Trial of PXD101 (Belinostat) in Combination With Idarubicin to Treat AML Not Suitable for Standard Intensive Therapy

• ClinicalTrials.gov Identifier: NCT00878722
• Recruitment Status: Completed
• First Posted: April 9, 2009
• Results First Posted: November 13, 2014
• Last Update Posted: July 28, 2015
• Sponsor: Valerio Therapeutics
• Information provided by (Responsible Party): Valerio Therapeutics

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia
• Interventions: Drug: PXD101; Drug: idarubicin
• Enrollment: 41

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description	PXD101 (belinostat) 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Period Title: Overall Study
Started	3	3	3	9	7	3	6	7
Completed	0	0	0	0	0	1	0	0
Not Completed	3	3	3	9	7	2	6	7
Reason Not Completed
Progressive disease	3	3	3	7	7	1	4	3
Death	0	0	0	1	0	1	0	2
Adverse Event	0	0	0	0	0	0	2	0
Withdrawal by Subject	0	0	0	0	0	0	0	2
Relapse	0	0	0	1	0	0	0	0

Baseline Characteristics

Arm/Group Title		Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9	Total
Arm/Group Description		PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	Total of all reporting groups
Overall Number of Baseline Participants		3	3	3	9	7	3	6	7	41
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	3 participants	3 participants	9 participants	7 participants	3 participants	6 participants	7 participants	41 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	1 33.3%	1 33.3%	1 33.3%	3 33.3%	4 57.1%	0 0.0%	3 50.0%	3 42.9%	16 39.0%
	>=65 years	2 66.7%	2 66.7%	2 66.7%	6 66.7%	3 42.9%	3 100.0%	3 50.0%	4 57.1%	25 61.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	3 participants	3 participants	9 participants	7 participants	3 participants	6 participants	7 participants	41 participants
	Female	0 0.0%	3 100.0%	0 0.0%	1 11.1%	4 57.1%	1 33.3%	5 83.3%	2 28.6%	16 39.0%
	Male	3 100.0%	0 0.0%	3 100.0%	8 88.9%	3 42.9%	2 66.7%	1 16.7%	5 71.4%	25 61.0%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose, Dose Limiting Toxicity
Description	DLT (dose limiting toxicities): patients with any of the toxicities: 1.Haematological toxicity is not included in the definition due to bone marrow involvement by the disease except for following grade 4 ANC (absolute neutrophil count) and PLT (platelet count) for 6 weeks with less than 5% blasts in bone marrow. 2.Drug related non hematological Grade 3 or 4 toxicity except alopecia, brief nausea and vomiting, diarrhea, rash, arthralgias and myalgias. Treatment interventions should palliate toxicity symptoms prior to concluding a DLT has occurred (e.g if nausea and vomiting to Grade 3 have been associated with the drug). If despite standard treatment Grade 3 nausea and or vomiting persisted then a DLT was considered to have occurred. Grade 4 diarrhea in spite of standard therapeutic measures was included in DLT definition. 3.Inability to tolerate full dosing cycle due to toxicity or any drug-related adverse event resulting in more than 14 day treatment delay in the next treatment cycle
Time Frame	First Cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description:	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Overall Number of Participants Analyzed	3	3	3	9	7	3	6	7
Measure Type: Number; Unit of Measure: participants
	0	0	0	0	0	0	0	0

2. Primary Outcome

Title	Overall Response
Description	Efficacy measured as Response rate (complete response ([CR] and Complete remission with incomplete recovery of platelets [CRi]) and partial response ([PR])) using the response criteria of the International Working Group (Cheson et al 2003). CR includes CRi, CRc (Cytogenetic complete remission), and CRm (Molecular complete remission).
Time Frame	Throughout study, after each cycle for the first two cycles, then after every second cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description:	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Overall Number of Participants Analyzed	3	3	3	9	7	3	6	7
Measure Type: Number; Unit of Measure: participants
	0	1	1	1	1	1	1	3

3. Secondary Outcome

Title	Time to Response (CR and PR)
Description	Time to response: time in weeks from first treatment to obtainment of the particular response status (CR and PR)
Time Frame	Throughout study, after each cycle for the first two cycles, then after every second cycle

Outcome Measure Data

Analysis Population Description

Time to response was reported among participants who reported response

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description:	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Overall Number of Participants Analyzed	0	1	1	1	1	1	1	3
Median (95% Confidence Interval); Unit of Measure: Weeks
		2.6 [1]; (NA to NA)	7.9 [1]; (NA to NA)	6.0 [1]; (NA to NA)	4.0 [1]; (NA to NA)	1.9 [1]; (NA to NA)	4.0 [1]; (NA to NA)	1.0; (0.6 to 2.1)

[1]

Only 1 patient analyzed

4. Secondary Outcome

Title	Duration of Response (CR and PR)
Description	Duration of Response (CR and PR) in Weeks
Time Frame	Throughout study, after each cycle for the first two cycles, then after every second cycle

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of belinostat and/or idarubicin were included in the full analysis set (FAS). Duration of response was reported among participants who reported response

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description:	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Overall Number of Participants Analyzed	0	1	1	1	1	1	1	3
Mean (Full Range); Unit of Measure: weeks
		26.3	20.6	28.1	5.4	30.3	19.6	4.3; (3 to 6.1)

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival: time in weeks from entry into study until death from any cause. All patients without this endpoint at the time of discontinuation or the end of trial have been censored.
Time Frame	Throughout study, after each cycle for the first two cycles, then after every second cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description:	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Overall Number of Participants Analyzed	0	0	0	3	2	1	0	3
Median (95% Confidence Interval); Unit of Measure: Weeks
				10; (3.0 to 10.3)	4.9; (2.0 to 7.9)	3.7; (3.7 to 3.7)		3.9; (0.7 to 9.9)

6. Secondary Outcome

Title	Relapse-Free Survival
Description	Relapse-free survival: time (weeks) from leukemia-free state to relapse or death from any cause.
Time Frame	Throughout study, after each cycle for the first two cycles, then after every second cycle

Outcome Measure Data

Analysis Population Description

Relapse free survival was reported among participants who reported response

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description:	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Overall Number of Participants Analyzed	0	1	1	1	0	1	0	1
Measure Type: Number; Unit of Measure: Weeks
		26.3	20.6	28.1		30.3		6.1

7. Secondary Outcome

Title	Event-Free Survival
Description	Event-free survival: time (weeks) from entry into study until treatment failure, disease relapse or death from any cause.
Time Frame	Throughout study, after each cycle for the first two cycles, then after every second cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description:	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Overall Number of Participants Analyzed	3	3	3	8	7	3	5	5
Median (95% Confidence Interval); Unit of Measure: Weeks
	5.1; (2.1 to 10.9)	3.1; (1.9 to 28.7)	8.0; (6.7 to 28.3)	6.5; (3.0 to 10.3)	2.0; (0.4 to 7.9)	5.4; (3.4 to 32.1)	5.4; (4.1 to 26.0)	6.4; (0.7 to 9.9)

8. Secondary Outcome

Title	Remission Duration
Description	Remission duration: time (weeks) from date of remission status to disease relapse.
Time Frame	Throughout study, after each cycle for the first two cycles, then after every second cycle

Outcome Measure Data

Analysis Population Description

Remission duration was reported among participants who reported response

Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description:	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
Overall Number of Participants Analyzed	0	1	1	0	1	1	1	1
Mean (95% Confidence Interval); Unit of Measure: Weeks
		26.3 [1]; (NA to NA)	20.6 [1]; (NA to NA)		5.4 [1]; (NA to NA)	30.3 [1]; (NA to NA)	19.6 [1]; (NA to NA)	3.0 [1]; (NA to NA)

[1]

Only 1 patient analyzed

9. Secondary Outcome

Title	Belinostat Cmax
Description	Cmax: Arm A: at Cycle 1 Day 4, Cycle 1 Day 5 Arm B: Cycle 1 Day 1 and Cycle 1 Day 2
Time Frame	Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion

Outcome Measure Data

Analysis Population Description

Results shown for dose level 1000 mg/m2/d

Arm/Group Title	Arm A, Cycle 1 Day 4	Arm A, Cycle 1 Day 5	Arm B, Cycle 1 Day 1 and Day 2
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	18	17	15
Mean (Standard Deviation); Unit of Measure: ng/mL
	38744 (22653)	31952 (16319)	9657 (18859)

10. Secondary Outcome

Title	Belinostat AUC (Area Under Curve)
Description	[Not Specified]
Time Frame	Cycle 1, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion

Outcome Measure Data

Analysis Population Description

Results shown for dose level 1000 mg/m2/d

Arm/Group Title	Arm A, Cycle 1 Day 4	Arm A, Cycle 1 Day 5	Arm B, Cycle 1 Day 1 and Day 2
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	18	17	15
Mean (Standard Deviation); Unit of Measure: ng*hrs/mL
	21850 (10327)	21322 (7516)	172823 (280715)

11. Secondary Outcome

Title	Elimination t½
Description	[Not Specified]
Time Frame	Cycle 1, Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion

Outcome Measure Data

Analysis Population Description

Results shown for dose level 1000 mg/m2/d

Arm/Group Title	Arm A, Cycle 1 Day 4	Arm A, Cycle 1 Day 5	Arm B, Cycle 1 Day 1 and Day 2
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	18	17	15
Mean (Standard Deviation); Unit of Measure: Hours
	12.7 (12.2)	13.1 (10.2)	4.21 (2.66)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
Arm/Group Description	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d	PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d	PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles	PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles
All-Cause Mortality
	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events
	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/3 (66.67%)	2/3 (66.67%)	2/3 (66.67%)	7/9 (77.78%)	2/7 (28.57%)	2/3 (66.67%)	6/6 (100.00%)	6/7 (85.71%)
Blood and lymphatic system disorders
Anaemia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Febrile bone marrow aplasia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/9 (22.22%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Febrile neutropenia † 1	1/3 (33.33%)	0/3 (0.00%)	2/3 (66.67%)	1/9 (11.11%)	1/7 (14.29%)	0/3 (0.00%)	2/6 (33.33%)	3/7 (42.86%)
Leukopenia † 1	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	2/6 (33.33%)	0/7 (0.00%)
Neutropenia † 1	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Ascites † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Diarrhoea † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
General disorders
Pyrexia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Infections and infestations
Anal infection † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Bacterial infection † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Central line infection † 1	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Clostridium bacteraemia † 1	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Clostridium difficile colitis † 1	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Enteritis infectious † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Enterobacter bacteraemia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Enterococcal bacteriaemia † 1	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Fungal infection † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Paronychia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Pneumonia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Pseudomonas infection † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Pulmonary mycosis † 1	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Sepsis † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	1/6 (16.67%)	2/7 (28.57%)
Soft tissue infection † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Injury, poisoning and procedural complications
Lumbar vertebral fracture † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Splenic rupture † 1	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Investigations
Blood creatinine increased † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Electrocardiogram QT prolonged † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Metabolism and nutrition disorders
Hypocalcaemia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Tumor lysis syndrome † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	1/7 (14.29%)
Nervous system disorders
Polyneuropathy † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Renal and urinary disorders
Renal failure † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Respiratory, thoracic and mediastinal disorders
Lung disorder † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Lung infiltration † 1	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Pleural effusion † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Skin and subcutaneous tissue disorders
Rash † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, Meddra
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm A, Step 1	Arm A, Step 2	Arm A, Step 3	Arm A, Step 4	Arm B, Steps 1-6	Arm B, Step 7	Arm B, Step 8	Arm B, Step 9
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/3 (100.00%)	3/3 (100.00%)	3/3 (100.00%)	9/9 (100.00%)	6/7 (85.71%)	3/3 (100.00%)	6/6 (100.00%)	7/7 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	1/3 (33.33%)	1/3 (33.33%)	2/3 (66.67%)	5/9 (55.56%)	2/7 (28.57%)	1/3 (33.33%)	3/6 (50.00%)	2/7 (28.57%)
Coagulopathy † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Erythropenia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Febrile Bone Marrow Aplasia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/9 (22.22%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Leukopenia † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	2/6 (33.33%)	0/7 (0.00%)
Lymphadenopathy † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Neutropenia † 2	0/3 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Splenomegaly † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Spontaneous Hematoma † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Thrombocytopenia † 2	1/3 (33.33%)	2/3 (66.67%)	2/3 (66.67%)	3/9 (33.33%)	3/7 (42.86%)	0/3 (0.00%)	3/6 (50.00%)	4/7 (57.14%)
Thrombotic Microangiopathy † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Febrile neutropenia † 2	1/3 (33.33%)	0/3 (0.00%)	2/3 (66.67%)	2/9 (22.22%)	1/7 (14.29%)	0/3 (0.00%)	2/6 (33.33%)	3/7 (42.86%)
Cardiac disorders
Cardiac Disorder † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Conduction Disorder † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Extrasystoles † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Left ventricular dysfunction † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Myocardial Ischaemia † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Supraventricular extrasystoles † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Sinus tachycardia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	2/7 (28.57%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Congenital, familial and genetic disorders
Antithrombin Iii Deficiency † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Ear and labyrinth disorders
Vertigo † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Eye disorders
Diplopia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Dry eye † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	1/6 (16.67%)	1/7 (14.29%)
Lacrimation increased † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Macular Degeneration † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Retinal Haemorrhage † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Vision Blurred † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Visual Impairment † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Vitreous Detachment † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Gastrointestinal disorders
Abdominal Pain † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	1/7 (14.29%)
Abdominal Pain Upper † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	1/7 (14.29%)
Anal Fissure † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Anal Haemorrhage † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Aphthous Stomatitis † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Ascites † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Constipation † 2	1/3 (33.33%)	1/3 (33.33%)	2/3 (66.67%)	1/9 (11.11%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	2/7 (28.57%)
Diarrhoea † 2	0/3 (0.00%)	2/3 (66.67%)	2/3 (66.67%)	4/9 (44.44%)	2/7 (28.57%)	3/3 (100.00%)	5/6 (83.33%)	7/7 (100.00%)
Dry mouth † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	2/6 (33.33%)	3/7 (42.86%)
Dyspepsia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Dysphagia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	1/7 (14.29%)
Flatulence † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Gastrooesophageal Reflux Disease † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Haemorrhoids † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Inguinal Hernia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Intestinal Haemorrhage † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Mouth Haemorrhage † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Nausea † 2	0/3 (0.00%)	3/3 (100.00%)	2/3 (66.67%)	7/9 (77.78%)	3/7 (42.86%)	3/3 (100.00%)	5/6 (83.33%)	4/7 (57.14%)
Proctalgia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Tongue Blistering † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Tongue Discolouration † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Toothache † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Vomiting † 2	0/3 (0.00%)	3/3 (100.00%)	2/3 (66.67%)	5/9 (55.56%)	2/7 (28.57%)	2/3 (66.67%)	5/6 (83.33%)	5/7 (71.43%)
General disorders
Asthenia † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Catheter Site Erythema † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Catheter Site Inflammation † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Catheter Site Related Reaction † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Chest Pain † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Chills † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	2/9 (22.22%)	1/7 (14.29%)	0/3 (0.00%)	2/6 (33.33%)	0/7 (0.00%)
Face Oedema † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Fatigue † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	4/6 (66.67%)	1/7 (14.29%)
Feeling Cold † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
General Physical Health Deterioration † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Generalised Oedema † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	2/7 (28.57%)
Inflammation † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Influenza Like Illness † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Infusion Site Pain † 2	0/3 (0.00%)	0/3 (0.00%)	2/3 (66.67%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Injection Site Reaction † 2	1/3 (33.33%)	0/3 (0.00%)	2/3 (66.67%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Localised Oedema † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Malaise † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Mucosal Inflammation † 2	0/3 (0.00%)	2/3 (66.67%)	1/3 (33.33%)	2/9 (22.22%)	0/7 (0.00%)	0/3 (0.00%)	2/6 (33.33%)	1/7 (14.29%)
Nodule † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Oedema Peripheral † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	8/9 (88.89%)	2/7 (28.57%)	1/3 (33.33%)	3/6 (50.00%)	4/7 (57.14%)
Pyrexia † 2	0/3 (0.00%)	2/3 (66.67%)	1/3 (33.33%)	6/9 (66.67%)	2/7 (28.57%)	2/3 (66.67%)	1/6 (16.67%)	5/7 (71.43%)
Visceral Oedema † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Hepatobiliary disorders
Jaundice † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Infections and infestations
Anal Infection † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Bacterial Infection † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Bronchopulmonary Aspergillosis † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Central Line Infection † 2	0/3 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Clostridium Bacteriaemia † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Clostridium Difficilie Colitis † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Enteritis Infectious † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Enterobacter Bacteriaemia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Enterococcal Bacteriaemia † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Enterocolitis Infectious † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Fungal Infection † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Fungal Skin Infection † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Herpes Simplex † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Impetigo † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Infection † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	1/7 (14.29%)
Nasopharyngitis † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Oral Fungal Infection † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Oral Herpes † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Paronychia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Pneumonia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Pseudomonas Infection † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Pulmonary Mycosis † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Puncture Site Infection † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Sepsis † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	1/6 (16.67%)	2/7 (28.57%)
Soft Tissue Infection † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Tonsillitis † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Upper Respiratory Tract Infection † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Injury, poisoning and procedural complications
Allergic Transfusion Reaction † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Lumbar Vertebral Fracture † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Muscle Rupture † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Postoperative thrombosis † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Procedural Pain † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Splenic Rupture † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Traumatic Haematoma † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Wound Complication † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Investigations
Alanine Aminotransferase Increased † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Aspartate Aminotransferase Increased † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Blood Bilirubin Increased † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Blood Cholesterol Increased † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Blood Creatinine Increased † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	2/6 (33.33%)	3/7 (42.86%)
Blood Potassium Decreased † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Body Temperature Increased † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Central Venous Pressure Increased † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Electrocardiogram Qt Prolonged † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	2/7 (28.57%)	1/3 (33.33%)	3/6 (50.00%)	1/7 (14.29%)
Gamma-Glutamyltransferase Increased † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Haemoglobin Decreased † 2	0/3 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	2/6 (33.33%)	1/7 (14.29%)
Heart Rate Increased † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
International Normalised Ratio Increased † 1	0/3 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Ph Urine Deacreased † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Platelet Count Decreased † 2	0/3 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Troponin T † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Weight Decreased † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Weight Increased † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	2/7 (28.57%)
White Blood Cell Count Decreased † 2	0/3 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Metabolism and nutrition disorders
Decreased Appetite † 2	0/3 (0.00%)	0/3 (0.00%)	2/3 (66.67%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	2/6 (33.33%)	3/7 (42.86%)
Hyperkalaemia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Hypernatraemia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Hyperuricaemia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Hypoalbuminaemia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	1/7 (14.29%)	1/3 (33.33%)	1/6 (16.67%)	0/7 (0.00%)
Hypocalcaemia † 2	0/3 (0.00%)	2/3 (66.67%)	1/3 (33.33%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	3/6 (50.00%)	5/7 (71.43%)
Hypokalaemia † 2	0/3 (0.00%)	3/3 (100.00%)	1/3 (33.33%)	2/9 (22.22%)	0/7 (0.00%)	1/3 (33.33%)	5/6 (83.33%)	5/7 (71.43%)
Hypomagnesaemia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	1/7 (14.29%)
Hyponatraemia † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	1/6 (16.67%)	0/7 (0.00%)
Hypophosphataemia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	1/6 (16.67%)	0/7 (0.00%)
Malnutrition † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Tumour Lysis Syndrome † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	1/7 (14.29%)
Musculoskeletal and connective tissue disorders
Arthralgia † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Back Pain † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/9 (22.22%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Bone Pain † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Joint Swelling † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Muscle Spasms † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	3/7 (42.86%)
Muscular Weakness † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Musculoskeletal Chest Pain † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Myalgia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Neck Pain † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Pain In Extremity † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/9 (22.22%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Nervous system disorders
Dizziness † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	2/7 (28.57%)
Dysgeusia † 2	0/3 (0.00%)	1/3 (33.33%)	2/3 (66.67%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	3/6 (50.00%)	2/7 (28.57%)
Headache † 2	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	2/6 (33.33%)	2/7 (28.57%)
Lethargy † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Movement Disorder † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Nystagmus † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Paraesthesia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Peripheral Sensory Neuropathy † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Polyneuropathy † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	1/7 (14.29%)
Somnolence † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	1/7 (14.29%)
Syncope † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Psychiatric disorders
Anxiety † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	1/7 (14.29%)
Confusional State † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Depression † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Insomnia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	1/3 (33.33%)	1/6 (16.67%)	0/7 (0.00%)
Sleep Disorder † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Renal and urinary disorders
Chromaturia † 1	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Nocturia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Renal Failure † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Urethral Pain † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Urinary Retention † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Cystitis haemorrhagic † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia † 1	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Bronchitis Chronic † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Cough † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	2/9 (22.22%)	2/7 (28.57%)	1/3 (33.33%)	0/6 (0.00%)	2/7 (28.57%)
Dysphonia † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	1/6 (16.67%)	0/7 (0.00%)
Dyspnoea † 2	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	2/9 (22.22%)	0/7 (0.00%)	0/3 (0.00%)	2/6 (33.33%)	4/7 (57.14%)
Epistaxis † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	2/7 (28.57%)
Hiccups † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Lung Disorder † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Lung Infiltration † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Oropharyngeal Blistering † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Pleural Effusion † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Pulmonary Congestion † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Pulmonary Oedema † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	1/7 (14.29%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Rhinitis Allergic † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia † 1	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Blood Blister † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Dry Skin † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	3/7 (42.86%)
Hyperhidrosis † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	2/9 (22.22%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Night Sweats † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	0/7 (0.00%)
Petechiae † 2	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	2/6 (33.33%)	2/7 (28.57%)
Pruritus † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Rash † 2	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	1/3 (33.33%)	1/6 (16.67%)	2/7 (28.57%)
Social circumstances
Denture Wearer † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	1/7 (14.29%)
Vascular disorders
Flushing † 1	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	1/3 (33.33%)	0/6 (0.00%)	1/7 (14.29%)
Hot Flush † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Hypertension † 2	1/3 (33.33%)	1/3 (33.33%)	0/3 (0.00%)	1/9 (11.11%)	1/7 (14.29%)	1/3 (33.33%)	2/6 (33.33%)	2/7 (28.57%)
Hypotension † 2	1/3 (33.33%)	1/3 (33.33%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Pallor † 2	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	1/6 (16.67%)	0/7 (0.00%)
Phlebitis † 2	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	0/9 (0.00%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
Thrombophlebitis † 1	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/9 (11.11%)	0/7 (0.00%)	0/3 (0.00%)	0/6 (0.00%)	0/7 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0); 2 Term from vocabulary, Meddra

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: PRS Admnistrator Gunilla Emanuelson
• Organization: Topotarget A/S
• Phone: +45 39 17 83 92
• EMail: enquiries@topotarget.com

• Responsible Party: Valerio Therapeutics
• ClinicalTrials.gov Identifier: NCT00878722
• Other Study ID Numbers: PXD101-CLN-15
• First Submitted: April 7, 2009
• First Posted: April 9, 2009
• Results First Submitted: June 27, 2014
• Results First Posted: November 13, 2014
• Last Update Posted: July 28, 2015