Randomized Study of CX-01 Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia

• Sponsor: Chimerix (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02873338
• Collaborator: (none)
• Enrollment: 75
• Locations: 23
• Arms: 3
• Actual Duration (Months): 34
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was an exploratory Phase 2, open label, randomized, multicenter , parallel group study to determine whether there was evidence that the addition of dociparstat (CX-01) at 2 different does levels to standard induction therapy (cytarabine+idarubicin, "7+3") and consolidation therapy had an additive therapeutic effect for subjects newly diagnosed with acute myeloid leukemia (AML) when compared with subjects receiving standard induction chemotherapy alone.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: CX-01; Drug: Idarubicin; Drug: Cytarabine	Phase 2

Detailed Description

This was an exploratory Phase 2, open label, randomized, multicenter , parallel group study to determine whether there was evidence that the addition of dociparstat (CX-01) at 2 different does levels to standard induction therapy (cytarabine+idarubicin, "7+3") and consolidation therapy had an additive therapeutic effect for subjects newly diagnosed with acute myeloid leukemia (AML) when compared with subjects receiving standard induction chemotherapy alone.

Approximately 75 subjects were to be randomized in a 1:1:1 ratio to 1 of the following treatment groups:

• Group 1: cytarabine+idarubicin

• Group 2: cytarabine+idarubicin + dociparstat 0.125 mg/kg/h

• Group 3: cytarabine+idarubicin + dociparstat 0.25 mg/kg/h

Subjects received up to 2 induction cycles and up to 2 consolidation cycles and participated in the study for up to 18 months. Clinical laboratory tests were conducted routinely, and bone marrow aspirates and biopsies were performed during the induction cycles. Safety was monitored through adverse events and clinical laboratory results.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Phase II Study of CX-01 Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Jun 1, 2019
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control (idarubicin+cytarabine) Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Drug: Idarubicin; 12 mg/m2/day by slow (10 to 15 minutes) IV injection daily on days 1, 2 and 3 of induction therapy, and on days 1 and 2 of re-induction therapy; Other Names: Idamycin ; Drug: Cytarabine; 100 mg/m2/day by continuous IV infusion on days 1 through 7 of induction therapy, and on days 1 through 5 of re-induction therapy 1.0 g/m2 IV infusion given over 3 hours every 12 hours on days 1, 3, and 5 of consolidation therapy
Experimental: Dociparstat 0.125 mg/kg Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Drug: CX-01; 4 mg/kg IV bolus followed by doses of 0.125, or 0.25 mg/kg/hr given on days 1 through 7 with standard induction therapy, on days 1 through 5 or 7 with standard re-induction therapy, and on days 1, 3 and 5 with standard consolidation therapy; Other Names: 2-O, 3-O desulfated heparin ODSH PGX-100 ; Drug: Idarubicin; 12 mg/m2/day by slow (10 to 15 minutes) IV injection daily on days 1, 2 and 3 of induction therapy, and on days 1 and 2 of re-induction therapy; Other Names: Idamycin ; Drug: Cytarabine; 100 mg/m2/day by continuous IV infusion on days 1 through 7 of induction therapy, and on days 1 through 5 of re-induction therapy 1.0 g/m2 IV infusion given over 3 hours every 12 hours on days 1, 3, and 5 of consolidation therapy
Experimental: Dociparstat 0.25 mg/kg Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Drug: CX-01; 4 mg/kg IV bolus followed by doses of 0.125, or 0.25 mg/kg/hr given on days 1 through 7 with standard induction therapy, on days 1 through 5 or 7 with standard re-induction therapy, and on days 1, 3 and 5 with standard consolidation therapy; Other Names: 2-O, 3-O desulfated heparin ODSH PGX-100 ; Drug: Idarubicin; 12 mg/m2/day by slow (10 to 15 minutes) IV injection daily on days 1, 2 and 3 of induction therapy, and on days 1 and 2 of re-induction therapy; Other Names: Idamycin ; Drug: Cytarabine; 100 mg/m2/day by continuous IV infusion on days 1 through 7 of induction therapy, and on days 1 through 5 of re-induction therapy 1.0 g/m2 IV infusion given over 3 hours every 12 hours on days 1, 3, and 5 of consolidation therapy

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Who Achieved Morphologic Complete Remission [during induction and re-induction phases of treatment (up to 60 days after the start of each treatment cycle)]

   Morphologic complete remission (CR) was evaluated by IWG criteria and defined as ANC >1000/microliter; platelet count >100,000, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease.

Secondary Outcome Measures

1. Duration of Event-free Survival [randomization through treatment failure]

   Event-free survival was measured as time from randomization until treatment failure. Treatment failure was defined as failure to achieve composite completed morphological remission during the induction and re-induction phase of the study lasting up to 60 days, relapse from complete response, or death from any cause, whichever occurred first. Assessments were performed every 3 months and continued until death or 18 months after the last subject was randomized, whichever occurred first.

2. Time to Leukemia-free Survival [Randomization until disease relapse or death from any cause, whichever occurred first.]

   Leukemia-free survival was assessed as a secondary endpoint only in subjects who achieved composite complete remission and was measured from randomization until disease relapse or death from any cause, whichever occurred first. Assessments were performed every 3 months until death or 18 months after the last subject was randomized, whichever occurred first.

3. Number of Subjects Who Achieved Overall Survival [Randomization until death or 18 months after the last patient was randomized, whichever occurred first.]

   Overall survival was measured from the date of randomization until death from any cause. Assessments were performed every 3 months and continued until death or 18 months after the last patient was randomized, whichever came first.

4. Number of Subjects Who Achieved Composite Complete Remission [Up to 60 days after the start of each treatment cycle]

   The composite complete remission (CR) rate included CR, CR without recovery of platelets (CRp), and CR without recovery of neutrophils and/or platelets (CRi), as defined by the International Working Group criteria during the induction and re-induction phases of treatment. CR was defined as an Absolute Neutrophil Count (ANC) >1000/μL, platelet count >100,000/μL, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease. CRi was defined as an ANC <1000/μL and/or platelet count <100,000/, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease.

5. Duration of Morphologic Complete Remission [Randomization until death or 18 months after the last patient was randomized, whichever occurred first.]

   The duration of morphologic complete remission was assessed only in subjects who had achieved morphologic complete remission and was defined as the time from achievement of complete response to the detection or relapse. Relapse was defined as the reappearance of leukemia blasts in the peripheral blood, >5% blasts in the bone marrow not attributable to another cause, or appearance/reappearance of extramedullary disease and with a bone marrow blast percentage of >5% but ≤20%. If the latter, a repeat bone marrow examination was performed at least 7 days after the first marrow examination; documentation of the bone marrow blast percentage of >5% was necessary to establish relapse. Assessments were performed every 3 months and continued until death or 18 months after the last subject was randomized, whichever occurred first. Duration of morphologic complete remission (time from the achievement of complete response to the detection of relapse)

6. Time to Recovery of Neutrophils [Randomization to ANC recovery, for up to 60 days after the start of each treatment cycle]

   Neutrophil recovery was assessed from randomization to Absolute Neutrophil Count (ANC) recovery (ANC >500/µL and >1000/µL) for up to 60 days after the start of each treatment cycle.

7. Time to Platelet Recovery [Randomization to platelet recovery, for up to 60 days after the start of each treatment cycle]

   Platelet recovery was measured from randomization to platelet recovery (platelet count >20,000/µL and >100,000/µL)

8. Number of Subjects Who Died by Day 30 [30 days (from first day of induction treatment to 30 days after)]

   Mortality (rate of death) of subjects by Day 30, measured from the first day of induction treatment to 30 days post-induction.

9. Number of Subjects Who Died by Day 60. [60 days (from the first day of induction treatment to 60 days after)]

   Mortality (rate of death) of subjects by Day 60, measured from the first day of induction treatment to 60 days post-induction.

10. Number of Subjects Who Died by Day 90 [90 days (from the first day of induction treatment to 90 days after)]

    Mortality (rate of death) of subjects at Day 90, measured from the first day of induction treatment to 90 days post-induction.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Newly diagnosed, de novo or secondary, previously untreated AML

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

Exclusion Criteria:

• Acute promyelocytic leukemia

• Prior chemotherapy for AML

• Prior intensive chemotherapy or stem cell transplantation for the treatment of myelodysplastic syndrome

• CNS leukemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego, Moores Cancer Center	La Jolla	California	United States	92093
2	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
3	George Washington University	Washington	District of Columbia	United States	20037
4	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
5	June E. Nylen Cancer Center	Sioux City	Iowa	United States	51101
6	Norton Cancer Institute	Louisville	Kentucky	United States	40207
7	Tulane University/Tulane Cancer Center	New Orleans	Louisiana	United States	70112
8	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
9	Allina Health - Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
10	Washington University School of Medicine in St. Louis	Saint Louis	Missouri	United States	63110
11	New Mexico Cancer Care Alliance	Albuquerque	New Mexico	United States	87131
12	Montefiore Medical Center	Bronx	New York	United States	10467
13	Northwell Health, Monter Cancer Center	Lake Success	New York	United States	11042
14	University of Cincinnati	Cincinnati	Ohio	United States	45267
15	Oregon Health & Science University Knight Cancer Institute	Portland	Oregon	United States	97239
16	Rhode Island Hospital	Providence	Rhode Island	United States	02903
17	Medical University of South Carolina	Charleston	South Carolina	United States	29425
18	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
19	Tennessee Oncology/Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
20	Baylor Research Institute/Baylor Sammons Cancer Center/Baylor University Medical Center	Dallas	Texas	United States	75246
21	Methodist Healthcare System of San Antonio	San Antonio	Texas	United States	78229
22	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
23	LDS Hospital	Salt Lake City	Utah	United States	84143

Sponsors and Collaborators

• Chimerix

Investigators

• Study Director: Stephen Marcus, MD, Cantex Pharmaceuticals. Inc.

Study Documents (Full-Text)

• Study Protocol - Jan 13, 2017
• Statistical Analysis Plan - Mar 20, 2018

More Information

Publications

None provided.

• Responsible Party: Chimerix
• ClinicalTrials.gov Identifier: NCT02873338
• Other Study ID Numbers: CNTX-CX-01-2015-AML-1
• First Posted: Aug 19, 2016
• Last Update Posted: Oct 29, 2021
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cytarabine; Idarubicin; Heparin

Study Results

Participant Flow

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Period Title: Overall Study
STARTED	26	25	24
COMPLETED	8	4	6
NOT COMPLETED	18	21	18

Baseline Characteristics

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg	Total
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Total of all reporting groups
Overall Participants	26	25	24	75
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67 (3.6)	67 (4.8)	68 (4.3)	67 (4.2)
Sex: Female, Male (Count of Participants)
Female	6 23.1%	10 40%	13 54.2%	29 38.7%
Male	20 76.9%	15 60%	11 45.8%	46 61.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 4%	1 4.2%	2 2.7%
Asian	1 3.8%	0 0%	0 0%	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 7.7%	1 4%	1 4.2%	4 5.3%
White	23 88.5%	22 88%	20 83.3%	65 86.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 4%	2 8.3%	3 4%
AML (Count of Participants)
De novo	22 84.6%	18 72%	22 91.7%	62 82.7%
Secondary	4 15.4%	7 28%	2 8.3%	13 17.3%
Time since AML diagnosis (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	1.1 (1.19)	1.2 (1.15)	1.0 (0.75)	1.1 (1.04)
Baseline blasts in bone marrow (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	44 (25.9)	47 (22.3)	46 (26.6)	46 (24.6)

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Who Achieved Morphologic Complete Remission
Description	Morphologic complete remission (CR) was evaluated by IWG criteria and defined as ANC >1000/microliter; platelet count >100,000, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease.
Time Frame	during induction and re-induction phases of treatment (up to 60 days after the start of each treatment cycle)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Count of Participants [Participants]	14 53.8%	8 32%	11 45.8%

2. Secondary Outcome

Title	Duration of Event-free Survival
Description	Event-free survival was measured as time from randomization until treatment failure. Treatment failure was defined as failure to achieve composite completed morphological remission during the induction and re-induction phase of the study lasting up to 60 days, relapse from complete response, or death from any cause, whichever occurred first. Assessments were performed every 3 months and continued until death or 18 months after the last subject was randomized, whichever occurred first.
Time Frame	randomization through treatment failure

Outcome Measure Data

Analysis Population Description

Note, in the Dociparstat 0.125 mg/kg group, fewer than half of the subjects achieved complete CR, and thus were assessed as having an event on Day 1.

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Median (Full Range) [days]	243.5	1	171.5

3. Secondary Outcome

Title	Time to Leukemia-free Survival
Description	Leukemia-free survival was assessed as a secondary endpoint only in subjects who achieved composite complete remission and was measured from randomization until disease relapse or death from any cause, whichever occurred first. Assessments were performed every 3 months until death or 18 months after the last subject was randomized, whichever occurred first.
Time Frame	Randomization until disease relapse or death from any cause, whichever occurred first.

Outcome Measure Data

Analysis Population Description

This analysis only included subjects who achieved composite complete remission. The following number of subjects were censored in each treatment group: Control: 6/16 (37.5%) subjects Dociparstat 0.125 mg/kg: 4/9 (44.4%) subjects Dociparstat 0.25 mg/kg: 10/15 (66.7%) subjects

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	16	9	15
Median (Full Range) [days]	292	448	166

4. Secondary Outcome

Title	Number of Subjects Who Achieved Overall Survival
Description	Overall survival was measured from the date of randomization until death from any cause. Assessments were performed every 3 months and continued until death or 18 months after the last patient was randomized, whichever came first.
Time Frame	Randomization until death or 18 months after the last patient was randomized, whichever occurred first.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Subjects died	14 53.8%	14 56%	9 37.5%
Subjects still alive	12 46.2%	11 44%	15 62.5%

5. Secondary Outcome

Title	Number of Subjects Who Achieved Composite Complete Remission
Description	The composite complete remission (CR) rate included CR, CR without recovery of platelets (CRp), and CR without recovery of neutrophils and/or platelets (CRi), as defined by the International Working Group criteria during the induction and re-induction phases of treatment. CR was defined as an Absolute Neutrophil Count (ANC) >1000/μL, platelet count >100,000/μL, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease. CRi was defined as an ANC <1000/μL and/or platelet count <100,000/, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease.
Time Frame	Up to 60 days after the start of each treatment cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Count of Participants [Participants]	16 61.5%	9 36%	15 62.5%

6. Secondary Outcome

Title	Duration of Morphologic Complete Remission
Description	The duration of morphologic complete remission was assessed only in subjects who had achieved morphologic complete remission and was defined as the time from achievement of complete response to the detection or relapse. Relapse was defined as the reappearance of leukemia blasts in the peripheral blood, >5% blasts in the bone marrow not attributable to another cause, or appearance/reappearance of extramedullary disease and with a bone marrow blast percentage of >5% but ≤20%. If the latter, a repeat bone marrow examination was performed at least 7 days after the first marrow examination; documentation of the bone marrow blast percentage of >5% was necessary to establish relapse. Assessments were performed every 3 months and continued until death or 18 months after the last subject was randomized, whichever occurred first. Duration of morphologic complete remission (time from the achievement of complete response to the detection of relapse)
Time Frame	Randomization until death or 18 months after the last patient was randomized, whichever occurred first.

Outcome Measure Data

Analysis Population Description

This analysis only included subjects who had achieved morphologic complete remission. The following number of subjects were censored in each treatment group for this analysis; however the full ranges include censored subjects: Control: 7/14 (50%) subjects Dociparstat 0.125 mg/kg: 6/8 (75.0%) subjects Dociparstat 0.25 mg/kg: 9/11 (81.8%) subjects

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	14	8	11
Median (Full Range) [days]	233	494	294

7. Secondary Outcome

Title	Time to Recovery of Neutrophils
Description	Neutrophil recovery was assessed from randomization to Absolute Neutrophil Count (ANC) recovery (ANC >500/µL and >1000/µL) for up to 60 days after the start of each treatment cycle.
Time Frame	Randomization to ANC recovery, for up to 60 days after the start of each treatment cycle

Outcome Measure Data

Analysis Population Description

The following number of subjects were censored in each treatment group for both analyses (neutrophil recovery to >500/µL and >1000/µL): Control: 6/26 (23.1%) subjects for both analyses (>500/µL and >1000/µL) Dociparstat 0.125 mg/kg: 9/25 (36.0%) subjects for both analyses (>500/µL and >1000/µL) Dociparstat 0.25 mg/kg: 7/24 (29.2%) subjects for >500/µL and 11/24 (45.8%) subjects for >1000/µL

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Recovery to >500/µL	32	43	29
Recovery to >1000/µL	37	42	35

8. Secondary Outcome

Title	Time to Platelet Recovery
Description	Platelet recovery was measured from randomization to platelet recovery (platelet count >20,000/µL and >100,000/µL)
Time Frame	Randomization to platelet recovery, for up to 60 days after the start of each treatment cycle

Outcome Measure Data

Analysis Population Description

The following number of subjects were censored in each treatment group for each analysis (platelet recovery to >20,000µL and >100,000µL): Control: 5/26 (19.2%) subjects for >20,000µL and 7/26 (26.9%) subjects for >100,000µL Dociparstat 0.125 mg/kg: 5/25 (20%) subjects for >20,000µL and 12/25 (48.0%) subjects for >100,000µL Dociparstat 0.25 mg/kg: 8/24 (33.3%) subjects for >20,000µL and 11/24 (45.8%) subjects for >100,000µL

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Recovery to >20,000µL	35	36	29
Recovery to >100,000µL	38	50	32

9. Secondary Outcome

Title	Number of Subjects Who Died by Day 30
Description	Mortality (rate of death) of subjects by Day 30, measured from the first day of induction treatment to 30 days post-induction.
Time Frame	30 days (from first day of induction treatment to 30 days after)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Count of Participants [Participants]	2 7.7%	1 4%	3 12.5%

10. Secondary Outcome

Title	Number of Subjects Who Died by Day 60.
Description	Mortality (rate of death) of subjects by Day 60, measured from the first day of induction treatment to 60 days post-induction.
Time Frame	60 days (from the first day of induction treatment to 60 days after)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Count of Participants [Participants]	2 7.7%	2 8%	3 12.5%

11. Secondary Outcome

Title	Number of Subjects Who Died by Day 90
Description	Mortality (rate of death) of subjects at Day 90, measured from the first day of induction treatment to 90 days post-induction.
Time Frame	90 days (from the first day of induction treatment to 90 days after)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control (Idarubicin+Cytarabine)	Dociparstat 0.125 mg/kg	Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)	Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
Measure Participants	26	25	24
Count of Participants [Participants]	2 7.7%	3 12%	3 12.5%

Adverse Events

Time Frame	From the date and time of first dose of study treatment to 30 days after the last dose of treatment, or if the event start date was prior to the date of first dose of study treatment and the severity worsened on or after the date and time of the first dose of study treatment.
Arm/Group Title	Control (Idarubicin+Cytarabine)		Dociparstat 0.125 mg/kg		Dociparstat 0.25 mg/kg
Arm/Group Description	Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)		Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)		Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7) Reinduction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2) Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)
All Cause Mortality
	Control (Idarubicin+Cytarabine)		Dociparstat 0.125 mg/kg		Dociparstat 0.25 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/25 (56%)		14/25 (56%)		9/23 (39.1%)
Serious Adverse Events
	Control (Idarubicin+Cytarabine)		Dociparstat 0.125 mg/kg		Dociparstat 0.25 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/25 (28%)		8/25 (32%)		13/23 (56.5%)
Blood and lymphatic system disorders
Febrile neutropenia	1/25 (4%)		3/25 (12%)		3/23 (13%)
Disseminated intravascular coagulation	1/25 (4%)		1/25 (4%)		1/23 (4.3%)
Haemorrhagic anaemia	0/25 (0%)		1/25 (4%)		0/23 (0%)
Cardiac disorders
Arrhythmia	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Cardio-respiratory arrest	1/25 (4%)		0/25 (0%)		0/23 (0%)
Pulseless electrical activity	0/25 (0%)		1/25 (4%)		0/23 (0%)
Gastrointestinal disorders
Colitis	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Gastric ulcer	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Ileus	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Lower gastrointestinal haemorrhage	1/25 (4%)		0/25 (0%)		0/23 (0%)
Small intestinal obstruction	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Vomiting	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
General disorders
Pyrexia	1/25 (4%)		0/25 (0%)		0/23 (0%)
Hepatobiliary disorders
Venoocclusive liver disease	0/25 (0%)		1/25 (4%)		0/23 (0%)
Infections and infestations
Pneumonia	1/25 (4%)		0/25 (0%)		1/23 (4.3%)
Bacteraemia	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Escherichia sepsis	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Pneumonia fungal	1/25 (4%)		0/25 (0%)		0/23 (0%)
Sepsis	0/25 (0%)		1/25 (4%)		0/23 (0%)
Septic shock	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Urosepsis	1/25 (4%)		0/25 (0%)		0/23 (0%)
Injury, poisoning and procedural complications
Subdural haematoma	0/25 (0%)		1/25 (4%)		0/23 (0%)
Metabolism and nutrition disorders
Tumor lysis syndrome	0/25 (0%)		1/25 (4%)		0/23 (0%)
Nervous system disorders
Encephalopathy	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Haemorrhage intracranial	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/25 (4%)		1/25 (4%)		0/23 (0%)
Acute respiratory failure	0/25 (0%)		1/25 (4%)		0/23 (0%)
Hypoxia	0/25 (0%)		1/25 (4%)		0/23 (0%)
Pulmonary embolism	0/25 (0%)		0/25 (0%)		1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	Control (Idarubicin+Cytarabine)		Dociparstat 0.125 mg/kg		Dociparstat 0.25 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/25 (100%)		25/25 (100%)		23/23 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	14/25 (56%)		16/25 (64%)		17/23 (73.9%)
Anaemia	13/25 (52%)		12/25 (48%)		8/23 (34.8%)
Neutropenia	6/25 (24%)		5/25 (20%)		4/23 (17.4%)
Thrombocytopenia	7/25 (28%)		4/25 (16%)		3/23 (13%)
Leukopenia	3/25 (12%)		1/25 (4%)		1/23 (4.3%)
Disseminated intravascular coagulation	1/25 (4%)		2/25 (8%)		1/23 (4.3%)
Cardiac disorders
Atrial fibrillation	4/25 (16%)		3/25 (12%)		1/23 (4.3%)
Tachycardia	1/25 (4%)		3/25 (12%)		0/23 (0%)
Atrial flutter	2/25 (8%)		0/25 (0%)		0/23 (0%)
Sinus bradycardia	0/25 (0%)		2/25 (8%)		0/23 (0%)
Ventricular tachycardia	0/25 (0%)		2/25 (8%)		0/23 (0%)
Ear and labyrinth disorders
Ear pain	0/25 (0%)		2/25 (8%)		0/23 (0%)
Eye disorders
Vision blurred	1/25 (4%)		2/25 (8%)		1/23 (4.3%)
Eye irritation	2/25 (8%)		1/25 (4%)		0/23 (0%)
Eye pain	2/25 (8%)		1/25 (4%)		0/23 (0%)
Gastrointestinal disorders
Nausea	16/25 (64%)		15/25 (60%)		15/23 (65.2%)
Diarrhoea	14/25 (56%)		14/25 (56%)		15/23 (65.2%)
Constipation	10/25 (40%)		7/25 (28%)		9/23 (39.1%)
Abdominal pain	8/25 (32%)		5/25 (20%)		9/23 (39.1%)
Vomiting	6/25 (24%)		4/25 (16%)		8/23 (34.8%)
Stomatitis	4/25 (16%)		6/25 (24%)		5/23 (21.7%)
Dyspepsia	4/25 (16%)		2/25 (8%)		7/23 (30.4%)
Flatulence	2/25 (8%)		6/25 (24%)		2/23 (8.7%)
Abdominal distension	2/25 (8%)		4/25 (16%)		2/23 (8.7%)
Gastrooesophageal reflux disease	2/25 (8%)		5/25 (20%)		1/23 (4.3%)
Haemorrhoids	0/25 (0%)		6/25 (24%)		1/23 (4.3%)
Dry mouth	0/25 (0%)		3/25 (12%)		2/23 (8.7%)
Abdominal pain upper	0/25 (0%)		1/25 (4%)		2/23 (8.7%)
Chapped lips	2/25 (8%)		0/25 (0%)		0/23 (0%)
Haematochezia	1/25 (4%)		2/25 (8%)		0/23 (0%)
Ileus	1/25 (4%)		0/25 (0%)		2/23 (8.7%)
Lower gastrointestinal haemorrhage	2/25 (8%)		1/25 (4%)		0/23 (0%)
Mouth haemorrhage	3/25 (12%)		0/25 (0%)		0/23 (0%)
Oral pain	1/25 (4%)		2/25 (8%)		0/23 (0%)
Proctalgia	0/25 (0%)		2/25 (8%)		1/23 (4.3%)
Gingival pain	2/25 (8%)		0/25 (0%)		0/23 (0%)
General disorders
Oedema peripheral	14/25 (56%)		16/25 (64%)		12/23 (52.2%)
Pyrexia	13/25 (52%)		8/25 (32%)		9/23 (39.1%)
Fatigue	6/25 (24%)		11/25 (44%)		10/23 (43.5%)
Chills	6/25 (24%)		5/25 (20%)		4/23 (17.4%)
Mucosal inflammation	1/25 (4%)		4/25 (16%)		4/23 (17.4%)
Peripheral swelling	1/25 (4%)		2/25 (8%)		2/23 (8.7%)
Localised oedema	2/25 (8%)		1/25 (4%)		0/23 (0%)
Oedema	1/25 (4%)		0/25 (0%)		2/23 (8.7%)
Injection site bruising	2/25 (8%)		0/25 (0%)		0/23 (0%)
Non-cardiac chest pain	0/25 (0%)		2/25 (8%)		0/23 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	2/25 (8%)		0/25 (0%)		0/23 (0%)
Infections and infestations
Pneumonia	6/25 (24%)		2/25 (8%)		3/23 (13%)
Sepsis	2/25 (8%)		3/25 (12%)		1/23 (4.3%)
Clostridium difficile colitis	2/25 (8%)		3/25 (12%)		0/23 (0%)
Bacteraemia	1/25 (4%)		1/25 (4%)		2/23 (8.7%)
Candida infection	0/25 (0%)		1/25 (4%)		2/23 (8.7%)
Enterococcal infection	1/25 (4%)		2/25 (8%)		0/23 (0%)
Pneumonia fungal	2/25 (8%)		0/25 (0%)		0/23 (0%)
Sinusitis	0/25 (0%)		2/25 (8%)		0/23 (0%)
Injury, poisoning and procedural complications
Fall	4/25 (16%)		2/25 (8%)		3/23 (13%)
Contusion	1/25 (4%)		3/25 (12%)		1/23 (4.3%)
Procedural pain	1/25 (4%)		3/25 (12%)		1/23 (4.3%)
Infusion related reaction	1/25 (4%)		1/25 (4%)		2/23 (8.7%)
Transfusion reaction	0/25 (0%)		1/25 (4%)		2/23 (8.7%)
Skin abrasion	2/25 (8%)		0/25 (0%)		0/23 (0%)
Investigations
Platelet count decreased	8/25 (32%)		9/25 (36%)		7/23 (30.4%)
White blood cell count decreased	6/25 (24%)		7/25 (28%)		7/23 (30.4%)
Aspartate aminotransferase increased	5/25 (20%)		5/25 (20%)		5/23 (21.7%)
Neutrophil count decreased	4/25 (16%)		4/25 (16%)		7/23 (30.4%)
Alanine aminotransferase increased	4/25 (16%)		6/25 (24%)		4/23 (17.4%)
Lymphocyte count decreased	2/25 (8%)		4/25 (16%)		6/23 (26.1%)
Blood bilirubin increased	1/25 (4%)		4/25 (16%)		1/23 (4.3%)
Activated partial thromboplastin time prolonged	0/25 (0%)		2/25 (8%)		3/23 (13%)
Blood creatinine increased	2/25 (8%)		1/25 (4%)		1/23 (4.3%)
Weight decreased	1/25 (4%)		1/25 (4%)		2/23 (8.7%)
International normalised ration increased	0/25 (0%)		0/25 (0%)		3/23 (13%)
Metabolism and nutrition disorders
Hypokalaemia	15/25 (60%)		16/25 (64%)		13/23 (56.5%)
Decreased appetite	7/25 (28%)		10/25 (40%)		9/23 (39.1%)
Hypophosphataemia	9/25 (36%)		8/25 (32%)		9/23 (39.1%)
Hypocalcaemia	5/25 (20%)		5/25 (20%)		7/23 (30.4%)
Hypoalbuminaemia	3/25 (12%)		6/25 (24%)		5/23 (21.7%)
Hypomagnesaemia	3/25 (12%)		4/25 (16%)		6/23 (26.1%)
Hyperglycaemia	1/25 (4%)		7/25 (28%)		3/23 (13%)
Hyponatraemia	1/25 (4%)		3/25 (12%)		3/23 (13%)
Fluid overload	1/25 (4%)		4/25 (16%)		1/23 (4.3%)
Alkalosis	1/25 (4%)		1/25 (4%)		2/23 (8.7%)
Hypoglycaemia	0/25 (0%)		0/25 (0%)		2/23 (8.7%)
Malnutrition	2/25 (8%)		0/25 (0%)		0/23 (0%)
Vitamin D deficiency	2/25 (8%)		0/25 (0%)		0/23 (0%)
Hypernatraemia	1/25 (4%)		3/25 (12%)		3/23 (13%)
Musculoskeletal and connective tissue disorders
Muscular weakness	2/25 (8%)		4/25 (16%)		3/23 (13%)
Arthralgia	3/25 (12%)		3/25 (12%)		0/23 (0%)
Myalgia	1/25 (4%)		2/25 (8%)		1/23 (4.3%)
Pain in jaw	0/25 (0%)		2/25 (8%)		2/23 (8.7%)
Arthritis	0/25 (0%)		2/25 (8%)		0/23 (0%)
Nervous system disorders
Headache	6/25 (24%)		9/25 (36%)		6/23 (26.1%)
Dizziness	5/25 (20%)		5/25 (20%)		4/23 (17.4%)
Dysgeusia	1/25 (4%)		2/25 (8%)		1/23 (4.3%)
Encephalopathy	1/25 (4%)		0/25 (0%)		2/23 (8.7%)
Syncope	2/25 (8%)		0/25 (0%)		0/23 (0%)
Psychiatric disorders
Insomnia	8/25 (32%)		6/25 (24%)		6/23 (26.1%)
Anxiety	4/25 (16%)		2/25 (8%)		3/23 (13%)
Confusional state	0/25 (0%)		3/25 (12%)		3/23 (13%)
Depression	1/25 (4%)		0/25 (0%)		5/23 (21.7%)
Hallucination	1/25 (4%)		4/25 (16%)		1/23 (4.3%)
Delirium	3/25 (12%)		1/25 (4%)		1/23 (4.3%)
Agitation	1/25 (4%)		2/25 (8%)		0/23 (0%)
Renal and urinary disorders
Pollakiuria	4/25 (16%)		1/25 (4%)		4/23 (17.4%)
Acute kidney injury	1/25 (4%)		3/25 (12%)		2/23 (8.7%)
Haematuria	2/25 (8%)		2/25 (8%)		2/23 (8.7%)
Dysuria	0/25 (0%)		3/25 (12%)		2/23 (8.7%)
Urinary retention	0/25 (0%)		2/25 (8%)		1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/25 (36%)		6/25 (24%)		8/23 (34.8%)
Cough	8/25 (32%)		6/25 (24%)		5/23 (21.7%)
Epistaxis	9/25 (36%)		5/25 (20%)		2/23 (8.7%)
Oropharyngeal pain	4/25 (16%)		4/25 (16%)		2/23 (8.7%)
Hiccups	4/25 (16%)		1/25 (4%)		2/23 (8.7%)
Hypoxia	1/25 (4%)		4/25 (16%)		2/23 (8.7%)
Pulmonary oedema	1/25 (4%)		2/25 (8%)		4/23 (17.4%)
Wheezing	3/25 (12%)		3/25 (12%)		1/23 (4.3%)
Haemoptysis	2/25 (8%)		2/25 (8%)		2/23 (8.7%)
Pleural effusion	1/25 (4%)		1/25 (4%)		3/23 (13%)
Nasal congestion	1/25 (4%)		2/25 (8%)		1/23 (4.3%)
Productive cough	1/25 (4%)		1/25 (4%)		2/23 (8.7%)
Respiratory failure	2/25 (8%)		2/25 (8%)		0/23 (0%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	5/25 (20%)		7/25 (28%)		2/23 (8.7%)
Alopecia	5/25 (20%)		1/25 (4%)		1/23 (4.3%)
Dry skin	2/25 (8%)		2/25 (8%)		3/23 (13%)
Petechiae	2/25 (8%)		4/25 (16%)		1/23 (4.3%)
Pruritus	2/25 (8%)		1/25 (4%)		2/23 (8.7%)
Urticaria	2/25 (8%)		1/25 (4%)		2/23 (8.7%)
Drug eruption	3/25 (12%)		0/25 (0%)		1/23 (4.3%)
Rash	1/25 (4%)		2/25 (8%)		1/23 (4.3%)
Rash erythematous	1/25 (4%)		2/25 (8%)		1/23 (4.3%)
Erythema	0/25 (0%)		2/25 (8%)		0/23 (0%)
Rash follicular	0/25 (0%)		0/25 (0%)		2/23 (8.7%)
Vascular disorders
Hypertension	4/25 (16%)		6/25 (24%)		6/23 (26.1%)
Hypotension	4/25 (16%)		4/25 (16%)		3/23 (13%)
Deep vein thrombosis	2/25 (8%)		4/25 (16%)		0/23 (0%)
Thrombophlebitis superficial	1/25 (4%)		2/25 (8%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Details of the Study and its results shall not be publicized or published in any form without prior consent of the Sponsor.