Study of Voreloxin (Vosaroxin) in Older Patients With Untreated Acute Myeloid Leukemia

• Sponsor: Sunesis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00607997
• Collaborator: (none)
• Enrollment: 113
• Locations: 20
• Arm: 1
• Actual Duration (Months): 18.3
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate the overall remission rate of treatment with vosaroxin (formerly voreloxin) Injection in patients at least 60 years of age with previously untreated AML

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Acute Disease; Acute Myeloid Leukemia; Nonlymphocytic Leukemia; Myelodysplastic Syndromes	Drug: vosaroxin	Phase 2

Detailed Description

Other objectives of this study include:

1. Assess the safety of treatment with vosaroxin, including the 30 and 60 day all-cause mortality

2. Assess leukemia free survival (LFS), event-free survival (EFS), overall survival (OS), and duration of remission (DR).

3. Characterize the pharmacokinetic (PK) profile of vosaroxin in this patient population.

4. Evaluate potential stratification biomarkers by evaluating DNA-damage and apoptotic pathways in bone marrow samples before and after treatment with vosaroxin

Study Design

• Study Type: Interventional
• Actual Enrollment: 113 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Multicenter Clinical Study of the Safety and Efficacy of Voreloxin (Vosaroxin) Injection in Patients Equal to or Greater Than 60 Years of Age With Previously Untreated Acute Myeloid Leukemia
• Actual Study Start Date: May 15, 2008
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 23, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: All Study Patients Schedule A: 72 mg/m2 vosaroxin Days 1, 8 and 15 Schedule B: 72 mg/m2 vosaroxin on Days 1 and 8 Schedule C: 72 mg/m2 on Days 1 and 4, or Schedule C: 90 mg/m2 on Days 1 and 4

Drug: vosaroxin; Vosaroxin was administered by slow intravenous (IV) infusion or via syringe pump within 10 minutes.Patients could have completed up to 4 treatment cycles consisting of 1 or 2 induction treatment cycles and up to 2 consolidation treatment cycles. For Schedule A, an induction cycle was a minimum of 21 days during which patients received vosaroxin on Days 1, 8, and 15, followed by weekly observations until hematologic recovery for patients with aplastic marrow after the postinduction bone marrow assessment. For Schedules B and C, an induction cycle was a minimum of 15 days, during which patients received vosaroxin on Days 1 and 8 (Schedule B), or Days 1 and 4 (Schedule C), followed by the same weekly observations until hematologic recovery as for Schedule A.; Other Names: voreloxin SNS-595

Outcome Measures

Primary Outcome Measures

1. Remission Rate Defined as the Percentage of Patients Whose Respnse is CR or CRp Based on International Working Group (IWG) Response Criteria and Treatment Outcomes Definitions [2 years]

   Combined remission rate (complete remission [CR] + complete remission with incomplete platelet recovery [CRp]) of vosaroxin of patients ≥ 60 years old with previously untreated (de novo or secondary) AML are presented by treatment group for all treated analysis set. Per IWG criteria, a CR requires bone marrow blasts < 5%, absolute neutrophil count (ANC) > 1000 cells/uL, and platelet (plt) count > 100,000 plt/uL. The criteria for CRp are the same as those for CR, except for platelet count <= 100,000 lt/uL. Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (Morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.

Secondary Outcome Measures

1. Leukemia-free Survival (LFS) [2 years]

   The censor date was the last known alive date without report of relapse.

2. Overall Survival [2 years]

3. Pharmacokinetics Day 1 - Cmax (ng/mL) [1 Day]

   Pharmacokinetic Parameters (Cmax) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

4. Pharmacokinetics Day 4 Cmax (ng/mL) [Day 4]

   Pharmacokinetic Parameters by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) on Day 4 Please note that N, mean and CV% are reported, but CV% is not an option in the drop down menu. So Standard Deviation is really CV% in the table.

5. All Cause Mortality [30 and 60 days]

   Mortality of those patients enrolled in the study and receiving intervention

6. Pharmacokinetics Day 1 - AUC0-72 and AUCinf (hr*ng/mL) [1 Day]

   Pharmacokinetic Parameters (AUC0-72 and AUCinf ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

7. Pharmacokinetics Day 1 - t1/2 (hr) and MRTinf (hr) [1 Day]

   Pharmacokinetic Parameters (t1/2 and and MRTinf) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

8. Pharmacokinetics Day 1 - CL (L/hr) [1 Day]

   Pharmacokinetic Parameters (CL) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

9. Pharmacokinetics Day 1 - Vss (L) [1 Day]

   Pharmacokinetic Parameters (Vss ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

10. Pharmacokinetics Day 4 - AUC0-72 and AUCinf (hr*ng/mL) [Day 4]

    Pharmacokinetic Parameters (AUC0-72 and AUCinf ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. Standard Deviation is really CV% in the table.

11. Pharmacokinetics Day 4 - t1/2 (hr) and MRTinf (hr) [Day 4]

    Pharmacokinetic Parameters (t1/2 and and MRTinf) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The Standard Deviation is really CV% in the table.

12. Pharmacokinetics Day 4 - CL (L/hr) [Day 4]

    Pharmacokinetic Parameters (CL) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

13. Pharmacokinetics Day 4 - Vss (L) [Day 4]

    Pharmacokinetic Parameters (Vss ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

1. At least 60 years of age and diagnosis of previously untreated AML (either de novo or from an antecedent hematologic disorder or therapy related AML)

2. At least 20% blasts by BM biopsy or aspirate

3. ECOG performance status of 0,1,or 2

4. Adequate cardiac, renal and liver function

Key Exclusion Criteria:

1. Uncontrolled DIC

2. Active central nervous system involvement by AML

3. Requiring hemodialysis or peritoneal dialysis

4. Some prior history of heart attack or stroke (depending on how long ago the event occurred)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259
3	Scripps Cancer Center	La Jolla	California	United States	92037
4	Rocky Mountain Blood and Marrow Transplant Program	Denver	Colorado	United States	80218
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	The University of Chicago	Chicago	Illinois	United States	60637
7	Indiana University Cancer Center	Indianapolis	Indiana	United States	46206
8	St. Francis Hospital & Health Systems at Beech Grove Campus	Indianapolis	Indiana	United States	46237
9	Cancer Center of Kansas	Wichita	Kansas	United States	67208
10	Cancer Center of Kansas	Wichita	Kansas	United States	67214
11	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana	United States	71103
12	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
13	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
14	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
15	University of MO Ellis Fischel Cancer Center	Columbia	Missouri	United States	65203
16	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
17	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
18	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
19	MD Anderson Cancer Center	Houston	Texas	United States	77030
20	Huntsman Cancer Institute at the University of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• Sunesis Pharmaceuticals

Investigators

• Study Director: Adam Craig, MD, Sunesis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunesis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00607997
• Other Study ID Numbers: SPO-0014
• First Posted: Feb 6, 2008
• Last Update Posted: Jun 28, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Sunesis Pharmaceuticals: Leukemia; Myeloid; Elderly; Hematologic; Blood; Cancer; Malignancy; SNS-595; Sunesis; Hematologic Diseases; Myelodysplastic Syndromes; Older; voreloxin; reveal-1
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Acute Disease

Study Results

Participant Flow

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Period Title: Overall Study
STARTED	29	35	29	20
COMPLETED	2	8	5	4
NOT COMPLETED	27	27	24	16

Baseline Characteristics

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4	Total
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.	Total of all reporting groups
Overall Participants	29	35	29	20	113
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.1 (6.20)	74.2 (5.85)	70.5 (5.68)	76.5 (5.70)	73.6 (6.14)
Sex: Female, Male (Count of Participants)
Female	10 34.5%	12 34.3%	15 51.7%	3 15%	40 35.4%
Male	19 65.5%	23 65.7%	14 48.3%	17 85%	73 64.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.4%	0 0%	2 6.9%	0 0%	3 2.7%
Not Hispanic or Latino	28 96.6%	35 100%	27 93.1%	20 100%	110 97.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 6.9%	4 11.4%	1 3.4%	0 0%	7 6.2%
White	26 89.7%	31 88.6%	26 89.7%	19 95%	102 90.3%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.4%	0 0%	2 6.9%	1 5%	4 3.5%

Outcome Measures

1. Primary Outcome

Title	Remission Rate Defined as the Percentage of Patients Whose Respnse is CR or CRp Based on International Working Group (IWG) Response Criteria and Treatment Outcomes Definitions
Description	Combined remission rate (complete remission [CR] + complete remission with incomplete platelet recovery [CRp]) of vosaroxin of patients ≥ 60 years old with previously untreated (de novo or secondary) AML are presented by treatment group for all treated analysis set. Per IWG criteria, a CR requires bone marrow blasts < 5%, absolute neutrophil count (ANC) > 1000 cells/uL, and platelet (plt) count > 100,000 plt/uL. The criteria for CRp are the same as those for CR, except for platelet count <= 100,000 lt/uL. Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (Morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The all treated analysis set Included all enrolled patients who received any amount of vosaroxin.

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4	Total
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.	Schedule A, B and C combined
Measure Participants	29	35	29	20	113
Number (95% Confidence Interval) [percentage of patients]	41.4	25.7	34.5	25.0	31.9

2. Secondary Outcome

Title	Leukemia-free Survival (LFS)
Description	The censor date was the last known alive date without report of relapse.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All treated analysis set

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4	Total
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.	Schedule A, B and C combined
Measure Participants	29	35	29	20	113
Median (95% Confidence Interval) [Months]	9.8	10.9	5.5	4.9	6.1

3. Secondary Outcome

Title	Overall Survival
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All treated patients

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4	Total
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.	Schedule A, B, and C combined
Measure Participants	29	35	29	20	113
Median (95% Confidence Interval) [Months]	8.6	5.8	7.8	5.6	7.0

4. Secondary Outcome

Title	Pharmacokinetics Day 1 - Cmax (ng/mL)
Description	Pharmacokinetic Parameters (Cmax) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 1. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for 10 patients in Schedule A, for 9 patients in Schedule B, for 6 patients in Schedule C, and for 8 patients in Schedule C.

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	10	9	6	8
Mean (Standard Deviation) [ng/mL]	3028 (48.7)	2450 (47.8)	2865 (47.8)	3328 (69.0)

5. Secondary Outcome

Title	Pharmacokinetics Day 4 Cmax (ng/mL)
Description	Pharmacokinetic Parameters by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) on Day 4 Please note that N, mean and CV% are reported, but CV% is not an option in the drop down menu. So Standard Deviation is really CV% in the table.
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data on Day 4 for 5 patients in Schedule C, and for 8 patients in Schedule C .

Arm/Group Title	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	5	8
Mean (Standard Deviation) [ng/mL]	5792 (114.9)	4148 (98.4)

6. Secondary Outcome

Title	All Cause Mortality
Description	Mortality of those patients enrolled in the study and receiving intervention
Time Frame	30 and 60 days

Outcome Measure Data

Analysis Population Description

All treated analysis set

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4	Total
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.	Schedule A, B and C combined
Measure Participants	29	35	29	20	113
30-Day	5 17.2%	3 8.6%	2 6.9%	2 10%	12 10.6%
60-Day	11 37.9%	13 37.1%	5 17.2%	6 30%	35 31%

7. Secondary Outcome

Title	Pharmacokinetics Day 1 - AUC0-72 and AUCinf (hr*ng/mL)
Description	Pharmacokinetic Parameters (AUC0-72 and AUCinf ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 1. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for 10 patients in Schedule A, for 9 patients in Schedule B, for 6 patients in Schedule C, and for 8 patients in Schedule C.

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	10	9	6	8
AUC0-72 (hr.ng/mL)	36721 (21.1)	40092 (28.7)	37401 (13.9)	38086 (28.0)
AUCinf (hr.ng/mL)	41903 (27.3)	47228 (28.7)	44848 (13.0)	43838 (31.8)

8. Secondary Outcome

Title	Pharmacokinetics Day 1 - t1/2 (hr) and MRTinf (hr)
Description	Pharmacokinetic Parameters (t1/2 and and MRTinf) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 1. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for 10 patients in Schedule A, for 8 patients in Schedule B, for 6 patients in Schedule C, and for 8 patients in Schedule C.

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	10	8	6	8
t1/2 (hr)	22.51 (36.6)	27.29 (21.2)	28.27 (32.1)	23.57 (25.2)
MRTinf (hr)	30.56 (41.4)	37.57 (23.5)	37.16 (36.8)	32.10 (27.0)

9. Secondary Outcome

Title	Pharmacokinetics Day 1 - CL (L/hr)
Description	Pharmacokinetic Parameters (CL) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 1. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for 10 patients in Schedule A, for 8 patients in Schedule B, for 6 patients in Schedule C, and for 8 patients in Schedule C.

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	10	8	6	8
Mean (Standard Deviation) [L/hr]	3.643 (30.0)	3.389 (33.4)	3.235 (15.2)	4.538 (25.3)

10. Secondary Outcome

Title	Pharmacokinetics Day 1 - Vss (L)
Description	Pharmacokinetic Parameters (Vss ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 1. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for 10 patients in Schedule A, for 8 patients in Schedule B, for 6 patients in Schedule C, and for 8 patients in Schedule C.

Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15	Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.	Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	10	8	6	8
Mean (Standard Deviation) [L]	107.9 (40.4)	129.9 (50.2)	116.6 (28.5)	139.2 (21.1)

11. Secondary Outcome

Title	Pharmacokinetics Day 4 - AUC0-72 and AUCinf (hr*ng/mL)
Description	Pharmacokinetic Parameters (AUC0-72 and AUCinf ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. Standard Deviation is really CV% in the table.
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data on Day 4, for 5 patients in Schedule C, and for 8 patients in Schedule C.

Arm/Group Title	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	5	8
AUC0-72 (hr.ng/mL)	35125 (23.8)	43667 (32.3)
AUCinf (hr.ng/mL)	40539 (26.9)	46462 (37.2)

12. Secondary Outcome

Title	Pharmacokinetics Day 4 - t1/2 (hr) and MRTinf (hr)
Description	Pharmacokinetic Parameters (t1/2 and and MRTinf) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The Standard Deviation is really CV% in the table.
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data, for 5 patients in Schedule C, and for 7 patients in Schedule C.

Arm/Group Title	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	5	7
t1/2 (hr)	23.52 (27.6)	20.41 (28.7)
MRTinf (hr)	31.83 (35.7)	27.79 (24.1)

13. Secondary Outcome

Title	Pharmacokinetics Day 4 - CL (L/hr)
Description	Pharmacokinetic Parameters (CL) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data on Day 4, for 5 patients in Schedule C, and for 7 patients in Schedule C.

Arm/Group Title	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	5	7
Mean (Standard Deviation) [L/hr]	4.387 (30.3)	4.882 (28.4)

14. Secondary Outcome

Title	Pharmacokinetics Day 4 - Vss (L)
Description	Pharmacokinetic Parameters (Vss ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data for Day 4, for 5 patients in Schedule C, and for 7 patients in Schedule C.

Arm/Group Title	Schedule C: 72 mg/m2 on Days 1 and 4	Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose	Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
Measure Participants	5	7
Mean (Standard Deviation) [L]	137.3 (39.5)	132.7 (34.0)

Adverse Events

Time Frame	Study Start: 15 May 2008, Study Completion: 23 November 2009.Treatment-Emergent Adverse Events
Arm/Group Title	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15		Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8		Schedule C: 72 mg/m2 on Days 1 and 4		Schedule C: 90 mg/m2 on Days 1 and 4
Arm/Group Description	The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.		Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.		Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose		Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.
All Cause Mortality
	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15		Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8		Schedule C: 72 mg/m2 on Days 1 and 4		Schedule C: 90 mg/m2 on Days 1 and 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/29 (86.2%)		31/35 (88.6%)		28/29 (96.6%)		19/20 (95%)
Serious Adverse Events
	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15		Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8		Schedule C: 72 mg/m2 on Days 1 and 4		Schedule C: 90 mg/m2 on Days 1 and 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/29 (86.2%)		29/35 (82.9%)		21/29 (72.4%)		17/20 (85%)
Blood and lymphatic system disorders
Disseminated Intravascular Coagulation	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Febrile neutropenia	6/29 (20.7%)		6/35 (17.1%)		6/29 (20.7%)		6/20 (30%)
Neutropenia	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Pancytopenia	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Thrombocytopenia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Cardiac disorders
Acute myocardial infarction	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Angina pectoris	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Atrial fibrillation	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Cardiac failure congestive	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Cardio-Respiratory arrest	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Cardiomyopathy	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Myocardial ischaemia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Ventricular extrasystoles	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Gastrointestinal disorders
Abdominal pain	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Gastrointestinal haemorrhage	0/29 (0%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Intestinal functional disorder	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Nausea	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Neutropenic colitis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Oesophagitis	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Stomatitis	3/29 (10.3%)		3/35 (8.6%)		2/29 (6.9%)		3/20 (15%)
Vomiting	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
General disorders
Death	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Multi-Organ failure	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Non-Cardiac chest pain	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Pyrexia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hepatobiliary disorders
Bile duct obstruction	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hyperbilirubinaemia	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Infections and infestations
Bacteraemia	2/29 (6.9%)		3/35 (8.6%)		2/29 (6.9%)		2/20 (10%)
Cellulitis	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Cellulitis orbital	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Clostridium difficile colitis	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Enterococcal bacteraemia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Escherichia bacteraemia	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Neutropenic sepsis	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Perirectal abscess	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Pneumonia	5/29 (17.2%)		11/35 (31.4%)		7/29 (24.1%)		4/20 (20%)
Pneumonia fungal	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Pseudomonal bacteraemia	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Pseudomonal sepsis	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Sepsis	1/29 (3.4%)		3/35 (8.6%)		2/29 (6.9%)		2/20 (10%)
Septic shock	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Sinusitis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Sinusitis fungal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Staphylococcal bacteraemia	2/29 (6.9%)		1/35 (2.9%)		1/29 (3.4%)		1/20 (5%)
Staphylococcal infection	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Staphylococcal sepsis	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Streptococcal bacteraemia	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Streptococcal sepsis	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Injury, poisoning and procedural complications
Subdural haematoma	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
subdural haemorrhage	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Therapeutic agent toxicity	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Investigations
Ejection fraction decreased	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Metabolism and nutrition disorders
Dehydration	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Failure to thrive	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Fluid overload	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Myositis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia recurrent	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Tumour lysis syndrome	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Nervous system disorders
Convulsion	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Grand mal convulsion	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Neuropathy peripheral	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Psychiatric disorders
Confusional state	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Suicidal ideation	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Renal and urinary disorders
Renal failure	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Renal failure acute	2/29 (6.9%)		1/35 (2.9%)		1/29 (3.4%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Epistaxis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Pleural effusion	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Pulmonary haemorrhage	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Pulmonary oedema	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Respiratory failure	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Skin and subcutaneous tissue disorders
Rash	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Vascular disorders
Deep vein thrombosis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15		Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8		Schedule C: 72 mg/m2 on Days 1 and 4		Schedule C: 90 mg/m2 on Days 1 and 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/29 (100%)		35/35 (100%)		29/29 (100%)		20/20 (100%)
Blood and lymphatic system disorders
Anaemia	12/29 (41.4%)		19/35 (54.3%)		19/29 (65.5%)		12/20 (60%)
Coagulopathy	1/29 (3.4%)		4/35 (11.4%)		2/29 (6.9%)		2/20 (10%)
Febrile neutropenia	10/29 (34.5%)		19/35 (54.3%)		14/29 (48.3%)		5/20 (25%)
Hilar lymphadenopathy	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Leukocytosis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Leukopenia	2/29 (6.9%)		5/35 (14.3%)		0/29 (0%)		1/20 (5%)
Lymph node calcification	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Lymphadenopathy	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Lymphadenopathy mediastinal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Lymphopenia	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Microcytic anaemia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Neutropenia	12/29 (41.4%)		9/35 (25.7%)		8/29 (27.6%)		5/20 (25%)
Pancytopenia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Splenomegaly	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Thrombocytopenia	12/29 (41.4%)		24/35 (68.6%)		20/29 (69%)		12/20 (60%)
Cardiac disorders
Acute myocardial infraction	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Angina pectoris	1/29 (3.4%)		1/35 (2.9%)		4/29 (13.8%)		0/20 (0%)
Arteriosclerosis coronary artery	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Atrial fibrillation	4/29 (13.8%)		4/35 (11.4%)		6/29 (20.7%)		4/20 (20%)
Atrial flutter	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Atrioventricular block	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Bradycardia	1/29 (3.4%)		0/35 (0%)		2/29 (6.9%)		3/20 (15%)
Bundle branch block	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Bundle branch block left	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Cardiac disorder	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Cardiac failure congestive	2/29 (6.9%)		1/35 (2.9%)		2/29 (6.9%)		0/20 (0%)
Cardiomegaly	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Coronary artery disease	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Left ventricular failure	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Mitral valve Disease	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Mitral valve incompetence	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Myocardial infraction	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Palpitations	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Pericardial cyst	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Pericardial effusion	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Pericarditis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Sinus bradycardia	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Sinus Tachycardia	1/29 (3.4%)		5/35 (14.3%)		3/29 (10.3%)		0/20 (0%)
Supraventricular extrasystoles	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Supraventricular Tachycardia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Tachycardia	11/29 (37.9%)		14/35 (40%)		5/29 (17.2%)		5/20 (25%)
Tricuspid valve incompetence	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Ventricular arrhythmia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Ventricular extrasystoles	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		1/20 (5%)
Congenital, familial and genetic disorders
Spondylolisthesis	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Ear and labyrinth disorders
Cerumen impaction	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Deafness bilateral	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Ear congestion	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Ear pain	2/29 (6.9%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Eustachian tube patulous	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Tinnitus	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hypoacusis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		2/20 (10%)
Eye disorders
Conjunctival discolouration	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Conjunctival haemorrhage	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Conjunctivitis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Dry eye	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Erythema of eyelid	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Eye haemorrhage	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Eye Oedema	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Eye Pruritus	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Eyelid disorder	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Eyelid oedema	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Eyelid ptosis	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Lacrimation increased	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Madarosis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Ocular hyperaemia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Ocular icterus	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Retinal haemorrhage	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Vision blurred	3/29 (10.3%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Visual disturbance	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Vitreous detachment	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Vitreous floaters	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/29 (3.4%)		1/35 (2.9%)		2/29 (6.9%)		0/20 (0%)
Abdominal distension	2/29 (6.9%)		5/35 (14.3%)		5/29 (17.2%)		6/20 (30%)
Abdominal pain	9/29 (31%)		6/35 (17.1%)		6/29 (20.7%)		3/20 (15%)
Abdominal pain lower	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Abdominal pain upper	1/29 (3.4%)		5/35 (14.3%)		0/29 (0%)		1/20 (5%)
Abdominal tenderness	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		2/20 (10%)
Anorectal disorder	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Aptyalism	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Ascites	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Bowel sounds abnormal	1/29 (3.4%)		3/35 (8.6%)		0/29 (0%)		1/20 (5%)
Breath odour	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Caecitis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Chapped lips	1/29 (3.4%)		3/35 (8.6%)		0/29 (0%)		0/20 (0%)
Colonic Pseudo-obstruction	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Constipation	12/29 (41.4%)		13/35 (37.1%)		5/29 (17.2%)		4/20 (20%)
Dental discomfort	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Diarrhoea	24/29 (82.8%)		27/35 (77.1%)		20/29 (69%)		14/20 (70%)
Diverticulum	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Dry mouth	6/29 (20.7%)		5/35 (14.3%)		4/29 (13.8%)		3/20 (15%)
Dyspepsia	5/29 (17.2%)		3/35 (8.6%)		6/29 (20.7%)		1/20 (5%)
Dysphagia	5/29 (17.2%)		9/35 (25.7%)		6/29 (20.7%)		1/20 (5%)
Enlarged uvula	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Enterocolitis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Faecal incontinence	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Flatulence	0/29 (0%)		3/35 (8.6%)		0/29 (0%)		1/20 (5%)
Gastritis	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Gastrointestinal haemorrhage	3/29 (10.3%)		2/35 (5.7%)		0/29 (0%)		1/20 (5%)
Gastrooesophageal reflux disease	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Gingival bleeding	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Gingival disorder	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Gingival pain	0/29 (0%)		5/35 (14.3%)		0/29 (0%)		1/20 (5%)
Gingival swelling	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Gingivitis	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Glossitis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Glossodynia	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Haematochezia	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Haemorrhoidal haemorrhage	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Haemorrhoids	5/29 (17.2%)		7/35 (20%)		2/29 (6.9%)		0/20 (0%)
Hiatus Hernia	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Ileus	0/29 (0%)		0/35 (0%)		0/29 (0%)		2/20 (10%)
Ileus paralytic	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Inguinal Hernia	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Intestinal obstruction	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Leukoplakia oral	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Lip blister	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Lip disorder	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Lip dry	3/29 (10.3%)		1/35 (2.9%)		1/29 (3.4%)		1/20 (5%)
Lip haemorrhage	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Lip pain	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Lip ulceration	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Malabsorption	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Melaena	1/29 (3.4%)		3/35 (8.6%)		0/29 (0%)		1/20 (5%)
Mouth haemorrhage	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Mouth ulceration	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Nausea	22/29 (75.9%)		21/35 (60%)		25/29 (86.2%)		11/20 (55%)
Odynophagia	4/29 (13.8%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Oedema mouth	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Oesophageal disorder	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Oesophageal Spasm	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Oesophageal stenosis	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Oesophagitis	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Oral discomfort	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Oral mucosal blistering	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Oral mucosal discolouration	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Oral mucosal petechiae	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Oral pain	2/29 (6.9%)		5/35 (14.3%)		5/29 (17.2%)		6/20 (30%)
Oral soft tissue disorder	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Palatal disorder	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Perianal erythema	1/29 (3.4%)		0/35 (0%)		3/29 (10.3%)		0/20 (0%)
Periodontal disease	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Poor dental condition	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Proctalgia	1/29 (3.4%)		1/35 (2.9%)		3/29 (10.3%)		1/20 (5%)
Rectal fissure	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Rectal spasm	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Retching	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Salivary gland disorder	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Salivary hypersecretion	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Stomatitis	18/29 (62.1%)		19/35 (54.3%)		15/29 (51.7%)		11/20 (55%)
Tongue blistering	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Tongue discolouration	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Tongue haematoma	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Tongue haemorrhage	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Tongue oedema	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Toothache	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Vomiting	16/29 (55.2%)		10/35 (28.6%)		15/29 (51.7%)		6/20 (30%)
General disorders
Application site hypersensitivity	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Asthenia	9/29 (31%)		14/35 (40%)		6/29 (20.7%)		3/20 (15%)
Axillary pain	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Catheter related complication	2/29 (6.9%)		1/35 (2.9%)		3/29 (10.3%)		2/20 (10%)
Catheter site erythema	1/29 (3.4%)		3/35 (8.6%)		1/29 (3.4%)		2/20 (10%)
Catheter site excoriation	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Catheter site haematoma	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Catheter site haemorrhage	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Catheter site inflammation	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Catheter site oedema	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Catheter site pain	1/29 (3.4%)		3/35 (8.6%)		5/29 (17.2%)		1/20 (5%)
Catheter site related reaction	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Catheter Thrombosis	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Chest discomfort	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Chest pain	3/29 (10.3%)		3/35 (8.6%)		4/29 (13.8%)		1/20 (5%)
Chills	8/29 (27.6%)		12/35 (34.3%)		8/29 (27.6%)		6/20 (30%)
Discomfort	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Early Satiety	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Face Oedema	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Facial pain	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Fatigue	15/29 (51.7%)		20/35 (57.1%)		12/29 (41.4%)		7/20 (35%)
Feeling cold	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Gait disturbance	1/29 (3.4%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Generalized oedema	1/29 (3.4%)		4/35 (11.4%)		1/29 (3.4%)		1/20 (5%)
Induration	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Infusion site pain	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Injection site bruising	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Injection site reaction	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Malaise	6/29 (20.7%)		2/35 (5.7%)		2/29 (6.9%)		2/20 (10%)
Mucosal Inflammation	1/29 (3.4%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Mucous membrane disorder	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Multi-Organ failure	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Nodule	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Non-Cardiac chest pain	1/29 (3.4%)		1/35 (2.9%)		2/29 (6.9%)		1/20 (5%)
Oedema	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Oedema peripheral	17/29 (58.6%)		17/35 (48.6%)		15/29 (51.7%)		9/20 (45%)
Pain	5/29 (17.2%)		2/35 (5.7%)		7/29 (24.1%)		3/20 (15%)
Performance status decreased	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Peripheral coldness	0/29 (0%)		1/35 (2.9%)		2/29 (6.9%)		0/20 (0%)
Pyrexia	5/29 (17.2%)		9/35 (25.7%)		7/29 (24.1%)		7/20 (35%)
Suprapubic pain	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Swelling	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Tenderness	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Hepatobiliary disorders
Cholecystitis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Cholelithiasis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Hyperbilirubinaemia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Jaundice	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Immune system disorders
Drug hypersensitivity	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Infections and infestations
Abscess	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Acinetobacter bacteraemia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Anorectal infection bacterial	0/29 (0%)		1/35 (2.9%)		2/29 (6.9%)		0/20 (0%)
Bacteraemia	2/29 (6.9%)		3/35 (8.6%)		0/29 (0%)		1/20 (5%)
Bacterial infection	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Bacteroides bacteraemia	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Bronchiolitis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Bronchitis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Candidiasis	3/29 (10.3%)		4/35 (11.4%)		1/29 (3.4%)		0/20 (0%)
Catheter related infection	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Catheter site cellulitis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Catheter site infection	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Cellulitis	2/29 (6.9%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Central line infection	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Chronic Sinusitis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Clostridial infection	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		1/20 (5%)
Clostridium difficile colitis	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Diverticulitis	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Enterococcal bacteraemia	3/29 (10.3%)		3/35 (8.6%)		0/29 (0%)		1/20 (5%)
Enterococcal infection	2/29 (6.9%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Epiglottitis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Folliculitis	1/29 (3.4%)		0/35 (0%)		2/29 (6.9%)		1/20 (5%)
Fungaemia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Fungal infection	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Fungal rash	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Fusarium infection	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Gingival infection	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Herpes simplex	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Herpes zoster	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Infection	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Lobar pneumonia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Localized infection	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Lung infection	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Nasopharyngitis	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Oral Candidiasis	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		2/20 (10%)
Oral fungal infection	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Parotitis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Pharyngitis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Pneumonia	5/29 (17.2%)		3/35 (8.6%)		4/29 (13.8%)		3/20 (15%)
Pneumonia fungal	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Pseudomonal sepsis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Pseudomonas infection	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Rectal abscess	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Rhinitis	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Sinusitis	1/29 (3.4%)		1/35 (2.9%)		2/29 (6.9%)		0/20 (0%)
Skin infection	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Staphylococcal bacteraemia	3/29 (10.3%)		3/35 (8.6%)		1/29 (3.4%)		0/20 (0%)
Staphylococcal infection	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Stenotrophomonas infection	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Tooth abscess	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Upper respiratory tract infection	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Urinary tract infection	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		2/20 (10%)
Urinary tract infection enterococcal	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Urinary tract infection fungal	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Urinary tract infection pseudomonal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Urinary tract infection staphylococcal	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Vaginal candidiasis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Injury, poisoning and procedural complications
Allergic transfusion reaction	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Anaphylactic transfusion reaction	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Contusion	3/29 (10.3%)		2/35 (5.7%)		2/29 (6.9%)		0/20 (0%)
Excoriation	0/29 (0%)		0/35 (0%)		3/29 (10.3%)		2/20 (10%)
Fall	3/29 (10.3%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Head injury	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Incision site erythema	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Incision site haemorrhage	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Injury	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Joint Injury	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Post procedural complication	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Post procedural haematoma	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Post procedural haemorrhage	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Procedural pain	0/29 (0%)		5/35 (14.3%)		3/29 (10.3%)		1/20 (5%)
Skin injury	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Skin laceration	3/29 (10.3%)		2/35 (5.7%)		0/29 (0%)		1/20 (5%)
Spinal compression fracture	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Subdural haematoma	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Tooth fracture	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Tracheal deviation	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Transfusion reaction	3/29 (10.3%)		1/35 (2.9%)		3/29 (10.3%)		2/20 (10%)
Upper limb fracture	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Wound	2/29 (6.9%)		2/35 (5.7%)		2/29 (6.9%)		0/20 (0%)
Wound complication	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Investigations
Alanine aminotransferase increased	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Aspartate aminotransferase increased	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Bacteria sputum identified	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Bacteria urine identified	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Bacterial culture positive	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Blood alkaline phosphatase increased	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Blood creatinine increased	3/29 (10.3%)		3/35 (8.6%)		0/29 (0%)		1/20 (5%)
Blood culture positive	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Blood glucose increased	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Blood lactate dehydrogenase increased	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Blood testosterone decreased	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Blood urea increased	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Blood uric acid increased	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Body temperature decreased	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Breath sounds abnormal	7/29 (24.1%)		6/35 (17.1%)		3/29 (10.3%)		1/20 (5%)
C-Reactive protein increased	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Cardiac murmur	0/29 (0%)		4/35 (11.4%)		0/29 (0%)		0/20 (0%)
Chest x-ray abnormal	1/29 (3.4%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Clostridium difficile toxin test positive	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Culture urine positive	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Ejection fraction decreased	2/29 (6.9%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Electrocardiogram qrs complex abnormal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Electrocardiogram qt corrected interval prolonged	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Electrocardiogram qt prolonged	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Electrocardiogram st segment abnormal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Electrocardiogram st segment depression	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Electrocardiogram st-t change	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Electrocardiogram st-t segment abnormal	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Electrocardiogram t wave abnormal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Electrocardiogram t wave inversion	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Heart rate irregular	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Helicobacter pylori identification test positive	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Hepatic enzyme increased	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Hepatitis a antibody positive	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
International normalised ratio increased	4/29 (13.8%)		2/35 (5.7%)		2/29 (6.9%)		3/20 (15%)
Liver function test abnormal	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Liver scan abnormal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Lymph node palpable	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Nuclear magnetic resonance imaging brain abnormal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Oxygen consumption increased	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Oxygen saturation decreased	0/29 (0%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Prostate examination abnormal	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Prothrombin level increased	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Prothrombin time prolonged	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Pulse pressure decreased	0/29 (0%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Pulse pressure increased	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Radial pulse abnormal	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Respiratory rate increased	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Skin turgor decreased	1/29 (3.4%)		4/35 (11.4%)		0/29 (0%)		1/20 (5%)
Sputum culture positive	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Transaminases increased	1/29 (3.4%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Troponin i increased	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Urine analysis abnormal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Urine colour abnormal	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Urine output decreased	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Weight decreased	6/29 (20.7%)		3/35 (8.6%)		3/29 (10.3%)		3/20 (15%)
Weight increased	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
White blood cell count decreased	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
X-Ray abnormal	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Xanthochromia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Bacteria tissue specimen identified	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Metabolism and nutrition disorders
Acidosis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Anorexia	21/29 (72.4%)		18/35 (51.4%)		17/29 (58.6%)		11/20 (55%)
Cachexia	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Decreased appetite	0/29 (0%)		4/35 (11.4%)		2/29 (6.9%)		0/20 (0%)
Dehydration	7/29 (24.1%)		7/35 (20%)		3/29 (10.3%)		4/20 (20%)
Diabetes mellitus	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Diabetes mellitus insulin-dependent	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Fluid retention	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Fluid overload	2/29 (6.9%)		3/35 (8.6%)		4/29 (13.8%)		0/20 (0%)
Gout	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hyperglycaemia	3/29 (10.3%)		7/35 (20%)		6/29 (20.7%)		3/20 (15%)
Hyperkalaemia	1/29 (3.4%)		3/35 (8.6%)		1/29 (3.4%)		1/20 (5%)
Hyperlipidaemia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hypermagnesaemia	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Hypernatraemia	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hyperphosphataemia	2/29 (6.9%)		4/35 (11.4%)		2/29 (6.9%)		1/20 (5%)
Hyperuricaemia	1/29 (3.4%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Hypoalbuminaemia	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		1/20 (5%)
Hypocalcaemia	8/29 (27.6%)		5/35 (14.3%)		9/29 (31%)		4/20 (20%)
Hypoglycaemia	0/29 (0%)		2/35 (5.7%)		1/29 (3.4%)		1/20 (5%)
Hypokalaemia	21/29 (72.4%)		19/35 (54.3%)		17/29 (58.6%)		14/20 (70%)
Hypomagnesaemia	15/29 (51.7%)		14/35 (40%)		14/29 (48.3%)		7/20 (35%)
Hyponatraemia	2/29 (6.9%)		6/35 (17.1%)		2/29 (6.9%)		0/20 (0%)
Hypophosphataemia	13/29 (44.8%)		8/35 (22.9%)		6/29 (20.7%)		6/20 (30%)
Hypovolaemia	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Malnutrition	3/29 (10.3%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Metabolic acidosis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Oral intake reduced	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/29 (6.9%)		5/35 (14.3%)		4/29 (13.8%)		1/20 (5%)
Arthritis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Back pain	5/29 (17.2%)		7/35 (20%)		5/29 (17.2%)		1/20 (5%)
Bone pain	1/29 (3.4%)		1/35 (2.9%)		2/29 (6.9%)		1/20 (5%)
Chondrocalcinosis pyrophosphate	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Flank pain	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		1/20 (5%)
Groin pain	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Joint range of motion decreased	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Joint stiffness	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Limb discomfort	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Muscle spasms	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Muscular weakness	4/29 (13.8%)		4/35 (11.4%)		3/29 (10.3%)		1/20 (5%)
Musculoskeletal chest pain	2/29 (6.9%)		2/35 (5.7%)		3/29 (10.3%)		2/20 (10%)
Musculoskeletal discomfort	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Musculoskeletal pain	4/29 (13.8%)		5/35 (14.3%)		4/29 (13.8%)		3/20 (15%)
Musculoskeletal stiffness	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Myalgia	3/29 (10.3%)		4/35 (11.4%)		2/29 (6.9%)		0/20 (0%)
Neck pain	0/29 (0%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Osteitis	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Osteoarthritis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Osteopenia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Osteosclerosis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Pain in extremity	4/29 (13.8%)		5/35 (14.3%)		7/29 (24.1%)		2/20 (10%)
Pain in jaw	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Scoliosis	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Spinal osteoarthritis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Spondylolysis	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Temporomandibular joint syndrome	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Lung neoplasm	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Meningioma	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Tumour lysis syndrome	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Nervous system disorders
Ageusia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Aphasia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Carotid artery occlusion	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Cerebral ischaemia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Convulsion	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Coordination abnormal	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Dizziness	6/29 (20.7%)		7/35 (20%)		7/29 (24.1%)		4/20 (20%)
Dysarthria	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Dysgeusia	4/29 (13.8%)		5/35 (14.3%)		3/29 (10.3%)		5/20 (25%)
Encephalopathy	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Extrapyramidal disorder	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Headache	10/29 (34.5%)		9/35 (25.7%)		9/29 (31%)		2/20 (10%)
Hemiparesis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hypoaesthesia	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Hypogeusia	1/29 (3.4%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Hyporeflexia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hyposmia	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Intention tremor	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Lethargy	1/29 (3.4%)		2/35 (5.7%)		4/29 (13.8%)		3/20 (15%)
Memory impairment	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Nervous system disorder	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Neuralgia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Neuropathy	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Neuropathy peripheral	1/29 (3.4%)		1/35 (2.9%)		2/29 (6.9%)		1/20 (5%)
Paraesthesia	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Parosmia	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Peripheral sensory neuropathy	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Periventricular leukomalacia	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Restless legs syndrome	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Somnolence	4/29 (13.8%)		4/35 (11.4%)		2/29 (6.9%)		1/20 (5%)
Speech disorder	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Syncope	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Syncope vasovagal	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Transient ischaemic attack	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Tremor	1/29 (3.4%)		2/35 (5.7%)		2/29 (6.9%)		0/20 (0%)
Psychiatric disorders
Agitation	6/29 (20.7%)		0/35 (0%)		4/29 (13.8%)		3/20 (15%)
Anxiety	7/29 (24.1%)		14/35 (40%)		12/29 (41.4%)		4/20 (20%)
Apathy	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Confusional state	8/29 (27.6%)		9/35 (25.7%)		7/29 (24.1%)		3/20 (15%)
Delirium	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Delusion	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Depressed mood	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Depression	5/29 (17.2%)		5/35 (14.3%)		6/29 (20.7%)		2/20 (10%)
Disorientation	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Dysthymic disorder	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Flat affect	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hallucination	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		2/20 (10%)
Insomnia	12/29 (41.4%)		13/35 (37.1%)		11/29 (37.9%)		3/20 (15%)
Mental disorder	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Mental status changes	0/29 (0%)		3/35 (8.6%)		2/29 (6.9%)		1/20 (5%)
Mood altered	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Psychotic disorder	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Restlessness	3/29 (10.3%)		3/35 (8.6%)		0/29 (0%)		0/20 (0%)
Suicidal ideation	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Renal and urinary disorders
Bladder diverticulum	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Bladder pain	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Bladder spasm	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Dysuria	3/29 (10.3%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Haematuria	4/29 (13.8%)		11/35 (31.4%)		2/29 (6.9%)		0/20 (0%)
Haemorrhage urinary tract	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Incontinence	2/29 (6.9%)		3/35 (8.6%)		0/29 (0%)		0/20 (0%)
Nephrolithiasis	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Nocturia	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Oliguria	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Pollakiuria	2/29 (6.9%)		1/35 (2.9%)		2/29 (6.9%)		2/20 (10%)
Renal cyst	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Renal failure	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Renal failure acute	1/29 (3.4%)		3/35 (8.6%)		2/29 (6.9%)		0/20 (0%)
Renal mass	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Residual urine	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Stress urinary incontinence	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Urinary incontinence	3/29 (10.3%)		4/35 (11.4%)		1/29 (3.4%)		2/20 (10%)
Urinary retention	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Breast pain	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Pelvic fluid collection	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Penile oedema	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Penile pain	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Scrotal erythema	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Scrotal oedema	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Vulval disorder	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Vulvovaginal pruritus	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Acute respiratory failure	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Aspiration	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Asthma	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Atelectasis	2/29 (6.9%)		4/35 (11.4%)		5/29 (17.2%)		2/20 (10%)
Cough	13/29 (44.8%)		11/35 (31.4%)		11/29 (37.9%)		6/20 (30%)
Diaphragmalgia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Dysphonia	0/29 (0%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Dyspnoea	11/29 (37.9%)		14/35 (40%)		11/29 (37.9%)		6/20 (30%)
Dyspnoea exertional	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Epiglottic oedema	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Epistaxis	7/29 (24.1%)		13/35 (37.1%)		8/29 (27.6%)		5/20 (25%)
Haemoptysis	3/29 (10.3%)		8/35 (22.9%)		2/29 (6.9%)		0/20 (0%)
Hiccups	2/29 (6.9%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Hypoventilation	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hypoxia	3/29 (10.3%)		6/35 (17.1%)		6/29 (20.7%)		2/20 (10%)
Lung consolidation	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Lung disorder	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Lung infiltration	2/29 (6.9%)		1/35 (2.9%)		2/29 (6.9%)		1/20 (5%)
Nasal congestion	0/29 (0%)		3/35 (8.6%)		0/29 (0%)		0/20 (0%)
Nasal dryness	1/29 (3.4%)		2/35 (5.7%)		1/29 (3.4%)		0/20 (0%)
Obstructive airways disorder	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Orthopnoea	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Pharyngeal inflammation	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Pharyngeal oedema	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Pharyngolaryngeal pain	2/29 (6.9%)		4/35 (11.4%)		4/29 (13.8%)		3/20 (15%)
Pleural effusion	7/29 (24.1%)		6/35 (17.1%)		11/29 (37.9%)		2/20 (10%)
Pleuritic pain	2/29 (6.9%)		3/35 (8.6%)		0/29 (0%)		0/20 (0%)
Pneumonitis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Productive cough	3/29 (10.3%)		4/35 (11.4%)		3/29 (10.3%)		1/20 (5%)
Pulmonary alveolar haemorrhage	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Pulmonary congestion	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		1/20 (5%)
Pulmonary embolism	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Pulmonary granuloma	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Pulmonary oedema	3/29 (10.3%)		4/35 (11.4%)		4/29 (13.8%)		1/20 (5%)
Rales	10/29 (34.5%)		8/35 (22.9%)		2/29 (6.9%)		4/20 (20%)
Respiratory alkalosis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Respiratory distress	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Respiratory failure	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Rhinitis allergic	1/29 (3.4%)		6/35 (17.1%)		0/29 (0%)		0/20 (0%)
Rhinorrhoea	0/29 (0%)		0/35 (0%)		3/29 (10.3%)		0/20 (0%)
Rhonchi	3/29 (10.3%)		3/35 (8.6%)		0/29 (0%)		1/20 (5%)
Sinus congestion	3/29 (10.3%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Sinus disorder	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Tachypnoea	0/29 (0%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Throat irritation	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Upper respiratory tract congestion	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Wheezing	2/29 (6.9%)		4/35 (11.4%)		2/29 (6.9%)		3/20 (15%)
Skin and subcutaneous tissue disorders
Acne	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Alopecia	12/29 (41.4%)		8/35 (22.9%)		13/29 (44.8%)		5/20 (25%)
Blister	2/29 (6.9%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Decubitus ulcer	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		2/20 (10%)
Dermatitis	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Dry skin	3/29 (10.3%)		5/35 (14.3%)		3/29 (10.3%)		0/20 (0%)
Ecchymosis	8/29 (27.6%)		7/35 (20%)		4/29 (13.8%)		0/20 (0%)
Erythema	2/29 (6.9%)		3/35 (8.6%)		8/29 (27.6%)		5/20 (25%)
Hyperhidrosis	4/29 (13.8%)		5/35 (14.3%)		5/29 (17.2%)		2/20 (10%)
Leukocytoclastic vasculitis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Leukoplakia	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Nail disorder	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Night sweats	2/29 (6.9%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Palmar-plantar erythrodysaesthesia syndrome	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Penile ulceration	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Periorbital oedema	1/29 (3.4%)		0/35 (0%)		3/29 (10.3%)		0/20 (0%)
Perivascular dermatitis	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Petechiae	8/29 (27.6%)		11/35 (31.4%)		4/29 (13.8%)		0/20 (0%)
Pigmentation disorder	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Pruritus	5/29 (17.2%)		5/35 (14.3%)		6/29 (20.7%)		1/20 (5%)
Purpura	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Rash	7/29 (24.1%)		8/35 (22.9%)		9/29 (31%)		3/20 (15%)
Rash erythematous	3/29 (10.3%)		1/35 (2.9%)		2/29 (6.9%)		1/20 (5%)
Rash follicular	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Rash generalised	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Rash macular	2/29 (6.9%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Rash maculo-papular	2/29 (6.9%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Rash pruritic	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Red man syndrome	1/29 (3.4%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Scab	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Skin discolouration	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Skin disorder	1/29 (3.4%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Skin exfoliation	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Skin hyperpigmentation	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		0/20 (0%)
Skin Hypopigmentation	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Skin irritation	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Skin lesion	3/29 (10.3%)		2/35 (5.7%)		1/29 (3.4%)		1/20 (5%)
Skin nodule	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Skin reaction	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Skin ulcer	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Urticaria	1/29 (3.4%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Surgical and medical procedures
Sinus operation	1/29 (3.4%)		0/35 (0%)		0/29 (0%)		0/20 (0%)
Vascular disorders
Aortic arteriosclerosis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Arterial disorder	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Deep vein thrombosis	1/29 (3.4%)		2/35 (5.7%)		0/29 (0%)		0/20 (0%)
Flushing	1/29 (3.4%)		2/35 (5.7%)		2/29 (6.9%)		0/20 (0%)
Haematoma	2/29 (6.9%)		2/35 (5.7%)		4/29 (13.8%)		1/20 (5%)
Haemorrhage	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		0/20 (0%)
Hot flush	0/29 (0%)		0/35 (0%)		2/29 (6.9%)		0/20 (0%)
Hypertension	6/29 (20.7%)		4/35 (11.4%)		3/29 (10.3%)		0/20 (0%)
Hypertensive crisis	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Hypotension	11/29 (37.9%)		11/35 (31.4%)		10/29 (34.5%)		6/20 (30%)
Orthostatic hypotension	1/29 (3.4%)		1/35 (2.9%)		2/29 (6.9%)		0/20 (0%)
Pallor	4/29 (13.8%)		3/35 (8.6%)		2/29 (6.9%)		0/20 (0%)
Phlebitis	0/29 (0%)		1/35 (2.9%)		0/29 (0%)		1/20 (5%)
Raynaud's phenomenon	0/29 (0%)		0/35 (0%)		0/29 (0%)		1/20 (5%)
Thrombophlebitis superficial	0/29 (0%)		0/35 (0%)		1/29 (3.4%)		0/20 (0%)
Thrombosis	0/29 (0%)		1/35 (2.9%)		1/29 (3.4%)		1/20 (5%)

Limitations/Caveats

Due to the limited sample size in this study, further study is needed to confirm these results. No statistical testings were performed to compare any of the treatment groups. No p-values or odds ratios were reported.

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Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.