Trial Outcomes & Findings for Lapatinib in Combination With Weekly Paclitaxel in Patients With ErbB2 Amplified Advanced Gastric Cancer (NCT NCT00486954)

NCT ID: NCT00486954

Last Updated: 2013-06-20

Results Overview

DLTs consisted of only drug-related toxicities (neurologic and non-neurologic DLTs). A neurologic DLT was defined as grade 3/4 clinically significant peripheral motor and/or sensitive neuropathy. Non-neurologic DLTs mainly included the following: grade 3/4 clinically significant non-hematological toxicity (except nausea), grade 4 neutropenia lasting \>=7 days, thrombocytopenia (\<=25000 cells per cubic millimeter), inability to begin next treatment within 2 weeks of scheduled dosing due to unresolved toxicity, treatment delay (due to toxicity) of \>5 days, for Days 8 or 15 of weekly paclitaxel.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 273 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2013-06-20

Participant Flow

This study consisted of a Pilot part and a Randomized part. The Pilot part and the Randomized part had two separate participant (par.) populations. The study period of the Randomized part was from 31 March 2008 to 5 January 2012 (cut-off date for efficacy). Follow-up was conducted until 30 October 2012 (cut-off date for safety analysis).

In the Pilot part, par. were enrolled in this study based on their gastrectomy status: non-gastrectomy (intact stomach), partial gastrectomy (gastrectomy with pylorus preserved), and gastrectomy (pylorus removed). However, no par. with partial gastrectomy were enrolled. In the Randomized part, par. were randomized to two treatment arms.

Participant milestones

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Partial Gastrectomy Participants Participants with partial gastrectomy (which includes preservation of the pylorus) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2. Partial gastrectomy (pylorus preserved) is very rare population in Japan. As a result, no such participants were recruited into this cohort.	Lapatinib Plus Paclitaxel in Gastrectomy Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.	Lapatinib Plus Paclitaxel Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).	Paclitaxel Alone Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).
Pilot Part STARTED	6	0	6	0	0
Pilot Part COMPLETED	0	0	0	0	0
Pilot Part NOT COMPLETED	6	0	6	0	0
Randomized Part STARTED	0	0	0	132	129
Randomized Part COMPLETED	0	0	0	112	115
Randomized Part NOT COMPLETED	0	0	0	20	14

Reasons for withdrawal

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Partial Gastrectomy Participants Participants with partial gastrectomy (which includes preservation of the pylorus) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2. Partial gastrectomy (pylorus preserved) is very rare population in Japan. As a result, no such participants were recruited into this cohort.	Lapatinib Plus Paclitaxel in Gastrectomy Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.	Lapatinib Plus Paclitaxel Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).	Paclitaxel Alone Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).
Pilot Part Adverse Event	4	0	5	0	0
Pilot Part Disease Progression	2	0	1	0	0
Randomized Part Lost to Follow-up	0	0	0	0	1
Randomized Part Withdrawal by Subject	0	0	0	1	0
Randomized Part Sponsor Terminated Study	0	0	0	19	13

Baseline Characteristics

Lapatinib in Combination With Weekly Paclitaxel in Patients With ErbB2 Amplified Advanced Gastric Cancer

Baseline characteristics by cohort

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants In the Pilot part, participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants In the Pilot part, participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.	Lapatinib Plus Paclitaxel in Randomized Part n=132 Participants Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).	Paclitaxel Alone in Randomized Part n=129 Participants Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).	Total n=273 Participants Total of all reporting groups
Age Continuous	57.5 Years STANDARD_DEVIATION 11.31 • n=5 Participants	57.2 Years STANDARD_DEVIATION 10.98 • n=7 Participants	60.8 Years STANDARD_DEVIATION 9.45 • n=5 Participants	60.4 Years STANDARD_DEVIATION 10.96 • n=4 Participants	60.5 Years STANDARD_DEVIATION 10.23 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	31 Participants n=5 Participants	23 Participants n=4 Participants	55 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	101 Participants n=5 Participants	106 Participants n=4 Participants	218 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	6 Participants n=5 Participants	6 Participants n=7 Participants	52 Participants n=5 Participants	48 Participants n=4 Participants	112 Participants n=21 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	73 Participants n=5 Participants	75 Participants n=4 Participants	148 Participants n=21 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants	6 Participants n=4 Participants	13 Participants n=21 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Safety Population (Pilot part): all participants who received at least one dose of investigational product in the Pilot part of the study

DLTs consisted of only drug-related toxicities (neurologic and non-neurologic DLTs). A neurologic DLT was defined as grade 3/4 clinically significant peripheral motor and/or sensitive neuropathy. Non-neurologic DLTs mainly included the following: grade 3/4 clinically significant non-hematological toxicity (except nausea), grade 4 neutropenia lasting >=7 days, thrombocytopenia (<=25000 cells per cubic millimeter), inability to begin next treatment within 2 weeks of scheduled dosing due to unresolved toxicity, treatment delay (due to toxicity) of >5 days, for Days 8 or 15 of weekly paclitaxel.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study	2 Participants	1 Participants

PRIMARY outcome

Timeframe: From randomization until death due to any cause (up to 42.58 months)

Population: Intent-to-Treat Population: all participants who were randomized to study treatment, regardless of whether they actually received study medication

OS was defined as the time from randomization until death due to any cause. For participants who did not die, time to death was censored at the time of last contact. For censored participants, time to death was defined as the time from randomization to the time of last contact.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=132 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=129 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Overall Survival (OS) in the Randomized Part of the Study	11.0 months Interval 9.5 to 14.5	8.9 months Interval 7.4 to 11.1

SECONDARY outcome

Timeframe: Days 8 and 14

Population: PK Parameter Population: all participants for whom the PK parameter could be estimated

Pharmacokinetic (PK) samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study Day 8	5435.525 nanograms per milliliter (ng/mL) Interval 3932.949 to 7512.158	3129.561 nanograms per milliliter (ng/mL) Interval 2429.401 to 4031.507
Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study Day 14	3930.780 nanograms per milliliter (ng/mL) Interval 3239.218 to 4769.988	2062.557 nanograms per milliliter (ng/mL) Interval 1301.258 to 3269.251

SECONDARY outcome

Timeframe: Days 8 and 14

Population: PK Parameter Population

PK samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study Day 8	4.083 hours (hr) Interval 2.98 to 8.0	3.500 hours (hr) Interval 2.97 to 6.05
Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study Day 14	7.992 hours (hr) Interval 3.1 to 11.97	4.000 hours (hr) Interval 3.03 to 4.08

SECONDARY outcome

Timeframe: Days 8 and 14

Population: PK Parameter Population

PK samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14. AUC is defined as the area under the lapatinib concentration-time curve as a measure of drug exposure. AUC(0-24) is area under the plasma concentration-time curve from time 0 to 24 hours after oral adminisation.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study Day 8	86584.045 hr*ng/mL Interval 71317.921 to 105117.994	37332.880 hr*ng/mL Interval 27185.084 to 51268.7
Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study Day 14	68177.402 hr*ng/mL Interval 54550.364 to 85208.564	30565.248 hr*ng/mL Interval 18109.123 to 51589.156

SECONDARY outcome

Timeframe: Days 1 and 8

Population: PK Parameter Population

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Cmax of Paclitaxel in the Pilot Part of the Study Day 1	4121.513 ng/mL Interval 3524.391 to 4819.803	2731.104 ng/mL Interval 2275.497 to 3277.934
Cmax of Paclitaxel in the Pilot Part of the Study Day 8	4610.176 ng/mL Interval 3896.911 to 5453.992	2949.770 ng/mL Interval 2695.77 to 3227.702

SECONDARY outcome

Timeframe: Days 1 and 8

Population: PK Parameter Population

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Tmax of Paclitaxel in the Pilot Part of the Study Day 1	1.042 hr Interval 1.0 to 1.42	1.075 hr Interval 0.98 to 1.25
Tmax of Paclitaxel in the Pilot Part of the Study Day 8	1.050 hr Interval 1.0 to 1.18	1.025 hr Interval 1.0 to 1.07

SECONDARY outcome

Timeframe: Days 1 and 8

Population: PK Parameter Population

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. AUC is defined as the area under the paclitaxel concentration-time curve as a measure of drug exposure. AUC(0-24) is area under the plasma concentration-time curve from the start of infusion (time 0) to 24 hours after the start of the infusion.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
AUC(0-24) of Paclitaxel in the Pilot Part of the Study Day 1	5771.847 hr*ng/mL Interval 4726.425 to 7048.502	3968.654 hr*ng/mL Interval 3531.979 to 4459.317
AUC(0-24) of Paclitaxel in the Pilot Part of the Study Day 8	7492.825 hr*ng/mL Interval 6182.574 to 9080.754	4992.934 hr*ng/mL Interval 4432.158 to 5624.66

SECONDARY outcome

Timeframe: Days 1 and 8

Population: PK Parameter Population

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. AUC is defined as the area under the paclitaxel concentration-time curve as a measure of drug exposure. AUC(0-inf) is area under the plasma concentration-time curve from the start of infusion (time 0) extrapolated to infinity.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study Day 1	6262.157 hr*ng/mL Interval 5042.138 to 7777.378	4058.648 hr*ng/mL Interval 3952.209 to 5143.429
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study Day 8	8340.326 hr*ng/mL Interval 6835.815 to 10175.97	6020.878 hr*ng/mL Interval 4347.656 to 8338.049

SECONDARY outcome

Timeframe: Days 1 and 8

Population: PK Parameter Population

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Half-life is defined as the time required for the amount of the drug in the plasma to decrease by half.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Half-life of Paclitaxel in the Pilot Part of the Study Day 1	10.128 hr Interval 8.886 to 11.543	13.053 hr Interval 10.266 to 16.597
Half-life of Paclitaxel in the Pilot Part of the Study Day 8	10.342 hr Interval 8.46 to 12.642	13.978 hr Interval 7.748 to 25.219

SECONDARY outcome

Timeframe: Days 1 and 8

Population: PK Parameter Population

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Clearance is defined as the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Clearance of Paclitaxel in the Pilot Part of the Study Day 1	12.775 liters per hour per square meter Interval 10.286 to 15.866	17.744 liters per hour per square meter Interval 15.554 to 20.242
Clearance of Paclitaxel in the Pilot Part of the Study Day 8	9.592 liters per hour per square meter Interval 7.862 to 11.703	13.287 liters per hour per square meter Interval 9.595 to 18.401

SECONDARY outcome

Timeframe: Days 1 and 8

Population: PK Parameter Population

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Vss is the volume of distribution at steady state of paclitaxel.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study Day 8	71.223 liters per square meter Interval 55.644 to 91.163	126.121 liters per square meter Interval 79.776 to 199.391
Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study Day 1	76.011 liters per square meter Interval 67.17 to 86.015	141.196 liters per square meter Interval 110.329 to 180.698

SECONDARY outcome

Timeframe: From randomization until disease progression or death due to any cause (up to 42.35 months)

Population: ITT Population. For participants whose disease did not progress or who did not die, PFS was censored at the time of the last independently assessed radiological scan preceding the initiation of any alternate anti-cancer therapy.

PFS was defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0, PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=132 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=129 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Progression-free Survival (PFS) in the Randomized Part of the Study	5.4 months Interval 3.9 to 5.7	4.4 months Interval 3.7 to 5.6

SECONDARY outcome

Timeframe: From randomization until disease progression or death due to disease (up to 42.35 months )

Population: ITT Population

Time to progression was defined as the time from randomization until the earliest date of disease progression or death due to disease. Per RECIST, version 1.0, PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=132 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=129 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Time to Progression in the Randomized Part of the Study	5.5 months Interval 3.9 to 5.8	4.4 months Interval 3.7 to 5.6

SECONDARY outcome

Timeframe: From randomization up to 5.62 months

Population: ITT Population

Overall response was defined as the percentage of participants achieving either complete response (CR) or partial response (PR). Per RECIST, version 1.0, CR was defined as the disappearance of all target lesions, and PR was defined as a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=132 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=129 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Percentage of Participants With Overall Response in the Randomized Part of the Study	27 Percentage of participants	9 Percentage of participants

SECONDARY outcome

Timeframe: up to 5.62 months

Population: ITT Population. Only those participants achieving a CR or PR were assessed.

Time to response was defined as the time from randomization to CR (the disappearance of all target lesions) or PR (a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD). For participants who did not achieve a CR or PR, time to response was censored at the last assessment prior to other cancer therapies. For censored participants, time to response was defined as the time from randomization to the time of the last assessment prior to the administation of other cancer therapies.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=35 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=11 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Number of Participants With the Indicated Time to Response in the Randomized Part of the Study Weeks 1-8	13 Participants	5 Participants
Number of Participants With the Indicated Time to Response in the Randomized Part of the Study Weeks >8 - 16	20 Participants	3 Participants
Number of Participants With the Indicated Time to Response in the Randomized Part of the Study Weeks >16 - 24	1 Participants	3 Participants
Number of Participants With the Indicated Time to Response in the Randomized Part of the Study Weeks >24 - 32	1 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 18.27 months

Population: ITT Population. Only those participants achieving a CR or PR were assessed.

Duration of response was defined as the time from the first documented evidence of CR (the disappearance of all target lesions) or PR (a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD) until the first documented sign of disease progression (at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions) or death due to any cause, if sooner.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=35 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=11 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Duration of Response in the Randomized Part of the Study	7.4 months Interval 5.0 to 11.0	5.1 months Interval 3.7 to 11.2

SECONDARY outcome

Timeframe: From the first dose of investigational product to 30 days after the last dose (up to 110.3 weeks in the Randomized part)

Population: Safety Population: all participants who were randomized and took at least one dose of study medication

The Common Terminology Criteria for Advere Events (CTCAE) is a descriptive terminology that can be used for AE reporting. Grade (G) refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade (G) refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=131 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=129 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Abdominal pain, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Peripheral sensory neuropathy, G 3	1 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Diarrhoea, Grade 3	23 participants	3 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Diarrhoea, Grade 4	1 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Nausea, Grade 3	5 participants	3 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Nausea, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Vomiting, Grade 3	4 participants	4 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Vomiting, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Stomatitis, Grade 3	2 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Stomatitis, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Constipation, Grade 3	0 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Constipation, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Abdominal pain, Grade 3	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Neutropenia, Grade 3	41 participants	33 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Neutropenia, Grade 4	34 participants	6 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Leukopenia, Grade 3	32 participants	12 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Leukopenia, Grade 4	7 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Anaemia, Grade 3	10 participants	8 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Anaemia, Grade 4	4 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Lymphopenia, Grade 3	4 participants	2 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Lymphopenia, Grade 4	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Alopecia, Grade 3	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Alopecia, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Rash, Grade 3	3 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Rash, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Pruritus, Grade 3	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Pruritus, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Fatigue, Grade 3	6 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Fatigue, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Pyrexia, Grade 3	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Pyrexia, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Asthenia, Grade 3	1 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Asthenia, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Weight decreased, Grade 3	2 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Weight decreased, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Peripheral sensory neuropathy, G 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study White blood cell count decreased, Grade 3	18 participants	6 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study White blood cell count decreased, Grade 4	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Neutrophil count decreased, Grade 3	11 participants	4 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Neutrophil count decreased, Grade 4	5 participants	2 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Haemoglobin decreased, Grade 3	9 participants	5 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Haemoglobin decreased, Grade (G) 4	1 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Aspartate aminotransferase increased, G 3	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Aspartate aminotransferase increased, G 4	1 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Alanine aminotransferase increased, G 3	2 participants	2 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Alanine aminotransferase increased, G 4	1 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Neuropathy peripheral, Grade 3	2 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Neuropathy peripheral, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Decreased appetite, Grade 3	11 participants	9 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Decreased appetite, Grade 4	1 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Myalgia, Grade 3	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Myalgia, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Arthralgia, Grade 3	2 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Arthralgia, Grade 4	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Back pain, Grade 3	0 participants	0 participants
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study Back pain, Grade 4	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=70 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QOL Score at the End of Therapy in the Randomized Part of the Study	-12.41 scores on a scale Standard Deviation 25.578	-11.55 scores on a scale Standard Deviation 28.562

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score at the End of Therapy in the Randomized Part of the Study	-13.48 scores on a scale Standard Deviation 18.776	-13.99 scores on a scale Standard Deviation 21.087

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Role Functioning Score at the End of Therapy in the Randomized Part of the Study	-17.41 scores on a scale Standard Deviation 24.468	-18.31 scores on a scale Standard Deviation 27.625

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=70 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score at the End of Therapy in the Randomized Part of the Study	-10.65 scores on a scale Standard Deviation 19.594	-10.12 scores on a scale Standard Deviation 22.066

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=70 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Score at the End of Therapy in the Randomized Part of the Study	-10.19 scores on a scale Standard Deviation 16.133	-12.14 scores on a scale Standard Deviation 20.446

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=70 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Social Functioning Score at the End of Therapy in the Randomized Part of the Study	-10.74 scores on a scale Standard Deviation 26.122	-13.33 scores on a scale Standard Deviation 22.089

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Fatigue Symptom Score at the End of Therapy in the Randomized Part of the Study	11.98 scores on a scale Standard Deviation 21.084	14.79 scores on a scale Standard Deviation 23.885

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Symptom Score at the End of Therapy in the Randomized Part of the Study	4.26 scores on a scale Standard Deviation 17.411	7.28 scores on a scale Standard Deviation 19.666

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Pain Symptom Score at the End of Therapy in the Randomized Part of the Study	7.41 scores on a scale Standard Deviation 27.038	12.68 scores on a scale Standard Deviation 29.743

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Dyspnea Symptom Score at the End of Therapy in the Randomized Part of the Study	12.22 scores on a scale Standard Deviation 22.037	15.02 scores on a scale Standard Deviation 23.764

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Insomnia Symptom Score at the End of Therapy in the Randomized Part of the Study	5.56 scores on a scale Standard Deviation 28.813	10.80 scores on a scale Standard Deviation 27.473

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Symptom Score at the End of Therapy in the Randomized Part of the Study	12.59 scores on a scale Standard Deviation 28.521	7.04 scores on a scale Standard Deviation 28.683

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Constipation Symptom Score at the End of Therapy in the Randomized Part of the Study	5.93 scores on a scale Standard Deviation 27.176	2.35 scores on a scale Standard Deviation 26.621

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=70 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Diarrhea Symptom Score at the End of Therapy in the Randomized Part of the Study	10.00 scores on a scale Standard Deviation 31.385	4.29 scores on a scale Standard Deviation 24.025

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales [physical/role/emotional/cognitive/social]; 9 symptom scales [fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=70 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Symptom Score at the End of Therapy in the Randomized Part of the Study	7.04 scores on a scale Standard Deviation 28.042	0.95 scores on a scale Standard Deviation 27.200

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Dysphagia Scale Score at the End of Therapy in the Randomized Part of the Study	10.37 scores on a scale Standard Deviation 21.382	5.16 scores on a scale Standard Deviation 14.887

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Pain Scale Score at the End of Therapy in the Randomized Part of the Study	5.46 scores on a scale Standard Deviation 16.151	3.40 scores on a scale Standard Deviation 14.542

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Reflux Symptoms Scale Score at the End of Therapy in the Randomized Part of the Study	3.33 scores on a scale Standard Deviation 14.177	2.66 scores on a scale Standard Deviation 15.312

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Eating Restrictions Scale Score at the End of Therapy in the Randomized Part of the Study	8.33 scores on a scale Standard Deviation 18.780	6.69 scores on a scale Standard Deviation 18.720

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Anxiety Scale Score at the End of Therapy in the Randomized Part of the Study	8.27 scores on a scale Standard Deviation 24.624	2.97 scores on a scale Standard Deviation 21.899

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Dry Mouth Scale Score at the End of Therapy in the Randomized Part of the Study	8.15 scores on a scale Standard Deviation 27.053	2.35 scores on a scale Standard Deviation 21.324

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Taste Scale Score at the End of Therapy in the Randomized Part of the Study	13.70 scores on a scale Standard Deviation 28.659	3.29 scores on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=90 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=71 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Body Image Scale Score at the End of Therapy in the Randomized Part of the Study	15.99 scores on a scale Standard Deviation 27.442	8.45 scores on a scale Standard Deviation 32.229

SECONDARY outcome

Timeframe: Baseline and end of therapy (up to 42.58 months)

Population: ITT Population. Only those participants who contributed data were analyzed.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=22 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=13 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Change From Baseline in the EORTC QLQ-STO22 Hair Loss Scale Score at the End of Therapy in the Randomized Part of the Study	9.09 scores on a scale Standard Deviation 31.171	7.69 scores on a scale Standard Deviation 33.758

SECONDARY outcome

Timeframe: Pretreatment

Population: ITT Population. Only those participants for whom immunohistochemistry testing was conducted were analyzed.

EGFR protein expression on the surface of cells in gastric cancer tissue samples was measured using a moncolonal antibody specific for the extracellular region of EGFR, and the degree of membrane staining was evaluated. 3+ indicates positive EGFR expression; <3+ indicates negative EGFR expression.

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=73 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=65 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study <3+	68 participants	59 participants
Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study 3+	5 participants	6 participants

SECONDARY outcome

Timeframe: Pretreatment

Population: ITT Population. Only those participants for whom immunohistochemistry testing was conducted were analyzed.

HER2 protein expression on the surface of cells in gastric cancer tissue samples was measured using a monoclonal antibody specific for the extracellulr region of HER2, and the degree of membrane staining was evaulated. The immunohistochemistry test gives a score of 0 to 3+ and measures the amount of HER2 receptor protein on the surface of cells in a gastric cancer tissue sample. Score of 0 to 1+, "HER2 negative"; score of 2+, "borderline"; score of 3+, "HER2 positive."

Outcome measures

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=100 Participants Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=92 Participants Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.
Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study 0/1+	36 participants	32 participants
Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study 2+	12 participants	11 participants
Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study 3+	52 participants	49 participants

SECONDARY outcome

Timeframe: Pretreatment

Population: ITT Population

An inadequate number of tissue samples were obtained; thus, analysis could not be performed.

Outcome measures

Outcome data not reported

Adverse Events

Lapatinib Plus Paclitaxel in Non-gastrectomy Participants

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Lapatinib Plus Paclitaxel in Gastrectomy Participants

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Lapatinib Plus Paclitaxel in Randomized Part

Serious events: 38 serious events

Other events: 131 other events

Deaths: 0 deaths

Paclitaxel Alone in Randomized Part

Serious events: 20 serious events

Other events: 126 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 participants at risk In the Pilot part, participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 participants at risk In the Pilot part, participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.	Lapatinib Plus Paclitaxel in Randomized Part n=131 participants at risk Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).	Paclitaxel Alone in Randomized Part n=129 participants at risk Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).
Infections and infestations Pneumonia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.1% 4/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Decreased appetite	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.8% 5/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Enterocolitis infectious	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Musculoskeletal and connective tissue disorders Back pain	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Beta haemolytic streptococcal infection	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Pyrexia	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Peripheral sensory neuropathy	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Ileus	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Constipation	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Gastrointestinal obstruction	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Gastrointestinal perforation	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Ileus paralytic	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Melaena	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Subileus	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Device related infection	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Herpes zoster	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Infection	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Cellulitis	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Cholangitis suppurative	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Pneumonia pneumococcal	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Sepsis	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.1% 8/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Blood and lymphatic system disorders Neutropenia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.1% 4/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Blood and lymphatic system disorders Leukopenia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Asthenia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Death	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Oedema peripheral	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Cardiac disorders Acute left ventricular failure	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Cardiac disorders Acute myocardial infarction	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Cardiac disorders Cardiac arrest	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Cardiac disorders Left ventricular dysfunction	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Vascular disorders Deep vein thrombosis	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Vascular disorders Embolism	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Endocrine disorders Hypothyroidism	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Eye disorders Cataract	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Haemoglobin decreased	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Cerebral infarction	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Nausea	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.

Other adverse events

Measure	Lapatinib Plus Paclitaxel in Non-gastrectomy Participants n=6 participants at risk In the Pilot part, participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).	Lapatinib Plus Paclitaxel in Gastrectomy Participants n=6 participants at risk In the Pilot part, participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.	Lapatinib Plus Paclitaxel in Randomized Part n=131 participants at risk Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).	Paclitaxel Alone in Randomized Part n=129 participants at risk Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).
Blood and lymphatic system disorders Neutropenia	100.0% 6/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	83.3% 5/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	64.9% 85/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	49.6% 64/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Blood and lymphatic system disorders Anaemia	83.3% 5/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	34.4% 45/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	20.9% 27/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Blood and lymphatic system disorders Leukopenia	83.3% 5/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	66.7% 4/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	51.1% 67/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	41.9% 54/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Blood and lymphatic system disorders Lymphopenia	83.3% 5/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	13.0% 17/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	11.6% 15/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Blood and lymphatic system disorders Monocytopenia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Nausea	100.0% 6/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	35.1% 46/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	27.1% 35/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Diarrhoea	83.3% 5/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	83.3% 5/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	76.3% 100/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	22.5% 29/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Stomatitis	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	31.3% 41/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	14.0% 18/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Vomiting	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	29.0% 38/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	17.8% 23/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Abdominal discomfort	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	4.6% 6/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Abdominal distension	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.1% 8/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.4% 7/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Anal haemorrhage	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Cheilitis	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.8% 5/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Gastric ulcer	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Constipation	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	11.5% 15/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	20.2% 26/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	13.0% 17/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.2% 8/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.6% 10/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.2% 8/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.9% 9/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Decreased appetite	66.7% 4/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	61.1% 80/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	31.8% 41/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hypoalbuminaemia	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.6% 10/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.9% 5/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hypoproteinaemia	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hypokalaemia	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.9% 9/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.4% 7/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hyponatraemia	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.9% 5/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Abnormal loss of weight	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	4.6% 6/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Dysgeusia	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	11.5% 15/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.9% 5/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Headache	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.9% 9/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.1% 4/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Hypoaesthesia	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	9.9% 13/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.4% 7/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Neuropathy peripheral	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	14.5% 19/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	15.5% 20/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Myoclonus	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Peripheral sensory neuropathy	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	25.2% 33/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	21.7% 28/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Somnolence	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Nervous system disorders Dizziness	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	9.2% 12/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.2% 8/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Alopecia	83.3% 5/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	66.7% 4/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	67.2% 88/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	56.6% 73/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Rash	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	48.9% 64/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	14.7% 19/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Dry skin	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	9.2% 12/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.1% 4/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Nail disorder	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	11.5% 15/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	4.7% 6/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Pruritus	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	17.6% 23/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	8.5% 11/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.6% 10/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Pigmentation disorder	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Skin fissures	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.1% 4/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Cold sweat	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Pyrexia	66.7% 4/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	27.5% 36/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	12.4% 16/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Fatigue	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	66.7% 4/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	42.7% 56/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	37.2% 48/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Chills	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Oedema	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.8% 5/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Thirst	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Influenza like illness	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.9% 5/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Oedema peripheral	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	4.6% 6/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.2% 8/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Asthenia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	15.3% 20/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.2% 8/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
General disorders Malaise	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.1% 8/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.1% 4/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Alanine aminotransferase increased	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	66.7% 4/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	12.2% 16/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	8.5% 11/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Aspartate aminotransferase increased	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	10.7% 14/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	10.9% 14/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood alkaline phosphatase increased	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.6% 10/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.4% 7/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood albumin decreased	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	4.6% 6/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood chloride decreased	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood urine present	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Gamma-glutamyltransferase increased	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood amylase increased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood calcium decreased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood creatinine increased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.8% 5/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood potassium decreased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.3% 7/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood urea increased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Glucose urine present	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Monocyte count decreased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Platelet count increased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Protein urine present	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Specific gravity urine decreased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Weight decreased	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	37.4% 49/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	22.5% 29/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Haemoglobin decreased	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	15.3% 20/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	14.7% 19/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood bilirubin increased	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	4.6% 6/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.4% 7/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Blood chloride increased	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations White blood cell count decreased	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	21.4% 28/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	19.4% 25/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Investigations Neutrophil count decreased	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	17.6% 23/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	14.0% 18/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Hepatobiliary disorders Biliary dilatation	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Hepatobiliary disorders Hepatic function abnormal	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.3% 7/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Hepatobiliary disorders Hyperbilirubinaemia	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.1% 8/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Musculoskeletal and connective tissue disorders Myalgia	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.0% 21/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	17.1% 22/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Musculoskeletal and connective tissue disorders Muscle spasms	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	12.2% 16/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	11.6% 15/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	10.7% 14/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	10.1% 13/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	8.4% 11/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.8% 10/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Respiratory, thoracic and mediastinal disorders Epistaxis	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.8% 22/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	2.3% 3/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Respiratory, thoracic and mediastinal disorders Hiccups	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.9% 9/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.9% 5/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.3% 7/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Infection	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	5.3% 7/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.78% 1/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Nasopharyngitis	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.6% 10/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.0% 9/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Paronychia	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	9.9% 13/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Pneumonia	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.1% 4/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.1% 4/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Bronchitis	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Neutropenic infection	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.6% 10/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.9% 5/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Psychiatric disorders Insomnia	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	50.0% 3/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	7.6% 10/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	6.2% 8/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Renal and urinary disorders Proteinuria	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	3.8% 5/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.6% 2/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Renal and urinary disorders Dysuria	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	1.5% 2/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Renal and urinary disorders Hydronephrosis	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Renal and urinary disorders Urinary retention	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.76% 1/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Cardiac disorders Sinus tachycardia	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Cardiac disorders Supraventricular tachycardia	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Eye disorders Visual acuity reduced	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.
Injury, poisoning and procedural complications Post gastric surgery syndrome	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/131 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.	0.00% 0/129 • Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to 30 days after the last dose (up to 51.7 weeks in the Pilot part and up to 110.3 weeks in the Randomized part). SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.

Additional Information

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