Trial Outcomes & Findings for A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (NCT NCT02545283)

Last Updated: 2022-01-11

Results Overview

P53 tumor protein Wild Type (TP53 WT) population's Overall Survival was compared in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The study was terminated because of futility, therefore did not reach the planned end of the study.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

447 participants

Primary outcome timeframe

From randomization to death from any cause (up to approximately 4.5 years)

Results posted on

2022-01-11

Participant Flow

A total of 612 participants were screened, of which 447 patients were randomized as P53 tumor protein Wild Type (TP53 WT) population. TP53WT Population consists of mutation-defined Acute Myeloid Leukemia (AML) subpopulations FLT3, IDH2 and IDH1.

Participant milestones

Participant milestones
Measure	Placebo Plus Cytarabine Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Overall Study STARTED	149	298
Overall Study Received Treatment	149	292
Overall Study Safety Follow Up	149	292
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	149	298

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Plus Cytarabine Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Overall Study Lost to Follow-up	2	4
Overall Study Withdrawal by Subject	5	9
Overall Study Death	109	211
Overall Study Did not complete due to 2 ineligibilities and physician's decision	0	3
Overall Study Study Terminated By Sponsor	33	71

Baseline Characteristics

A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=298 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.	Total n=447 Participants Total of all reporting groups
Age, Continuous	59.9 Years STANDARD_DEVIATION 12.1 • n=5 Participants	59.4 Years STANDARD_DEVIATION 13.1 • n=7 Participants	59.6 Years STANDARD_DEVIATION 12.8 • n=5 Participants
Sex/Gender, Customized Male	86 Participants n=5 Participants	163 Participants n=7 Participants	249 Participants n=5 Participants
Sex/Gender, Customized Female	63 Participants n=5 Participants	135 Participants n=7 Participants	198 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	112 Participants n=5 Participants	231 Participants n=7 Participants	343 Participants n=5 Participants
Race/Ethnicity, Customized Not Stated	18 Participants n=5 Participants	36 Participants n=7 Participants	54 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	25 Participants n=5 Participants	51 Participants n=7 Participants	76 Participants n=5 Participants
Race/Ethnicity, Customized Asian	11 Participants n=5 Participants	20 Participants n=7 Participants	31 Participants n=5 Participants
Race/Ethnicity, Customized Black or African America	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	111 Participants n=5 Participants	222 Participants n=7 Participants	333 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to death from any cause (up to approximately 4.5 years)

Population: TP53-WT ITT Population

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=123 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=232 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Overall Survival in TP53 WT Population	9.13 Months Interval 7.59 to 10.64	8.28 Months Interval 6.67 to 10.87

SECONDARY outcome

Timeframe: At the end of induction (up to Day 56)

Population: TP53-WT ITT Population

Rate of complete response at the end of induction in the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The design followed a hierarchical statistical testing framework.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=123 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=232 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Percentage of Participants in Complete Response (CR) at the End of Induction According to Hematologic Malignancy Response Assessment (HMRA) in TP53 WT Population	20.3 Percentage of Participants	17.1 Percentage of Participants

SECONDARY outcome

Timeframe: From randomization up to treatment failure, relapse, or death from any cause (up to approximately 4.5 years)

Population: TP53-WT ITT Population

Event Free Survival (EFS) is defined as the time from the date of randomization to whichever occurs first: treatment failure (failure to achieve CR, set as day of final response assessment), relapse from CR, or death from any cause. The study was terminated because of futility, therefore did not reach the planned end of the study. The design followed a hierarchical statistical testing framework.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=123 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=232 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Event-Free Survival (EFS) According to HMRA in TP53 WT Population	6.29 Weeks Interval 5.86 to 8.0	4.36 Weeks Interval 4.14 to 5.0

SECONDARY outcome

Timeframe: At the end of induction (up to Day 56)

Population: TP53-WT ITT Population

Rate of overall remission (complete remission, complete remission with incomplete hematologic recovery, complete remission with incomplete platelet count recovery) at the end of induction in the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The design followed a hierarchical statistical testing framework.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=123 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=232 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Percentage of Participants With Overall Remission (CR, CRp, and CRi) at the End of Induction According to HMRA in TP53 WT Population	38.8 Percentage of Participants	22.0 Percentage of Participants

SECONDARY outcome

Timeframe: From achieving CR until relapse or death from any cause (up to approximately 4.5 years)

Population: TP53-WT Population. The number analyzed includes participants who were evaluable at each timepoint.

DOR is defined for patients achieving complete remission and is the time from clinical remission until relapse or death from any cause, whichever occurs first. For patients with none of these events before time of analysis, DOR is censored at the date of the patient's last response assessment. The Median upper limits were set to 999 because they were not reached and therefore it was Not Evaluable (NE) and the field is numeric only. The study was terminated because of futility, therefore did not reach the planned end of the study.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=25 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=59 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Duration of Remission Following CR (DOR) in TP53 WT Population	18.73 Months Interval 5.26 to Insufficient number of participants with events	16.76 Months Interval 7.82 to Insufficient number of participants with events

SECONDARY outcome

Timeframe: Baseline up to approximately 4.5 years

Population: TP53-WT ITT Population

Rate of complete response at the end of induction in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2, respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The study was terminated because of futility, therefore did not reach the planned end of the study.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=123 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=232 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Percentage of Participants Undergoing HSCT Following Complete Response (CR), in TP53 WT Population	10.6 Percentage of Participants	11.6 Percentage of Participants

SECONDARY outcome

Timeframe: At the end of induction (up to Day 56)

Population: TP53-WT Population. The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=123 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=232 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Percentage of Participants With Complete Response (CR) in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population FLT3	12.5 Percentage of Participants	15.3 Percentage of Participants
Percentage of Participants With Complete Response (CR) in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population IDH1	11.1 Percentage of Participants	34.8 Percentage of Participants
Percentage of Participants With Complete Response (CR) in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population IDH2	23.1 Percentage of Participants	29.5 Percentage of Participants

SECONDARY outcome

Timeframe: From randomization to death from any cause (up to approximately 4.5 years)

Population: TP53-WT ITT Population. The number analyzed includes participants who were evaluable at each timepoint.

Overall survival in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2 respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The Median upper limits were set to 999 because they were not reached and therefore it was Not Evaluable (NE) and the field is numeric only. The study was terminated because of futility, therefore did not reach the planned end of the study.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=123 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=232 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Overall Survival in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population IDH2	11.37 Months Interval 8.02 to Insufficient number of participants with events	11.01 Months Interval 6.87 to Insufficient number of participants with events
Overall Survival in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population IDH1	9.13 Months Interval 2.5 to 16.69	8.25 Months Interval 4.27 to 37.29
Overall Survival in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population FLT3	4.76 Months Interval 1.97 to 13.04	5.55 Months Interval 4.5 to 8.25

SECONDARY outcome

Timeframe: Baseline up to approximately 4.5 years

Population: Safety-Evaluable Population

Participants who experienced at least one Adverse Event by severity, According to National Cancer Institute common terminology criteria for Adverse Events, version 4.03 (NCI-CTCAE v4.03) have been reported. The study was terminated because of futility, therefore did not reach the planned end of the study.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Number of Participants Who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03)	149 Participants	232 Participants

SECONDARY outcome

Timeframe: Baseline up to approximately 4.5 years

Population: Safety Population

Participants with Adverse Events leading to discontinuation of the study have been reported. The study was terminated because of futility, therefore did not reach the planned end of the study.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Number of Participants With Adverse Events Leading to Discontinuation	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 30

Population: Safety Population

The number of participants with AE resulted by death within 30 days from dosing is reported

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Number of Participants With Adverse Events Leading to Death up to Day 30	9 Participants	23 Participants

SECONDARY outcome

Timeframe: Up to Day 60

Population: Safety Population

The number of participants with AE resulted by death within 60 days from dosing is reported

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Number of Participants With Adverse Events Leading to Death up to Day 60	24 Participants	60 Participants

SECONDARY outcome

Timeframe: Up to Approximately 4.5 Years

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Laboratory parameters for blood biochemistry will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment. For each patient, baseline is the last observation prior to initiation of study drug. For each laboratory test, patients with at least 1 post-baseline assessment are included in the analysis. For each cell, the denominator is the number of patients with baseline NCI-CTCAE Grade 0-2 in the specified direction of abnormality, or Grade 1-4 in the opposite direction of abnormality.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Albumin Low	8 Participants	22 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Alkaline Phosphatase High	2 Participants	9 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 SGPT/ALT High	13 Participants	16 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 SGOT/AST High	9 Participants	13 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Calcium Low	8 Participants	36 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Creatinine High	4 Participants	11 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Glucose Low	1 Participants	0 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Glucose High	9 Participants	25 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Magnesium Low	0 Participants	8 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Magnesium High	5 Participants	10 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Phosphorus Low	18 Participants	72 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Potassium High	5 Participants	8 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Sodium Low	6 Participants	17 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Sodium High	1 Participants	7 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Bilirubin High	9 Participants	42 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Uric Acid High	29 Participants	53 Participants
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Potassium Low	21 Participants	76 Participants

SECONDARY outcome

Timeframe: Up to Approximately 4.5 Years

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Laboratory parameters for hematology will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment. For each patient, baseline is the last observation prior to initiation of study drug. For each laboratory test, patients with at least 1 post-baseline assessment are included in the analysis. For each cell, the denominator is the number of patients with baseline NCI-CTCAE Grade 0-2 in the specified direction of abnormality, or Grade 1-4 in the opposite direction of abnormality.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Hemoglobin Low	83 Participants	191 Participants
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Hemoglobin High	1 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Lymphocytes Abs Low	109 Participants	229 Participants
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Lymphocytes Abs High	1 Participants	1 Participants
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Neutrophils, Total, Abs Low	40 Participants	97 Participants
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Platelet Low	59 Participants	128 Participants
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Total Leukocyte Count Low	87 Participants	184 Participants
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 Total Leukocyte Count High	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Change From Baseline in Body Temperature Over Time Cycle 1 Day 28	0.06 C, Celsius Degree Standard Deviation 0.65	0.23 C, Celsius Degree Standard Deviation 0.87
Change From Baseline in Body Temperature Over Time Cycle 1 Day 29-42	0.08 C, Celsius Degree Standard Deviation 0.69	0.00 C, Celsius Degree Standard Deviation 0.71
Change From Baseline in Body Temperature Over Time Cycle 1 Day 43-56	-0.02 C, Celsius Degree Standard Deviation 0.53	0.07 C, Celsius Degree Standard Deviation 0.80
Change From Baseline in Body Temperature Over Time Baseline	36.49 C, Celsius Degree Standard Deviation 0.59	36.52 C, Celsius Degree Standard Deviation 0.51
Change From Baseline in Body Temperature Over Time Cycle 1 Day 8	0.07 C, Celsius Degree Standard Deviation 0.82	0.32 C, Celsius Degree Standard Deviation 0.72
Change From Baseline in Body Temperature Over Time Cycle 1 Day 15	0.30 C, Celsius Degree Standard Deviation 0.91	0.46 C, Celsius Degree Standard Deviation 0.92
Change From Baseline in Body Temperature Over Time Cycle 1 Day 22	0.22 C, Celsius Degree Standard Deviation 0.74	0.36 C, Celsius Degree Standard Deviation 0.86
Change From Baseline in Body Temperature Over Time Cycle 2 Day 1	0.11 C, Celsius Degree Standard Deviation 0.60	-0.10 C, Celsius Degree Standard Deviation 0.47
Change From Baseline in Body Temperature Over Time Cycle 2 Day 8	-0.08 C, Celsius Degree Standard Deviation 0.51	0.07 C, Celsius Degree Standard Deviation 0.56
Change From Baseline in Body Temperature Over Time Cycle 2 Day 15	0.17 C, Celsius Degree Standard Deviation 0.76	0.34 C, Celsius Degree Standard Deviation 0.83
Change From Baseline in Body Temperature Over Time Cycle 2 Day 22	0.04 C, Celsius Degree Standard Deviation 0.72	0.10 C, Celsius Degree Standard Deviation 0.59
Change From Baseline in Body Temperature Over Time Cycle 2 Day 28	-0.22 C, Celsius Degree Standard Deviation 0.65	0.04 C, Celsius Degree Standard Deviation 0.62
Change From Baseline in Body Temperature Over Time Cycle 2 Day 29-56	-0.06 C, Celsius Degree Standard Deviation 0.36	-0.09 C, Celsius Degree Standard Deviation 0.55
Change From Baseline in Body Temperature Over Time Cycle 3 Day 1	-0.25 C, Celsius Degree Standard Deviation 0.54	-0.19 C, Celsius Degree Standard Deviation 0.51
Change From Baseline in Body Temperature Over Time Cycle 3 Day 8	0.10 C, Celsius Degree Standard Deviation 0.60	-0.04 C, Celsius Degree Standard Deviation 0.59
Change From Baseline in Body Temperature Over Time Cycle 3 Day 15	-0.09 C, Celsius Degree Standard Deviation 0.76	0.29 C, Celsius Degree Standard Deviation 0.65
Change From Baseline in Body Temperature Over Time Cycle 3 Day 22	-0.07 C, Celsius Degree Standard Deviation 0.64	0.04 C, Celsius Degree Standard Deviation 0.49
Change From Baseline in Body Temperature Over Time Cycle 3 Day 28	-0.26 C, Celsius Degree Standard Deviation 0.63	-0.15 C, Celsius Degree Standard Deviation 0.52
Change From Baseline in Body Temperature Over Time Cycle 3 Day 29-56	0.27 C, Celsius Degree Standard Deviation 0.47	-0.25 C, Celsius Degree Standard Deviation 0.52

SECONDARY outcome

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

SECONDARY outcome

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

SECONDARY outcome

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Change From Baseline in Pulse Rate Over Time Baseline	78.4 Beats per Minute Standard Deviation 14.4	79.2 Beats per Minute Standard Deviation 12.9
Change From Baseline in Pulse Rate Over Time Cycle 1 Day 8	-4.3 Beats per Minute Standard Deviation 15.9	3.4 Beats per Minute Standard Deviation 15.6
Change From Baseline in Pulse Rate Over Time Cycle 1 Day 15	1.5 Beats per Minute Standard Deviation 16.0	1.1 Beats per Minute Standard Deviation 17.2
Change From Baseline in Pulse Rate Over Time Cycle 1 Day 22	0.2 Beats per Minute Standard Deviation 16.2	4.1 Beats per Minute Standard Deviation 15.8
Change From Baseline in Pulse Rate Over Time Cycle 1 Day 28	4.8 Beats per Minute Standard Deviation 15.8	4.0 Beats per Minute Standard Deviation 16.8
Change From Baseline in Pulse Rate Over Time Cycle 1 Day 29-42	2.0 Beats per Minute Standard Deviation 13.5	5.1 Beats per Minute Standard Deviation 16.4
Change From Baseline in Pulse Rate Over Time Cycle 1 Day 43-56	5.5 Beats per Minute Standard Deviation 18.6	6.8 Beats per Minute Standard Deviation 14.0
Change From Baseline in Pulse Rate Over Time Cycle 2 Day 1	2.0 Beats per Minute Standard Deviation 16.6	-0.9 Beats per Minute Standard Deviation 12.0
Change From Baseline in Pulse Rate Over Time Cycle 2 Day 8	-3.3 Beats per Minute Standard Deviation 18.6	2.4 Beats per Minute Standard Deviation 14.9
Change From Baseline in Pulse Rate Over Time Cycle 2 Day 15	-0.4 Beats per Minute Standard Deviation 12.7	1.7 Beats per Minute Standard Deviation 18.4
Change From Baseline in Pulse Rate Over Time Cycle 2 Day 22	2.3 Beats per Minute Standard Deviation 15.5	0.3 Beats per Minute Standard Deviation 15.4
Change From Baseline in Pulse Rate Over Time Cycle 2 Day 28	-2.3 Beats per Minute Standard Deviation 14.6	1.2 Beats per Minute Standard Deviation 12.2
Change From Baseline in Pulse Rate Over Time Cycle 2 Day 29-56	1.8 Beats per Minute Standard Deviation 11.8	4.0 Beats per Minute Standard Deviation 14.8
Change From Baseline in Pulse Rate Over Time Cycle 3 Day 1	0.4 Beats per Minute Standard Deviation 18.4	1.0 Beats per Minute Standard Deviation 9.8
Change From Baseline in Pulse Rate Over Time Cycle 3 Day 8	1.3 Beats per Minute Standard Deviation 21.5	2.4 Beats per Minute Standard Deviation 16.2
Change From Baseline in Pulse Rate Over Time Cycle 3 Day 15	2.5 Beats per Minute Standard Deviation 16.9	1.9 Beats per Minute Standard Deviation 11.9
Change From Baseline in Pulse Rate Over Time Cycle 3 Day 22	4.8 Beats per Minute Standard Deviation 19.7	3.4 Beats per Minute Standard Deviation 13.6
Change From Baseline in Pulse Rate Over Time Cycle 3 Day 28	0.4 Beats per Minute Standard Deviation 16.1	0.9 Beats per Minute Standard Deviation 13.7
Change From Baseline in Pulse Rate Over Time Cycle 3 Day 29-56	-5.0 Beats per Minute Standard Deviation 1.7	5.2 Beats per Minute Standard Deviation 11.5

SECONDARY outcome

Timeframe: Up to Approximately 4.5 Years

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

SECONDARY outcome

Timeframe: Baseline; Cycles 1-3 Day 1 (2 hrs pre-dose, post-Cytarabine and 6 hrs post-Idasanutlin/Placebo ); Cycle 1-3 Day 2; Cycle 1 Day 5 (within 2 hrs Idanasanutlin/Placebo, post-Cytarabine and 6 hrs post-Idasanutlin/Placebo), Study Drug Completion

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Baseline	77.3 Beats per Minute Standard Deviation 13.2	78.6 Beats per Minute Standard Deviation 14.2
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 1 Day 1 2 Hours Pre-dose	1.1 Beats per Minute Standard Deviation 11.6	-0.8 Beats per Minute Standard Deviation 11.7
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 1 Day 1 Post-Cytarabine	-0.1 Beats per Minute Standard Deviation 8.4	-0.4 Beats per Minute Standard Deviation 9.8
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo	0.1 Beats per Minute Standard Deviation 9.6	1.4 Beats per Minute Standard Deviation 9.2
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 1 Day 2	-2.2 Beats per Minute Standard Deviation 11.0	-0.4 Beats per Minute Standard Deviation 11.7
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo	-10.3 Beats per Minute Standard Deviation 14.4	-1.2 Beats per Minute Standard Deviation 14.3
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 1 Day 5 - Post-Cytarabine	-9.9 Beats per Minute Standard Deviation 12.8	-3.0 Beats per Minute Standard Deviation 14.2
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo	-10.7 Beats per Minute Standard Deviation 13.2	-3.1 Beats per Minute Standard Deviation 14.0
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo	-0.5 Beats per Minute Standard Deviation 13.5	-4.8 Beats per Minute Standard Deviation 12.0
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 2 Day 1 Post-Cytarabine	0.8 Beats per Minute Standard Deviation 17.3	-4.8 Beats per Minute Standard Deviation 12.6
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo	-0.7 Beats per Minute Standard Deviation 16.6	-0.7 Beats per Minute Standard Deviation 15.6
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 2 Day 2	-5.2 Beats per Minute Standard Deviation 15.7	-4.8 Beats per Minute Standard Deviation 10.3
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo	-3.0 Beats per Minute Standard Deviation 14.2	-7.1 Beats per Minute Standard Deviation 10.2
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 3 Day 1 Post-Cytarabine	-8.9 Beats per Minute Standard Deviation 21.0	-4.5 Beats per Minute Standard Deviation 7.4
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo	-2.0 Beats per Minute Standard Deviation 17.2	-0.1 Beats per Minute Standard Deviation 15.0
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Cycle 3 Day 2	0.1 Beats per Minute Standard Deviation 14.7	-9.3 Beats per Minute Standard Deviation 8.8
Change From Baseline in Heart Rate, as Measured by Electrocardiogram Study Drug Completion/Discontinuation	3.4 Beats per Minute Standard Deviation 15.9	4.5 Beats per Minute Standard Deviation 16.4

SECONDARY outcome

Timeframe: Baseline, Days 1, 2, and 5 of Cycle 1, Days 1, 2 of Cycles 2 and 3 (1 cycle is 28 days), Treatment Discontinuation Visit (28 days after last dose of study drug)

Population: Safety Population. The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

SECONDARY outcome

Timeframe: Up to 3 cycles (1 cycle is 28 days)

Population: ITT Population

Participants were planned to be treated up to 3 Cycles.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Total Duration of Study Treatment	16.5 Days Standard Deviation 28.29	17.6 Days Standard Deviation 28.25

SECONDARY outcome

Timeframe: Up to 3 cycles (1 cycle is 28 days)

Population: Safety Population

Participants who started the study treatment cycles are reported.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Number of Treatment Cycles Started	1.3 Treatment Cycles Standard Deviation 0.63	1.2 Treatment Cycles Standard Deviation 0.54

SECONDARY outcome

Timeframe: Up to 3 cycles (1 cycle is 28 days)

Population: Safety Population. Participants did not receive Idasanutlin in the "Placebo Plus Cytarabine" Arm, so this data were not collected.

The cumulative doses of idasanutlin and cytaradine are reported.

Outcome measures

Outcome measures
Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Cumulative Dose of Idasanutlin and Cytarabine Idasanutlin/Placebo cumulative dose (mg)	—	3340.1 Milligram (mg) Standard Deviation 896.35
Cumulative Dose of Idasanutlin and Cytarabine Cytarabine cumulative dose (mg)	11500 Milligram (mg) Standard Deviation 5850	11200 Milligram (mg) Standard Deviation 5190

SECONDARY outcome

Timeframe: Cycle 1: Predose (0 hour [Hr]), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)

Population: Due to futility the planned participant enrollment was observed, therefore result data were not collected.

Apparent Clearance (CL/F) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. The planned CL/F did not derive for the result data and was not reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

Apparent Volume of Distribution (Vd/F) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

Maximum Concentration Observed (Cmax) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

Steady-State Concentration (Ctrough) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

Area Under the Concentration-Time Curve (AUC) During One Dosing Interval (AUCtau) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

AUC from Time Zero to 24 Hours Post Dose (AUC0-24) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

Half-Life (t 1/2) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1: Within 2 Hr pre-cytarabine dose, end of 1-3 Hr cytarabine infusion, 6 Hr post idasanutlin morning dose on Days 1, 5; Within 2 Hr pre-cytarabine dose on Day 2; Cycle 2, 3: Within 2 Hr pre-cytarabine dose on Day 2 (Cycle length= 28 days)

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

The Total Clearance (CL) of Cytarabine was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

The Volume of Distribution (Vd) of Cytarabine was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), Days 8, 15, 28 of Cycle 1, Days 1, 8, 15, 28 of Cycles 2, 3, 28 days after last dose (last dose on Cycle 3 Day 5), thereafter every 3 months until relapse (maximum up to 3.5 years)

Population: Due to insufficient participant compliance rate, an insufficient enrollment was observed and result data were not collected.

The compliance rate (defined as the number of patients who completed as least 1 question on the measure) at baseline was 56% and 61% for the Idasanutlin arm and the placebo arm, respectively. This compliance rate remained the same post-baseline in both arms. Due to the low compliance rates in both arms during the entire treatment period, the planned analyses were not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected.

The compliance rate (defined as the number of patients who completed as least 1 question on the measure) at baseline was 56% and 61% for the Idasanutlin arm and the placebo arm, respectively. Compliance remained the same post-baseline in both arms Due to the low compliance rates in both arms during the entire treatment period, the planned analyses were not performed.

Outcome measures

Outcome data not reported

Adverse Events

Idasanutlin-Cytarabine

Serious events: 173 serious events

Other events: 290 other events

Deaths: 211 deaths

Placebo-Cytarabine

Serious events: 72 serious events

Other events: 147 other events

Deaths: 109 deaths

Serious adverse events

Other adverse events

Additional Information

Reference Study ID Number: WO29519

www.roche.com/about_roche/roche_worldwide.htm

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Change From Baseline in Systolic Blood Pressure Over Time Baseline	120.6 Millimeters of mercury (mmHg) Standard Deviation 17.2	122.1 Millimeters of mercury (mmHg) Standard Deviation 16.2
Change From Baseline in Systolic Blood Pressure Over Time Cycle 1 Day 8	-3.7 Millimeters of mercury (mmHg) Standard Deviation 20.0	-6.9 Millimeters of mercury (mmHg) Standard Deviation 18.6
Change From Baseline in Systolic Blood Pressure Over Time Cycle 1 Day 15	-2.8 Millimeters of mercury (mmHg) Standard Deviation 19.2	-0.1 Millimeters of mercury (mmHg) Standard Deviation 18.7
Change From Baseline in Systolic Blood Pressure Over Time Cycle 1 Day 22	0.7 Millimeters of mercury (mmHg) Standard Deviation 20.3	-1.5 Millimeters of mercury (mmHg) Standard Deviation 19.6
Change From Baseline in Systolic Blood Pressure Over Time Cycle 1 Day 28	1.2 Millimeters of mercury (mmHg) Standard Deviation 21.7	-0.5 Millimeters of mercury (mmHg) Standard Deviation 17.6
Change From Baseline in Systolic Blood Pressure Over Time Cycle 1 Day 29-42	4.4 Millimeters of mercury (mmHg) Standard Deviation 17.8	3.4 Millimeters of mercury (mmHg) Standard Deviation 17.7
Change From Baseline in Systolic Blood Pressure Over Time Cycle 1 Day 43-56	9.8 Millimeters of mercury (mmHg) Standard Deviation 17.4	3.8 Millimeters of mercury (mmHg) Standard Deviation 20.9
Change From Baseline in Systolic Blood Pressure Over Time Cycle 2 Day 1	6.9 Millimeters of mercury (mmHg) Standard Deviation 15.6	0.6 Millimeters of mercury (mmHg) Standard Deviation 15.2
Change From Baseline in Systolic Blood Pressure Over Time Cycle 2 Day 8	5.3 Millimeters of mercury (mmHg) Standard Deviation 18.6	-5.1 Millimeters of mercury (mmHg) Standard Deviation 16.2
Change From Baseline in Systolic Blood Pressure Over Time Cycle 2 Day 15	-1.7 Millimeters of mercury (mmHg) Standard Deviation 17.7	-0.2 Millimeters of mercury (mmHg) Standard Deviation 19.6
Change From Baseline in Systolic Blood Pressure Over Time Cycle 2 Day 22	5.5 Millimeters of mercury (mmHg) Standard Deviation 19.8	2.5 Millimeters of mercury (mmHg) Standard Deviation 17.0
Change From Baseline in Systolic Blood Pressure Over Time Cycle 2 Day 28	5.8 Millimeters of mercury (mmHg) Standard Deviation 22.2	5.0 Millimeters of mercury (mmHg) Standard Deviation 17.9
Change From Baseline in Systolic Blood Pressure Over Time Cycle 2 Day 29-56	-1.0 Millimeters of mercury (mmHg) Standard Deviation 18.2	6.6 Millimeters of mercury (mmHg) Standard Deviation 16.3
Change From Baseline in Systolic Blood Pressure Over Time Cycle 3 Day 1	11.2 Millimeters of mercury (mmHg) Standard Deviation 18.9	2.3 Millimeters of mercury (mmHg) Standard Deviation 18.2
Change From Baseline in Systolic Blood Pressure Over Time Cycle 3 Day 8	6.0 Millimeters of mercury (mmHg) Standard Deviation 23.5	-1.7 Millimeters of mercury (mmHg) Standard Deviation 13.4
Change From Baseline in Systolic Blood Pressure Over Time Cycle 3 Day 15	3.3 Millimeters of mercury (mmHg) Standard Deviation 22.5	0.2 Millimeters of mercury (mmHg) Standard Deviation 21.7
Change From Baseline in Systolic Blood Pressure Over Time Cycle 3 Day 22	13.9 Millimeters of mercury (mmHg) Standard Deviation 22.8	-1.1 Millimeters of mercury (mmHg) Standard Deviation 17.7
Change From Baseline in Systolic Blood Pressure Over Time Cycle 3 Day 28	5.3 Millimeters of mercury (mmHg) Standard Deviation 23.0	7.1 Millimeters of mercury (mmHg) Standard Deviation 18.0
Change From Baseline in Systolic Blood Pressure Over Time Cycle 3 Day 29-56	27.7 Millimeters of mercury (mmHg) Standard Deviation 28.3	5.1 Millimeters of mercury (mmHg) Standard Deviation 18.4

Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Change From Baseline in Diastolic Blood Pressure Over Time Baseline	70.2 Millimeters of mercury (mmHg) Standard Deviation 9.9	71.5 Millimeters of mercury (mmHg) Standard Deviation 10.6
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 1 Day 8	-1.5 Millimeters of mercury (mmHg) Standard Deviation 12.6	-3.1 Millimeters of mercury (mmHg) Standard Deviation 12.7
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 1 Day 15	-1.3 Millimeters of mercury (mmHg) Standard Deviation 11.3	-1.3 Millimeters of mercury (mmHg) Standard Deviation 12.3
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 1 Day 22	-0.5 Millimeters of mercury (mmHg) Standard Deviation 11.1	-1.4 Millimeters of mercury (mmHg) Standard Deviation 12.9
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 1 Day 28	1.0 Millimeters of mercury (mmHg) Standard Deviation 13.2	-0.7 Millimeters of mercury (mmHg) Standard Deviation 12.6
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 1 Day 29-42	3.8 Millimeters of mercury (mmHg) Standard Deviation 10.5	0.6 Millimeters of mercury (mmHg) Standard Deviation 12.4
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 1 Day 43-56	1.7 Millimeters of mercury (mmHg) Standard Deviation 11.8	0.9 Millimeters of mercury (mmHg) Standard Deviation 13.5
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 2 Day 1	1.1 Millimeters of mercury (mmHg) Standard Deviation 13.5	0.9 Millimeters of mercury (mmHg) Standard Deviation 12.9
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 2 Day 8	0.4 Millimeters of mercury (mmHg) Standard Deviation 13.5	-2.2 Millimeters of mercury (mmHg) Standard Deviation 13.2
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 2 Day 15	-0.6 Millimeters of mercury (mmHg) Standard Deviation 14.8	-1.5 Millimeters of mercury (mmHg) Standard Deviation 15.4
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 2 Day 22	3.1 Millimeters of mercury (mmHg) Standard Deviation 11.6	1.7 Millimeters of mercury (mmHg) Standard Deviation 11.3
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 2 Day 28	4.6 Millimeters of mercury (mmHg) Standard Deviation 13.9	3.9 Millimeters of mercury (mmHg) Standard Deviation 12.7
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 2 Day 29-56	-2.9 Millimeters of mercury (mmHg) Standard Deviation 12.4	3.2 Millimeters of mercury (mmHg) Standard Deviation 15.8
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 3 Day 1	5.0 Millimeters of mercury (mmHg) Standard Deviation 8.4	0.3 Millimeters of mercury (mmHg) Standard Deviation 10.7
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 3 Day 8	2.0 Millimeters of mercury (mmHg) Standard Deviation 15.5	-3.3 Millimeters of mercury (mmHg) Standard Deviation 11.8
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 3 Day 15	0.7 Millimeters of mercury (mmHg) Standard Deviation 11.1	-1.8 Millimeters of mercury (mmHg) Standard Deviation 11.1
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 3 Day 22	10.1 Millimeters of mercury (mmHg) Standard Deviation 14.3	-2.1 Millimeters of mercury (mmHg) Standard Deviation 9.3
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 3 Day 28	2.3 Millimeters of mercury (mmHg) Standard Deviation 14.7	1.3 Millimeters of mercury (mmHg) Standard Deviation 10.1
Change From Baseline in Diastolic Blood Pressure Over Time Cycle 3 Day 29-56	5.0 Millimeters of mercury (mmHg) Standard Deviation 21.8	2.6 Millimeters of mercury (mmHg) Standard Deviation 13.6

Measure	Placebo Plus Cytarabine n=149 Participants Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.	Idasanutlin Plus Cytarabine n=292 Participants Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.
Change From Baseline in Respiratory Rate Over Time Baseline	16.3 Breaths per Minute Standard Deviation 2.7	16.6 Breaths per Minute Standard Deviation 2.7
Change From Baseline in Respiratory Rate Over Time Cycle 1 Day 8	-0.1 Breaths per Minute Standard Deviation 2.7	0.0 Breaths per Minute Standard Deviation 2.8
Change From Baseline in Respiratory Rate Over Time Cycle 1 Day 15	0.7 Breaths per Minute Standard Deviation 2.9	0.4 Breaths per Minute Standard Deviation 2.8
Change From Baseline in Respiratory Rate Over Time Cycle 1 Day 22	0.6 Breaths per Minute Standard Deviation 3.2	0.7 Breaths per Minute Standard Deviation 4.1
Change From Baseline in Respiratory Rate Over Time Cycle 1 Day 28	0.4 Breaths per Minute Standard Deviation 2.9	0.6 Breaths per Minute Standard Deviation 2.9
Change From Baseline in Respiratory Rate Over Time Cycle 1 Day 29-42	0.7 Breaths per Minute Standard Deviation 2.1	0.5 Breaths per Minute Standard Deviation 2.7
Change From Baseline in Respiratory Rate Over Time Cycle 1 Day 43-56	0.3 Breaths per Minute Standard Deviation 1.0	0.0 Breaths per Minute Standard Deviation 2.9
Change From Baseline in Respiratory Rate Over Time Cycle 2 Day 1	-0.3 Breaths per Minute Standard Deviation 2.8	-0.2 Breaths per Minute Standard Deviation 3.2
Change From Baseline in Respiratory Rate Over Time Cycle 2 Day 8	-0.2 Breaths per Minute Standard Deviation 2.9	0.1 Breaths per Minute Standard Deviation 3.3
Change From Baseline in Respiratory Rate Over Time Cycle 2 Day 15	0.5 Breaths per Minute Standard Deviation 2.4	0.0 Breaths per Minute Standard Deviation 2.5
Change From Baseline in Respiratory Rate Over Time Cycle 2 Day 22	0.8 Breaths per Minute Standard Deviation 2.3	0.4 Breaths per Minute Standard Deviation 1.4
Change From Baseline in Respiratory Rate Over Time Cycle 2 Day 28	-0.3 Breaths per Minute Standard Deviation 2.3	0.5 Breaths per Minute Standard Deviation 3.5
Change From Baseline in Respiratory Rate Over Time Cycle 2 Day 29-56	0.2 Breaths per Minute Standard Deviation 1.8	0.3 Breaths per Minute Standard Deviation 2.5
Change From Baseline in Respiratory Rate Over Time Cycle 3 Day 1	1.1 Breaths per Minute Standard Deviation 2.5	0.2 Breaths per Minute Standard Deviation 2.1
Change From Baseline in Respiratory Rate Over Time Cycle 3 Day 8	0.2 Breaths per Minute Standard Deviation 2.5	-1.0 Breaths per Minute Standard Deviation 3.1
Change From Baseline in Respiratory Rate Over Time Cycle 3 Day 15	1.5 Breaths per Minute Standard Deviation 3.6	0.9 Breaths per Minute Standard Deviation 2.2
Change From Baseline in Respiratory Rate Over Time Cycle 3 Day 22	1.1 Breaths per Minute Standard Deviation 2.7	0.8 Breaths per Minute Standard Deviation 1.6
Change From Baseline in Respiratory Rate Over Time Cycle 3 Day 28	0.3 Breaths per Minute Standard Deviation 1.2	0.8 Breaths per Minute Standard Deviation 1.8
Change From Baseline in Respiratory Rate Over Time Cycle 3 Day 29-56	0.7 Breaths per Minute Standard Deviation 4.6	0.1 Breaths per Minute Standard Deviation 2.4