Trial Outcomes & Findings for A Study of DSP-7888 Dosing Emulsion in Combination With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Following Initial Therapy (NCT NCT03149003)

NCT ID: NCT03149003

Last Updated: 2023-11-15

Results Overview

The number of participants with dose-limiting toxicity (DLT) who were enrolled into Part 1 - the safety set.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 221 participants
• Primary outcome timeframe: Dose-limiting toxicity will be evaluated and applied from Day 1 through Day 29
• Results posted on: 2023-11-15

Participant Flow

Participant milestones

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Overall Study STARTED	4	109	108
Overall Study COMPLETED	4	108	90
Overall Study NOT COMPLETED	0	1	18

Reasons for withdrawal

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Overall Study Randomized but not treated	0	1	18

Baseline Characteristics

A Study of DSP-7888 Dosing Emulsion in Combination With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Following Initial Therapy

Baseline characteristics by cohort

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=4 Participants Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=109 Participants DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=108 Participants Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Total n=221 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	76 Participants n=7 Participants	74 Participants n=5 Participants	153 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	33 Participants n=7 Participants	34 Participants n=5 Participants	68 Participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	37 Participants n=7 Participants	45 Participants n=5 Participants	85 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	72 Participants n=7 Participants	63 Participants n=5 Participants	136 Participants n=4 Participants
Race/Ethnicity, Customized Native Aboriginal (including First Nations, Metis, Inuit)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	3 Participants n=5 Participants	63 Participants n=7 Participants	67 Participants n=5 Participants	133 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	38 Participants n=7 Participants	36 Participants n=5 Participants	74 Participants n=4 Participants
Race/Ethnicity, Customized Black (including African, Caribbean descent)	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Native Americans or Alaskan Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
HLA Class I Type HLA-A*02 Positive Only	4 Participants n=5 Participants	67 Participants n=7 Participants	61 Participants n=5 Participants	132 Participants n=4 Participants
HLA Class I Type HLA-A*24 Positive Only	0 Participants n=5 Participants	29 Participants n=7 Participants	39 Participants n=5 Participants	68 Participants n=4 Participants
HLA Class I Type Both Positive	0 Participants n=5 Participants	13 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants

PRIMARY outcome

Timeframe: Dose-limiting toxicity will be evaluated and applied from Day 1 through Day 29

Population: Analysis limited to patients enrolled into Part 1 - the safety set.

The number of participants with dose-limiting toxicity (DLT) who were enrolled into Part 1 - the safety set.

Outcome measures

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=4 Participants Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Number of Participants Who Experienced a Dose-limiting Toxicity	0 Participants	—	—

PRIMARY outcome

Timeframe: 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, the study closes, up to 24 months.

Population: Analysis limited to patients randomized into Part 2 - the intent-to-treat set.

The effect of DSP-7888 Dosing Emulsion plus BEV versus BEV alone on the OS of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.

Outcome measures

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=109 Participants DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=108 Participants Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Overall Survival (OS) of Patients With Recurrent or Progressive Glioblastoma Multiforme (GBM) Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone	—	10.2 months Interval 8.2 to 11.4	9.4 months Interval 7.4 to 10.3

SECONDARY outcome

Timeframe: 12 months

Population: Analysis limited to patients randomized into Part 2 - the intent-to-treat set.

The effect of DSP-7888 dosing emulsion plus BEV versus BEV alone on the OS of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.

Outcome measures

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=109 Participants DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=108 Participants Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Overall Survival (OS) of Patients With Recurrent or Progressive Glioblastoma Multiforme (GBM) Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone at 12 Months	—	37.9 percentage of participants Interval 28.7 to 47.0	31.6 percentage of participants Interval 22.9 to 40.7

SECONDARY outcome

Timeframe: The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to 24 months

Population: Analysis limited to patients randomized into Part 2 - the intent-to-treat set.

The effect of DSP-7888 dosing emulsion plus Bevacizumab (BEV) versus BEV alone on the Progression Free Survival (PFS) of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. PFS is defined as the interval between randomization and progression or death from any cause any cause as determined by the central radiology body.

Outcome measures

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=109 Participants DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=108 Participants Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Progression Free Survival (PFS) of Patients With Recurrent or Progressive GBM	—	5.3 months Interval 3.9 to 5.6	3.8 months Interval 3.7 to 5.6

SECONDARY outcome

Timeframe: The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause at 6 months

Population: Analysis limited to patients randomized into Part 2 - the intent-to-treat set.

The effect of DSP-7888 dosing emulsion plus Bevacizumab (BEV) versus BEV alone on the Progression Free Survival (PFS) rate in patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. PFS is defined as the interval between randomization date and progression or death from any cause as determined by the central radiology body. The percentage of patients who achieved PFS at 6 months are summarized.

Outcome measures

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=109 Participants DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=108 Participants Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Progression Free Survival (PFS) Rate in Patients With Recurrent or Progressive GBM at 6 Months	—	36.3 percentage of participants Interval 26.7 to 46.0	35.4 percentage of participants Interval 24.0 to 47.0

SECONDARY outcome

Timeframe: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months

Population: Analysis limited to patients randomized into Part 2 - the intent-to-treat set.

Assessment of the objective response rate (ORR) of DSP-7888 dosing emulsion plus BEV versus BEV alone in patients with recurrent or progressive GBM. The response rate is defined as the percentage of patients exhibiting a response (complete response [CR] plus partial response [PR]) based on the Modified Response Assessment in Neuro-Oncology (RANO) criteria as determined by the central radiology body.

Outcome measures

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=109 Participants DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=108 Participants Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
The Effect of DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone on the Response Rate of Patients With Recurrent or Progressive GBM	—	21.1 percentage of participants Interval 13.9 to 30.0	13.0 percentage of participants Interval 7.3 to 20.8

SECONDARY outcome

Timeframe: From the date of first treatment up to 24 months

Population: Analysis limited to patients randomized into Part 2 - the intent-to-treat set. NE signifies "Not Estimable" in the results.

The effect of DSP-7888 dosing emulsion plus BEV versus BEV alone on the duration of response of patients with recurrent or progressive GBM. The duration of response is defined as the interval between first documented oncological response and progression of disease or death from any cause.

Outcome measures

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=109 Participants DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=108 Participants Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Duration of Response in Patients With Recurrent or Progressive GBM Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone	—	4.81 months Standard Deviation 7.119	3.69 months Standard Deviation 4.017

SECONDARY outcome

Timeframe: The time from the date of first treatment, while the patient is on treatment, and for 30 days after stopping therapy, an average of 4 months

Assessment of safety of DSP7888 dosing emulsion plus Bevacizumab (BEV) versus BEV alone in patients with recurrent or progressive GBM

Outcome measures

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=4 Participants Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=109 Participants DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=108 Participants Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Number of Participants With Adverse Events and Serious Adverse Events	4 Participants	106 Participants	79 Participants

Adverse Events

Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab

Serious events: 1 serious events

Other events: 4 other events

Deaths: 4 deaths

Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab

Serious events: 10 serious events

Other events: 106 other events

Deaths: 96 deaths

Part 2 - Arm 2: Bevacizumab

Serious events: 6 serious events

Other events: 79 other events

Deaths: 89 deaths

Serious adverse events

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=4 participants at risk Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=108 participants at risk DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=90 participants at risk Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Nervous system disorders Seizure	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 6/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 5/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Cerebrovascular accident	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	2.2% 2/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Encephalopathy	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.9% 2/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Hydrocephalus	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.9% 2/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Cerebral haemorrhage	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Asthenia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	3.7% 4/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Gait disturbance	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.9% 2/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Infections and infestations Sepsis	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.9% 2/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.9% 2/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Cardiac disorders Atrial fibrillation	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.9% 2/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Investigations Alanine aminotransferase increased	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	2.2% 2/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Headache	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Intracranial venous sinus thrombosis	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Putamen haemorrhage	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Hypertensive encephalopathy	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Vascular disorders Embolism	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Vascular disorders Hypertension	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Vascular disorders Hypertensive crisis	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Death	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Infections and infestations Wound infection pseudomonas	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Injury, poisoning and procedural complications Wound complication	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Gastrointestinal disorders Haematochezia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.

Other adverse events

Measure	Part 1 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=4 participants at risk Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Name: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Name: Avastin	Part 2 - Arm 1: DSP-7888 Dosing Emulsion Plus Bevacizumab n=108 participants at risk DSP-7888 Dosing Emulsion: DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.	Part 2 - Arm 2: Bevacizumab n=90 participants at risk Bevacizumab: Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.
Gastrointestinal disorders Vomiting	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	13.9% 15/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.7% 6/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	11.1% 12/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	12.2% 11/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Gastrointestinal disorders Dry mouth	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Gastrointestinal disorders Dysphagia	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.9% 2/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	2.2% 2/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Gastrointestinal disorders Gastrooesophageal reflux disease	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Gastrointestinal disorders Nausea	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	12.0% 13/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	16.7% 15/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Injection site reaction	75.0% 3/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	81.5% 88/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Fatigue	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	29.6% 32/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	18.9% 17/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Pyrexia	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	13.0% 14/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.8% 7/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Injection site erythema	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Oedema peripheral	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.4% 8/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 5/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Headache	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	36.1% 39/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	25.6% 23/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Seizure	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	20.4% 22/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	11.1% 10/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Brain oedema	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Dizziness	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 6/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.8% 7/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Hemiparesis	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	9.3% 10/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	8.9% 8/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Metabolism and nutrition disorders Decreased appetite	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	13.0% 14/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 5/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Metabolism and nutrition disorders Hypomagnesaemia	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	2.8% 3/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Psychiatric disorders Anxiety	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	4.6% 5/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.8% 7/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Psychiatric disorders Confusional state	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	13.9% 15/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.7% 6/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Psychiatric disorders Insomnia	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	9.3% 10/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	10.0% 9/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Psychiatric disorders Mental status changes	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Psychiatric disorders Psychotic disorder	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Cough	75.0% 3/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	13.9% 15/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	2.2% 2/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	4.6% 5/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 5/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Stridor	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Skin and subcutaneous tissue disorders Alopecia	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Skin and subcutaneous tissue disorders Hyperhidrosis	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Blood and lymphatic system disorders Thrombocytopenia	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.93% 1/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Ear and labyrinth disorders Hyperacusis	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Endocrine disorders Adrenal insufficiency	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	0.00% 0/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Vascular disorders Hypertension	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	37.0% 40/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	26.7% 24/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Gait disturbance	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	9.3% 10/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	8.9% 8/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
General disorders Asthenia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 6/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 5/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Aphasia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	14.8% 16/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	12.2% 11/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Nervous system disorders Memory impairment	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	9.3% 10/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	4.4% 4/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Gastrointestinal disorders Constipation	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	20.4% 22/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	12.2% 11/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.5% 7/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	2.2% 2/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Infections and infestations Urinary tract infection	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	13.9% 15/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.7% 6/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	11.1% 12/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	3.3% 3/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	9.3% 10/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	10.0% 9/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	8.3% 9/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	2.2% 2/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.4% 8/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	3.3% 3/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.5% 7/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 6/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.8% 7/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Psychiatric disorders Depression	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.4% 8/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	4.4% 4/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.5% 7/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.8% 7/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	8.3% 9/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.7% 6/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.5% 7/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	4.6% 5/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.7% 6/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Renal and urinary disorders Proteinuria	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	17.6% 19/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	10.0% 9/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Renal and urinary disorders Urinary incontinence	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.5% 7/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	1.1% 1/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Investigations Weight decreased	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	9.3% 10/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	3.3% 3/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Investigations Lymphocyte count decreased	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	7.4% 8/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	2.2% 2/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Investigations Alanine aminotransferase increased	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.5% 7/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	10.0% 9/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Investigations Aspartate aminotransferase increased	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 6/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	6.7% 6/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Investigations Weight increased	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	4.6% 5/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	5.6% 5/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.
Injury, poisoning and procedural complications Fall	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	18.5% 20/108 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.	11.1% 10/90 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 24 months. In part 2 of the trial, 109 patients were randomized to arm 1, however 1 patient did not receive study drug and did not complete the trial. Therefore, the 108 patients in arm 1 who were randomized and received study drug were at risk for AEs or SAEs. In part 2 - arm 2, 108 patients were randomized, however 18 patients did not receive study drug and did not complete the trial. Therefore, the 90 patients in arm 2 who were randomized and received study drug were at risk for AEs or SAEs.

Additional Information

Sheila Dhaskali

Sumitomo Pharma Oncology

Phone: 617-674-6800

Email: Sheila.dhaskali@oncology.sumitomo-pharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institution shall submit to Sponsor for its review a copy of any proposed publication resulting from the study at least thirty days prior to the date of submission for publication. Sponsor shall complete its review within thirty days of its receipt of the proposed publication.
• Publication restrictions are in place

Restriction type: OTHER