Geometric Coefficient of Variation 47.7 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 1490 nmol·h/L | Geometric Coefficient of Variation 98.1 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 2840 nmol·h/L | Geometric Coefficient of Variation 29.6 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 8870 nmol·h/L | Geometric Coefficient of Variation 59.9 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 9770 nmol·h/L | Geometric Coefficient of Variation 63 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 14100 nmol·h/L | Geometric Coefficient of Variation 32.6 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 12800 nmol·h/L | Geometric Coefficient of Variation 64.3 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 23200 nmol·h/L | Geometric Coefficient of Variation 57.9 |
Secondary
AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
AUC (0-inf) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283
Time frame: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
Population: Treated set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 104 ng·h/mL | Geometric Coefficient of Variation 31.4 |
| Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 122 ng·h/mL | Geometric Coefficient of Variation 6.89 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 102 ng·h/mL | Geometric Coefficient of Variation 31.5 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 85.4 ng·h/mL | Geometric Coefficient of Variation 35.3 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 65.9 ng·h/mL | Geometric Coefficient of Variation 42.5 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 68.1 ng·h/mL | Geometric Coefficient of Variation 41.4 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 62.0 ng·h/mL | Geometric Coefficient of Variation 24.1 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | NA ng·h/mL | — |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | NA ng·h/mL | — |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 71.2 ng·h/mL | Geometric Coefficient of Variation 20.7 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 72.7 ng·h/mL | Geometric Coefficient of Variation 23.6 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 75.5 ng·h/mL | Geometric Coefficient of Variation 27.2 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 76.9 ng·h/mL | Geometric Coefficient of Variation 19.5 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 76.8 ng·h/mL | Geometric Coefficient of Variation 42.6 |
Secondary
AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State
AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state during Cycle 1
Time frame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
Population: Treated set (Only patients with observed cases (OC) values were analysed). Steady state analyses is not applicable for Treatment Schedule B, since pharmacokinetic analyses was performed after a single dose for Treatment Schedule B.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State | 188 nmol·h/L | Geometric Coefficient of Variation 12.7 |
| Treatment Schedule B | AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State | 615 nmol·h/L | Geometric Coefficient of Variation 15.3 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State | NA nmol·h/L | — |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State | 4460 nmol·h/L | Geometric Coefficient of Variation 41.8 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State | 5140 nmol·h/L | Geometric Coefficient of Variation 105 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State | 4750 nmol·h/L | Geometric Coefficient of Variation 58.1 |
Secondary
AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) during Cycle 1
Time frame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 169 nmol·h/L | Geometric Coefficient of Variation 30.5 |
| Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 939 nmol·h/L | Geometric Coefficient of Variation 328 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 2010 nmol·h/L | Geometric Coefficient of Variation 207 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 2350 nmol·h/L | Geometric Coefficient of Variation 105 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 2810 nmol·h/L | Geometric Coefficient of Variation 135 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 5340 nmol·h/L | Geometric Coefficient of Variation 27.2 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 156 nmol·h/L | Geometric Coefficient of Variation 17.5 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 1450 nmol·h/L | Geometric Coefficient of Variation 97.3 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 2730 nmol·h/L | Geometric Coefficient of Variation 29.1 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 8680 nmol·h/L | Geometric Coefficient of Variation 60.4 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 9260 nmol·h/L | Geometric Coefficient of Variation 63.6 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 13700 nmol·h/L | Geometric Coefficient of Variation 31.7 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 12100 nmol·h/L | Geometric Coefficient of Variation 63.1 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 21700 nmol·h/L | Geometric Coefficient of Variation 55.2 |
Secondary
AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
AUC (0-tz) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283
Time frame: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 45.0 ng·h/L | Geometric Coefficient of Variation 156 |
| Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 66.9 ng·h/L | Geometric Coefficient of Variation 73.8 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 66.8 ng·h/L | Geometric Coefficient of Variation 57.6 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 71.8 ng·h/L | Geometric Coefficient of Variation 26.4 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 46.6 ng·h/L | Geometric Coefficient of Variation 51.2 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 42.3 ng·h/L | Geometric Coefficient of Variation 64.3 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 45.9 ng·h/L | Geometric Coefficient of Variation 20 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 33.9 ng·h/L | Geometric Coefficient of Variation 245 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 57.0 ng·h/L | Geometric Coefficient of Variation 18.2 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 60.2 ng·h/L | Geometric Coefficient of Variation 30.4 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 52.5 ng·h/L | Geometric Coefficient of Variation 38.8 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 52.1 ng·h/L | Geometric Coefficient of Variation 42.1 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 41.3 ng·h/L | Geometric Coefficient of Variation 87.2 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 51.6 ng·h/L | Geometric Coefficient of Variation 38.1 |
Secondary
AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State
AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state during Cycle 1
Time frame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
Population: Treated set (Only patients with observed cases (OC) values were analysed). Steady state analyses is not applicable for Treatment Schedule B, since pharmacokinetic analyses was performed after a single dose for Treatment Schedule B.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State | 183 nmol·h/L | Geometric Coefficient of Variation 14.3 |
| Treatment Schedule B | AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State | 597 nmol·h/L | Geometric Coefficient of Variation 15 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State | 1620 nmol·h/L | Geometric Coefficient of Variation 58.2 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State | 4330 nmol·h/L | Geometric Coefficient of Variation 40.5 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State | 4340 nmol·h/L | Geometric Coefficient of Variation 83.6 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State | 4820 nmol·h/L | Geometric Coefficient of Variation 55.6 |
Secondary
Cmax (Maximum Measured Concentration of BI 811283 in Plasma)
Cmax (maximum measured concentration of BI 811283 in plasma) during Cycle 1
Time frame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 8.03 nmol/L | Geometric Coefficient of Variation 32.3 |
| Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 64.10 nmol/L | Geometric Coefficient of Variation 686 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 104.00 nmol/L | Geometric Coefficient of Variation 321 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 153.00 nmol/L | Geometric Coefficient of Variation 108 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 214.00 nmol/L | Geometric Coefficient of Variation 38.8 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 272.00 nmol/L | Geometric Coefficient of Variation 30 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 7.06 nmol/L | Geometric Coefficient of Variation 10 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 66.10 nmol/L | Geometric Coefficient of Variation 85.3 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 139.00 nmol/L | Geometric Coefficient of Variation 33.8 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 499.00 nmol/L | Geometric Coefficient of Variation 101 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 445.00 nmol/L | Geometric Coefficient of Variation 71 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 631.00 nmol/L | Geometric Coefficient of Variation 31 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 528.00 nmol/L | Geometric Coefficient of Variation 40.5 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of BI 811283 in Plasma) | 1130.00 nmol/L | Geometric Coefficient of Variation 53.3 |
Secondary
Cmax (Maximum Measured Concentration of Cytarabine in Plasma)
Cmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283
Time frame: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 53.2 ng/mL | Geometric Coefficient of Variation 65.4 |
| Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 72.6 ng/mL | Geometric Coefficient of Variation 31 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 49.0 ng/mL | Geometric Coefficient of Variation 80.6 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 64.9 ng/mL | Geometric Coefficient of Variation 49.5 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 61.9 ng/mL | Geometric Coefficient of Variation 57.3 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 46.0 ng/mL | Geometric Coefficient of Variation 54.1 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 46.3 ng/mL | Geometric Coefficient of Variation 31.8 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 49.8 ng/mL | Geometric Coefficient of Variation 58.1 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 55.0 ng/mL | Geometric Coefficient of Variation 16.5 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 65.1 ng/mL | Geometric Coefficient of Variation 44.5 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 49.4 ng/mL | Geometric Coefficient of Variation 58.9 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 48.6 ng/mL | Geometric Coefficient of Variation 88.4 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 49.0 ng/mL | Geometric Coefficient of Variation 77 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Cmax (Maximum Measured Concentration of Cytarabine in Plasma) | 68.7 ng/mL | Geometric Coefficient of Variation 33.1 |
Secondary
Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State)
Cmax (maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1
Time frame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
Population: Treated set (Only patients with observed cases (OC) values were analysed). Steady state analyses is not applicable for Treatment Schedule B, since pharmacokinetic analyses was performed after a single dose for Treatment Schedule B.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 8.02 nmol/L | Geometric Coefficient of Variation 4.59 |
| Treatment Schedule B | Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 24.7 nmol/L | Geometric Coefficient of Variation 18.5 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 43.3 nmol/L | Geometric Coefficient of Variation 5.58 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 141 nmol/L | Geometric Coefficient of Variation 52.2 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 213 nmol/L | Geometric Coefficient of Variation 96.1 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 229 nmol/L | Geometric Coefficient of Variation 67.9 |
Secondary
Event Free Survival (EFS)
EFS was defined as the duration of time from randomisation to time of treatment failure (i.e. PD), relapse from CR, or death from any cause, whichever came first.
Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
Population: Treated set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | Event Free Survival (EFS) | 35.0 days | Standard Deviation 15.6 |
| Treatment Schedule B | Event Free Survival (EFS) | 122.3 days | Standard Deviation 120 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Event Free Survival (EFS) | 32.0 days | Standard Deviation 1 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Event Free Survival (EFS) | 117.5 days | Standard Deviation 102.4 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Event Free Survival (EFS) | 60.4 days | Standard Deviation 52.6 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Event Free Survival (EFS) | 62.0 days | Standard Deviation 54.1 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Event Free Survival (EFS) | 209.0 days | Standard Deviation 315.8 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Event Free Survival (EFS) | 65.0 days | Standard Deviation 41.5 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Event Free Survival (EFS) | 168.8 days | Standard Deviation 219.3 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Event Free Survival (EFS) | 62.7 days | Standard Deviation 53.9 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Event Free Survival (EFS) | 138.7 days | Standard Deviation 183.2 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Event Free Survival (EFS) | 48.5 days | Standard Deviation 36.9 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Event Free Survival (EFS) | 174.0 days | Standard Deviation 67.2 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Event Free Survival (EFS) | 30.0 days | Standard Deviation 7.3 |
Secondary
Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0)
The severity and timing of AEs indicates how well the treatment regimen was tolerated. Toxicities were evaluated using the common terminology criteria for adverse events (CTCAE) grading scheme.
Time frame: Data from first treatment administration until cut-off date of 20 October 2011; up to 1239 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 1 participants |
| Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 3 participants |
| Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 0 participants |
| Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 2 participants |
| Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 1 participants |
| Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 0 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 0 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 0 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 1 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 2 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 1 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 2 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 1 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 1 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 4 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 2 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 3 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 0 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 4 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 2 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 1 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 1 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 0 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 2 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 2 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 3 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 2 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 0 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 1 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 1 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 1 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 3 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 2 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 2 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 2 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 1 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 1 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 0 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 1 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 2 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 5 | 4 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 1 | 0 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 4 | 2 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 2 | 0 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) | CTCAE Grade 3 | 0 participants |
Secondary
Incidence of Dose Limiting Toxicity (DLT)
Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD)
Time frame: up to 28 days of treatment
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Schedule A | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Incidence of Dose Limiting Toxicity (DLT) | 2 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 1 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 1 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 1 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Incidence of Dose Limiting Toxicity (DLT) | 0 participants |
Secondary
Overall Survival (OS)
OS was defined for all patients that entered the trial, and measured from the date of randomization until death from any cause.
Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
Population: Treated set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Schedule A | Overall Survival (OS) | 122.8 days | Standard Deviation 166.2 |
| Treatment Schedule B | Overall Survival (OS) | 212.0 days | Standard Deviation 55.1 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Overall Survival (OS) | 71.3 days | Standard Deviation 40.5 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Overall Survival (OS) | 236.8 days | Standard Deviation 225.5 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Overall Survival (OS) | 148.7 days | Standard Deviation 125.5 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Overall Survival (OS) | 86.6 days | Standard Deviation 58.1 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Overall Survival (OS) | 236.8 days | Standard Deviation 322.9 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Overall Survival (OS) | 137.3 days | Standard Deviation 121.7 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Overall Survival (OS) | 198.2 days | Standard Deviation 260.1 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Overall Survival (OS) | 339.7 days | Standard Deviation 364.8 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Overall Survival (OS) | 175.7 days | Standard Deviation 175.4 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Overall Survival (OS) | 73.0 days | Standard Deviation 31.3 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Overall Survival (OS) | 294.7 days | Standard Deviation 101.5 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Overall Survival (OS) | 48.7 days | Standard Deviation 17.9 |
Secondary
Partial Remission
Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria; The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment. Partial remission (PR). All of the criteria for CR had to be met, except that the bone marrow had to contain ≥ 5% but less than 25% blasts (or ≤ 50% of initial blast count), or \< 5% blasts in the presence of Auer rods or abnormal morphology.
Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Schedule A | Partial Remission | 0 participants |
| Treatment Schedule B | Partial Remission | 0 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Partial Remission | 0 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Partial Remission | 0 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Partial Remission | 0 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Partial Remission | 0 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Partial Remission | 0 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Partial Remission | 1 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Partial Remission | 0 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Partial Remission | 0 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Partial Remission | 0 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Partial Remission | 0 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Partial Remission | 0 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Partial Remission | 0 participants |
Secondary
Pharmacodynamic Monitoring
Pharmacodynamic monitoring: drug effect on leukaemia cells (e.g. polyploidy, histone H3 phosphorylation, morphologic changes). An evaluation of this secondary endpoint is not possible due to missing samples / samples of poor quality of the provided material.
Time frame: On Day 5, i.e. 72 hours after the end of the first BI 811283 infusion, and on Day 28 in the first cycle only
Population: Treated set
Secondary
Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone
The study protocol originally included a phase II part with a treatment arm in which Cytarabine was given alone, however the sponsor discontinued the clinical development of BI 811283, therefore the protocol was amended and the reference therapy arm was removed from the study protocol -\> (Protocol Amendment 5, version 19 -May-2010, approved 28-Jun-2010). Since there was never a treatment arm in which Cytarabine was given alone; hence pharmacokinetics are not calculated.
Time frame: -0.05, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours
Population: Treated set
Secondary
Relapse Free Survival
Relapse-free survival was defined only for patients who achieved CR/CRi and was measured from the date of attaining CR/CRi until the date of recurrence or death from any cause, whichever occurred first. Number of patients having relapse free survival are presented.
Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
Population: Treated set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Relapse Free Survival | 1 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Relapse Free Survival | 1 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Relapse Free Survival | 1 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Relapse Free Survival | 1 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Relapse Free Survival | 1 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Relapse Free Survival | 1 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Relapse Free Survival | 2 participants |
Secondary
Remission Duration
Remission duration analysis was defined only for patients who achieved CR, and was measured from the date of attaining CR until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of the cause.
Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
Population: Treated set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Remission Duration | 263.0 days |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Remission Duration | 28.0 days |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Remission Duration | 337.0 days |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Remission Duration | 455.0 days |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Remission Duration | 128.0 days |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Remission Duration | 15.0 days |
Secondary
Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi])
Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria: The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment. * Complete remission (CR): morphologically leukaemia free state (i.e. bone marrow with \< 5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥ 1,000/μL and platelets \> 100,000/μL. * Complete remission with incomplete blood count recovery (incomplete CR, CRi).All of the above criteria for CR had to be met, except that neutrophils \< 1,000/μL or platelets \< 100,000/μL in the blood.
Time frame: Data collected up to cut-off date 20Oct2011, Up to 1239 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 0 participants |
| Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 0 participants |
| Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 0 participants |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 1 participants |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 0 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 1 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 1 participants |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 0 participants |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 1 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 1 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 1 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 0 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 1 participants |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 1 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CRi | 0 participants |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) | CR | 0 participants |
Secondary
Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State)
tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1
Time frame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
Population: Treated set (Only patients with observed cases (OC) values were analysed). Steady state analyses is not applicable for Treatment Schedule B, since pharmacokinetic analyses was performed after a single dose for Treatment Schedule B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Schedule A | Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 23.9 hours |
| Treatment Schedule B | Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 24.0 hours |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 6.0 hours |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 6.0 hours |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 6.0 hours |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) | 6.0 hours |
Secondary
Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma)
tmax (time from dosing to maximum measured concentration of BI 811283 in plasma) during Cycle 1
Time frame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 24.0 hours |
| Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 26.0 hours |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 25.0 hours |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 22.7 hours |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 6.0 hours |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 23.6 hours |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 23.9 hours |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 6.0 hours |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 24.1 hours |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 24.9 hours |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 6.0 hours |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 23.9 hours |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 5.9 hours |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) | 14.8 hours |
Secondary
Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma)
Tmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283
Time frame: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.50 hours |
| Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.50 hours |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.92 hours |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.83 hours |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.48 hours |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.55 hours |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.50 hours |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.50 hours |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.58 hours |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.50 hours |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.50 hours |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.50 hours |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.48 hours |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) | 0.49 hours |