Trial Outcomes & Findings for Trial of CPX-351 in Newly Diagnosed Elderly AML Patients (NCT NCT00788892)

NCT ID: NCT00788892

Last Updated: 2018-01-12

Results Overview

Response was defined according to International Working Group Criteria (Cheson, et al. 2003) which requires peripheral blood neutrophils of \>1000/µL and peripheral blood platelets of \>100,000/µL in the absence of bone marrow blasts.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 126 participants
• Primary outcome timeframe: Within 6 weeks of the last induction treatment
• Results posted on: 2018-01-12

Participant Flow

Participant milestones

Measure	Arm A: CPX-351 First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Overall Study STARTED	85	41
Overall Study COMPLETED	36	18
Overall Study NOT COMPLETED	49	23

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of CPX-351 in Newly Diagnosed Elderly AML Patients

Baseline characteristics by cohort

Measure	Arm A: CPX-351 n=85 Participants First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 Participants First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice	Total n=126 Participants Total of all reporting groups
Age, Continuous	67.8 years STANDARD_DEVIATION 4.63 • n=5 Participants	68.2 years STANDARD_DEVIATION 4.88 • n=7 Participants	67.9 years STANDARD_DEVIATION 4.69 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	16 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	25 Participants n=7 Participants	78 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 6 weeks of the last induction treatment

Population: Efficacy Evaluable Analysis Set: All randomized subjects who received at least 1 dose of study drug. One subject who developed Philadelphia chromosome positive disease prior to any efficacy assessment was excluded from the Efficacy Analysis Set.

Response was defined according to International Working Group Criteria (Cheson, et al. 2003) which requires peripheral blood neutrophils of >1000/µL and peripheral blood platelets of >100,000/µL in the absence of bone marrow blasts.

Outcome measures

Measure	Arm A: CPX-351 n=84 Participants First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 Participants First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Number of Participants With Complete Remission	41 Participants	20 Participants

SECONDARY outcome

Timeframe: Following achievement of CR over the study period

Population: Efficacy Evaluable Analysis Set

Remission Duration was assessed from the time measurement criteria for CR were met until the first date that disease relapse was objectively documented or the subject died.

Time to remission was measured from the date of randomization to the time measurement criteria for CR were first met.

Outcome measures

Measure	Arm A: CPX-351 n=84 Participants First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 Participants First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Remission Duration/Time to Remission Remission Duration	275 days Interval 40.0 to 730.0	235 days Interval 36.0 to 703.0
Remission Duration/Time to Remission Time to Remission	49 days Interval 32.0 to 163.0	40 days Interval 21.0 to 89.0

SECONDARY outcome

Timeframe: Up to 1 year from randomization

Population: Efficacy Evaluable Analysis Set

Event-free survival begins from randomization to the date persistent disease is documented or date of relapse after CR, or death, whichever comes first.

Outcome measures

Measure	Arm A: CPX-351 n=84 Participants First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 Participants First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Event Free Survival	161 days Interval 116.0 to 226.0	55 days Interval 34.0 to 205.0

SECONDARY outcome

Timeframe: 1 year

Population: Efficacy Evaluable Analysis Set

Survival defined as the time from randomization to death.

Outcome measures

Measure	Arm A: CPX-351 n=84 Participants First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 Participants First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Overall Survival Rate at 1 Year	39 participants	18 participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Efficacy Evaluable Analysis Set

The rate of patients who underwent stem cell transplant.

Outcome measures

Measure	Arm A: CPX-351 n=84 Participants First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 Participants First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Rate of Stem Cell Transplant	13 Participants	10 Participants

SECONDARY outcome

Timeframe: Day 14 (1st Induction)

Population: Efficacy Evaluable Analysis Set

Bone marrow aplasia was defined as <20% cellularity and 5% blasts in the bone marrow aspiration evaluation.

Outcome measures

Measure	Arm A: CPX-351 n=84 Participants First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 Participants First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Aplasia Rate	55 Participants	15 Participants

Adverse Events

Arm A: CPX-351

Serious events: 47 serious events

Other events: 85 other events

Deaths: 0 deaths

Arm B: Cytarabine + Daunorubicin

Serious events: 16 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm A: CPX-351 n=85 participants at risk First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 participants at risk First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Blood and lymphatic system disorders Anaemia	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Blood and lymphatic system disorders Febrile Neutropenia	10.6% 9/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Blood and lymphatic system disorders Thrombocytopenia	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Angina Pectoris	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Atrial Fibrillation	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Cardiac Arrest	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Cardiac Failure Congestive	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Myocardial Infarction	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Restrictive Cardiomyopathy	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Supraventricular Tachycardia	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Eye disorders Blindness	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Abdominal Pain	3.5% 3/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Gastrointestinal Necrosis	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Ileal Perforation	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Eye disorders Mouth Haemorrhage	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Nausea	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Small Intestinal Obstruction	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Vomiting	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Disease Progression	3.5% 3/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Infusion Related Reaction	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Pain	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Pyrexia	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Hepatobiliary disorders Hyperbilirubinaemia	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Immune system disorders Graft Versus Host Disease	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Bacteraemia	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Catheter Site Cellulitis	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Catheter Site Infection	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Cellulitis	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Clostridium Difficile Colitis	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Device Related Sepsis	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Fungal Infection	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Fungal Retinitis	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Fungal Skin Infection	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Pneumonia	4.7% 4/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Pneumonia Fungal	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Sepsis	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Septic Shock	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations System Mycosis	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Urinary Tract Infection	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Injury, poisoning and procedural complications Brain Herniation	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Injury, poisoning and procedural complications Hip Fracture	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Investigations Blood Creatinine Increased	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute Myeloid Leukaemia	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia Recurrent	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Melanoma In Situ	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Convulsion	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Haemorrhage Intracranial	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Subarachnoid Haemorrhage	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Syncope	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Psychiatric disorders Mental Status Changes	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Psychiatric disorders Psychotic Disorder	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Renal and urinary disorders Nephrogenic Diabetes Insipidus	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Renal and urinary disorders Renal Failure	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Renal and urinary disorders Renal Failure Acute	3.5% 3/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Non-Cardiogenic Pulmonary Oedema	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary Oedema	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Respiratory Arrest	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Respiratory Tract Haemorrhage	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Rash	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Stevens-Johnson Syndrome	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Vascular disorders Hypotension	0.00% 0/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.

Other adverse events

Measure	Arm A: CPX-351 n=85 participants at risk First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Arm B: Cytarabine + Daunorubicin n=41 participants at risk First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice
Blood and lymphatic system disorders Anaemia	3.5% 3/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Blood and lymphatic system disorders Febrile Neutropenia	58.8% 50/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	46.3% 19/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Blood and lymphatic system disorders Neutropenia	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	14.6% 6/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Blood and lymphatic system disorders Thrombocytopenia	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Angina Pectoris	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Atrial Fibrillation	14.1% 12/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Bradycardia	9.4% 8/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Cardiac disorders Tachycardia	12.9% 11/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	17.1% 7/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Eye disorders Conjunctivitis	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Abdominal Distension	12.9% 11/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	14.6% 6/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Abdominal Pain	23.5% 20/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	14.6% 6/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Abdominal Pain Upper	11.8% 10/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Ascites	3.5% 3/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Constipation	50.6% 43/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	56.1% 23/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Diarrhoea	65.9% 56/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	65.9% 27/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Dry Mouth	10.6% 9/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Dyspepsia	12.9% 11/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Dysphagia	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Haemorrhoids	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Mouth Haemorrhage	11.8% 10/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Mouth Ulceration	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Nausea	65.9% 56/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	53.7% 22/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Oral Disorder	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Oral Pain	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Stomatitis	35.3% 30/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	22.0% 9/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Toothache	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Vomiting	27.1% 23/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	29.3% 12/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Asthenia	15.3% 13/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	17.1% 7/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Catheter SIte Erythema	20.0% 17/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	14.6% 6/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Catheter Site Pain	10.6% 9/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Chills	38.8% 33/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	31.7% 13/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Fatigue	41.2% 35/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	29.3% 12/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Gait Disturbance	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Oedema peripheral	51.8% 44/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	43.9% 18/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Oedema	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Pain	10.6% 9/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Pyrexia	30.6% 26/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	34.1% 14/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Hepatobiliary disorders Hyperbilirubinaemia	10.6% 9/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Immune system disorders Drug Hypersensitivity	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Bacteraemia	11.8% 10/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Catheter Site Infection	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Cellulitis	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Clostridium difficile infection	10.6% 9/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Pneumonia	17.6% 15/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	29.3% 12/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Injury, poisoning and procedural complications Transfusion Reaction	11.8% 10/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Investigations Blood Alkaline Phosphate Increased	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Investigations Blood Creatinine Increased	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Investigations Breath Sounds Abnormal	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Investigations Cardiac Murmur	9.4% 8/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Investigations Weight Decreased	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Investigations Weight Increased	9.4% 8/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Metabolism and nutrition disorders Decreased Appetite	40.0% 34/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	39.0% 16/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Metabolism and nutrition disorders Dehydration	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Metabolism and nutrition disorders Fluid Overload	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Metabolism and nutrition disorders Hyperglycaemia	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Metabolism and nutrition disorders Hypokalaemia	24.7% 21/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	34.1% 14/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Metabolism and nutrition disorders Hypomagnesaemia	14.1% 12/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Metabolism and nutrition disorders Hyponatraemia	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Metabolism and nutrition disorders Hypophosphataemia	9.4% 8/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Musculoskeletal and connective tissue disorders Arthralgia	14.1% 12/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Musculoskeletal and connective tissue disorders Muscular Weakness	4.7% 4/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Musculoskeletal and connective tissue disorders Myalgia	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Dizziness	22.4% 19/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	29.3% 12/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Dysgeusia	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Headache	35.3% 30/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	19.5% 8/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Lethargy	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Somnolence	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Syncope	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Nervous system disorders Tremor	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Psychiatric disorders Anxiety	18.8% 16/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	17.1% 7/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Psychiatric disorders Confusional State	14.1% 12/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Psychiatric disorders Depression	11.8% 10/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Psychiatric disorders Hallucination	12.9% 11/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Psychiatric disorders Insomnia	28.2% 24/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Psychiatric disorders Mental Status Change	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Renal and urinary disorders Haematuria	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Renal and urinary disorders Pollakiuria	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Renal and urinary disorders Renal Failure	3.5% 3/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Renal and urinary disorders Renal Failure Acute	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Atelectasis	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Cough	38.8% 33/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Dysphonia	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Dyspnoea	21.2% 18/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Epistaxis	35.3% 30/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	19.5% 8/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Haemoptysis	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Hiccups	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Hypoxia	15.3% 13/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	16.5% 14/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	14.6% 6/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	17.6% 15/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary Oedema	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Rales	11.8% 10/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Tachypnoea	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Respiratory, thoracic and mediastinal disorders Wheezing	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Alopecia	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	22.0% 9/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Dry Skin	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Ecchymosis	9.4% 8/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Erythema	11.8% 10/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	17.1% 7/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Hyperhidrosis	16.5% 14/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Night Sweats	9.4% 8/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Petechiae	32.9% 28/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	12.2% 5/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Pruritus	25.9% 22/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	14.6% 6/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Rash	52.9% 45/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	36.6% 15/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Skin Lesion	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Vascular disorders Hypertension	18.8% 16/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	14.6% 6/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Vascular disorders Hypotension	17.6% 15/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	24.4% 10/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Blood and lymphatic system disorders Increased tendency to bruise	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Gingival bleeding	3.5% 3/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Melaena	2.4% 2/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Gastrointestinal disorders Proctalgia	7.1% 6/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
General disorders Chest pain	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	0.00% 0/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Bacterial disease carrier	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Enterococcal bacteraemia	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Infections and infestations Staphylococcal bacteraemia	14.1% 12/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Musculoskeletal and connective tissue disorders Back pain	12.9% 11/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.2% 7/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	4.9% 2/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Musculoskeletal and connective tissue disorders Neck pain	5.9% 5/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Musculoskeletal and connective tissue disorders Pain in extremity	15.3% 13/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	9.8% 4/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Musculoskeletal and connective tissue disorders Pain in jaw	1.2% 1/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Purpura	4.7% 4/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	7.3% 3/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Rash erythematous	9.4% 8/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	14.6% 6/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.
Skin and subcutaneous tissue disorders Rash maculo-papular	12.9% 11/85 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.	2.4% 1/41 • Assessed during treatment period and recorded and reported any new serious adverse events (up to 30 days after completion of Treatment Period) The Safety Analysis Set included subjects receiving at least 1 dose of study drug and consisted of 126 subjects.

Additional Information

Associate Director, Clinical Trial Disclosure & Transparency

Jazz Pharmaceuticals

Phone: 215-832-3750

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place