Trial Outcomes & Findings for Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL) (NCT NCT02669017)

Last Updated: 2021-05-19

Results Overview

A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as: * CTCAE Grade 3 or 4 febrile neutropenia or neutropenic infection. * CTCAE Grade 4 neutropenia lasting \>7 days. * CTCAE Grade 4 thrombocytopenia. * CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion. * CTCAE Grade 4 anemia. A non-hematologic DLT is defined as: * CTCAE Grade 4 tumor lysis syndrome (TLS). Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage. * CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). * CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). * CTCAE Grade 2 or higher skin ulceration.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

183 participants

Primary outcome timeframe

Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)

Results posted on

2021-05-19

Participant Flow

Participants were screened at 11 sites in 3 countries.

Participant milestones

Participant milestones
Measure	Part 1: 15 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Overall Study STARTED	4	4	4	5	16	26	19	69	36
Overall Study COMPLETED	3	2	2	1	4	7	8	7	11
Overall Study NOT COMPLETED	1	2	2	4	12	19	11	62	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: 15 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Overall Study Death	1	2	2	3	8	18	10	47	20
Overall Study Withdrawal by Subject	0	0	0	1	2	0	0	2	2
Overall Study Lost to Follow-up	0	0	0	0	0	0	0	0	1
Overall Study Miscellaneous	0	0	0	0	2	1	1	13	2

Baseline Characteristics

Height data was not collected for 2 participants because of complications during the collection of baseline measurements.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=16 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=26 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=19 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 150 μg/kg Q3W n=69 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W n=36 Participants Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Total n=183 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	0 Participants n=26 Participants	0 Participants n=19 Participants	0 Participants n=69 Participants	0 Participants n=36 Participants	0 Participants n=183 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=4 Participants	1 Participants n=4 Participants	3 Participants n=4 Participants	2 Participants n=5 Participants	3 Participants n=16 Participants	14 Participants n=26 Participants	13 Participants n=19 Participants	43 Participants n=69 Participants	19 Participants n=36 Participants	99 Participants n=183 Participants
Age, Categorical >=65 years	3 Participants n=4 Participants	3 Participants n=4 Participants	1 Participants n=4 Participants	3 Participants n=5 Participants	13 Participants n=16 Participants	12 Participants n=26 Participants	6 Participants n=19 Participants	26 Participants n=69 Participants	17 Participants n=36 Participants	84 Participants n=183 Participants
Age, Continuous	72.5 years STANDARD_DEVIATION 8.39 • n=4 Participants	68.3 years STANDARD_DEVIATION 11.53 • n=4 Participants	51.3 years STANDARD_DEVIATION 18.82 • n=4 Participants	68.2 years STANDARD_DEVIATION 12.38 • n=5 Participants	71.0 years STANDARD_DEVIATION 10.20 • n=16 Participants	63.7 years STANDARD_DEVIATION 13.37 • n=26 Participants	58.5 years STANDARD_DEVIATION 13.96 • n=19 Participants	58.7 years STANDARD_DEVIATION 15.82 • n=69 Participants	61.7 years STANDARD_DEVIATION 12.82 • n=36 Participants	61.7 years STANDARD_DEVIATION 14.49 • n=183 Participants
Sex: Female, Male Female	2 Participants n=4 Participants	2 Participants n=4 Participants	2 Participants n=4 Participants	3 Participants n=5 Participants	3 Participants n=16 Participants	7 Participants n=26 Participants	6 Participants n=19 Participants	34 Participants n=69 Participants	10 Participants n=36 Participants	69 Participants n=183 Participants
Sex: Female, Male Male	2 Participants n=4 Participants	2 Participants n=4 Participants	2 Participants n=4 Participants	2 Participants n=5 Participants	13 Participants n=16 Participants	19 Participants n=26 Participants	13 Participants n=19 Participants	35 Participants n=69 Participants	26 Participants n=36 Participants	114 Participants n=183 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	1 Participants n=26 Participants	1 Participants n=19 Participants	3 Participants n=69 Participants	1 Participants n=36 Participants	6 Participants n=183 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=4 Participants	4 Participants n=4 Participants	4 Participants n=4 Participants	5 Participants n=5 Participants	16 Participants n=16 Participants	25 Participants n=26 Participants	18 Participants n=19 Participants	65 Participants n=69 Participants	35 Participants n=36 Participants	176 Participants n=183 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	0 Participants n=26 Participants	0 Participants n=19 Participants	1 Participants n=69 Participants	0 Participants n=36 Participants	1 Participants n=183 Participants
Race/Ethnicity, Customized Race · White	4 Participants n=4 Participants	4 Participants n=4 Participants	4 Participants n=4 Participants	4 Participants n=5 Participants	14 Participants n=16 Participants	19 Participants n=26 Participants	19 Participants n=19 Participants	61 Participants n=69 Participants	35 Participants n=36 Participants	164 Participants n=183 Participants
Race/Ethnicity, Customized Race · Black or African American	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	1 Participants n=5 Participants	1 Participants n=16 Participants	4 Participants n=26 Participants	0 Participants n=19 Participants	5 Participants n=69 Participants	0 Participants n=36 Participants	11 Participants n=183 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	1 Participants n=16 Participants	2 Participants n=26 Participants	0 Participants n=19 Participants	0 Participants n=69 Participants	0 Participants n=36 Participants	3 Participants n=183 Participants
Race/Ethnicity, Customized Race · American Indian or Alaskan Native	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	0 Participants n=26 Participants	0 Participants n=19 Participants	0 Participants n=69 Participants	0 Participants n=36 Participants	0 Participants n=183 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Pacific Islander	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	0 Participants n=26 Participants	0 Participants n=19 Participants	0 Participants n=69 Participants	0 Participants n=36 Participants	0 Participants n=183 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	1 Participants n=26 Participants	0 Participants n=19 Participants	1 Participants n=69 Participants	1 Participants n=36 Participants	3 Participants n=183 Participants
Race/Ethnicity, Customized Race · Unknown or Not Reported	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	0 Participants n=26 Participants	0 Participants n=19 Participants	2 Participants n=69 Participants	0 Participants n=36 Participants	2 Participants n=183 Participants
Height	172.23 cm STANDARD_DEVIATION 18.438 • n=4 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	170.73 cm STANDARD_DEVIATION 12.545 • n=4 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	173.65 cm STANDARD_DEVIATION 11.544 • n=4 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	167.68 cm STANDARD_DEVIATION 10.275 • n=5 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	170.72 cm STANDARD_DEVIATION 8.977 • n=16 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	171.47 cm STANDARD_DEVIATION 9.790 • n=26 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	172.79 cm STANDARD_DEVIATION 10.584 • n=19 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	170.56 cm STANDARD_DEVIATION 11.908 • n=68 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	171.29 cm STANDARD_DEVIATION 12.193 • n=35 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.	171.11 cm STANDARD_DEVIATION 11.221 • n=181 Participants • Height data was not collected for 2 participants because of complications during the collection of baseline measurements.
Weight	73.65 kg STANDARD_DEVIATION 7.204 • n=4 Participants	78.73 kg STANDARD_DEVIATION 25.445 • n=4 Participants	79.95 kg STANDARD_DEVIATION 26.942 • n=4 Participants	86.38 kg STANDARD_DEVIATION 23.597 • n=5 Participants	86.89 kg STANDARD_DEVIATION 25.996 • n=16 Participants	78.66 kg STANDARD_DEVIATION 18.113 • n=26 Participants	88.67 kg STANDARD_DEVIATION 20.820 • n=19 Participants	77.87 kg STANDARD_DEVIATION 22.453 • n=69 Participants	88.71 kg STANDARD_DEVIATION 24.834 • n=36 Participants	82.23 kg STANDARD_DEVIATION 22.635 • n=183 Participants
Body Mass Index (BMI)	25.21 kg/m^2 STANDARD_DEVIATION 3.971 • n=4 Participants • BMI could not be calculated for 2 participants due to missing height information.	26.60 kg/m^2 STANDARD_DEVIATION 5.466 • n=4 Participants • BMI could not be calculated for 2 participants due to missing height information.	25.89 kg/m^2 STANDARD_DEVIATION 5.428 • n=4 Participants • BMI could not be calculated for 2 participants due to missing height information.	30.77 kg/m^2 STANDARD_DEVIATION 8.931 • n=5 Participants • BMI could not be calculated for 2 participants due to missing height information.	29.40 kg/m^2 STANDARD_DEVIATION 6.882 • n=16 Participants • BMI could not be calculated for 2 participants due to missing height information.	26.68 kg/m^2 STANDARD_DEVIATION 5.458 • n=26 Participants • BMI could not be calculated for 2 participants due to missing height information.	29.57 kg/m^2 STANDARD_DEVIATION 5.575 • n=19 Participants • BMI could not be calculated for 2 participants due to missing height information.	26.62 kg/m^2 STANDARD_DEVIATION 6.648 • n=68 Participants • BMI could not be calculated for 2 participants due to missing height information.	30.15 kg/m^2 STANDARD_DEVIATION 7.235 • n=35 Participants • BMI could not be calculated for 2 participants due to missing height information.	27.93 kg/m^2 STANDARD_DEVIATION 6.587 • n=181 Participants • BMI could not be calculated for 2 participants due to missing height information.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0: Fully Active	2 Participants n=4 Participants	0 Participants n=4 Participants	2 Participants n=4 Participants	0 Participants n=5 Participants	7 Participants n=16 Participants	7 Participants n=26 Participants	4 Participants n=19 Participants	20 Participants n=69 Participants	12 Participants n=36 Participants	54 Participants n=183 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1: Restricted in Physical Activity; Ambulatory	1 Participants n=4 Participants	3 Participants n=4 Participants	2 Participants n=4 Participants	4 Participants n=5 Participants	8 Participants n=16 Participants	19 Participants n=26 Participants	12 Participants n=19 Participants	36 Participants n=69 Participants	21 Participants n=36 Participants	106 Participants n=183 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2: Ambulatory and Capable of All Self-care	1 Participants n=4 Participants	1 Participants n=4 Participants	0 Participants n=4 Participants	1 Participants n=5 Participants	1 Participants n=16 Participants	0 Participants n=26 Participants	2 Participants n=19 Participants	12 Participants n=69 Participants	3 Participants n=36 Participants	21 Participants n=183 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3: Capable of Only Limited Self-care	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	0 Participants n=26 Participants	1 Participants n=19 Participants	1 Participants n=69 Participants	0 Participants n=36 Participants	2 Participants n=183 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 4: Completely Disabled	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	0 Participants n=26 Participants	0 Participants n=19 Participants	0 Participants n=69 Participants	0 Participants n=36 Participants	0 Participants n=183 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 5: Dead	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants	0 Participants n=16 Participants	0 Participants n=26 Participants	0 Participants n=19 Participants	0 Participants n=69 Participants	0 Participants n=36 Participants	0 Participants n=183 Participants

PRIMARY outcome

Timeframe: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)

Population: All participants in Part 1 who completed at least one cycle of treatment.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=3 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=16 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=16 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=25 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	—	—	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)

Population: All participants in Part 1 who completed at least one cycle of treatment.

The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=73 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Recommended Dose of ADCT-402 for Part 2 Recommended Part 2 Dose 1	—	—	120 μg/kg	—	—	—	—	—	—
Recommended Dose of ADCT-402 for Part 2 Recommended Part 2 Dose 2	—	—	150 μg/kg	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 to End of Study (a maximum of 18 months)

Population: All participants who received at least one dose of study treatment.

An adverse event (AE) is defined as any untoward medical occurrence in a participants enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=69 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W n=36 Participants Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=16 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=26 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=19 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)	68 Participants	36 Participants	4 Participants	3 Participants	4 Participants	5 Participants	16 Participants	26 Participants	19 Participants

PRIMARY outcome

Timeframe: Day 1 to End of Study (a maximum of 18 months)

Population: All participants who received at least one dose of study treatment.

An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A treatment emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=69 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W n=36 Participants Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=16 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=26 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=19 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)	40 Participants	15 Participants	1 Participants	1 Participants	0 Participants	4 Participants	4 Participants	14 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline to End of Study (a maximum of 18 months)

Population: All participants who received at least one dose of study treatment with a valid baseline disease assessment and at least one valid post-baseline disease assessment.

ORR was defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) at the time each participant discontinued treatment with ADCT-402, before the start of subsequent anticancer therapy or procedure. Tumor response was assessed using the 2014 Lugano Classification for response. CR is defined as achieving either of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no nonmeasured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR is defined as achieving either of the following: * Partial metabolic response (findings indicate residual disease). * Partial remission (\>50% decrease in target measurable nodes, regression/ absence/ no increase of nonmeasured lesions, spleen regressed by \>50% in length and no new lesions).

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=68 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W n=34 Participants Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=16 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=26 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=19 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Overall Response Rate (ORR)	25 Participants	20 Participants	1 Participants	1 Participants	1 Participants	2 Participants	9 Participants	11 Participants	12 Participants

SECONDARY outcome

Timeframe: Baseline to End of Study (a maximum of 18 months)

Population: All participants who received at least one dose of study treatment with a valid baseline disease assessment and at least one valid post-baseline disease assessment. Results are pooled for all arms as specified in the protocol.

DoR is defined among responders (complete response \[CR\] and partial response \[PR\]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response. Disease progression is defined as progressive metabolic disease or one of the follow: * Target node progression. * An individual extranodal lesion must be abnormal with length \>1.5cm and/or increase of length \>50%. * New or clear progression of nonmeasured lesions. * Regrowth of previously resolved lesions or new nodes \>1.5 cm in length. * New or recurrent bone marrow involvement. DoR is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=180 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Duration of Response (DoR)	—	—	5.36 months Interval 4.04 to Upper limit of the confidence interval was not reached.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to End of Study (a maximum of 18 months)

OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause. OS is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=180 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Overall Survival (OS)	—	—	8.25 months Interval 6.74 to 10.68	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to End of Study (a maximum of 18 months)

PFS is defined among the efficacy population as the time from first dose of study drug until either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response. Disease progression is defined as progressive metabolic disease or one of the follow: * Target node progression. * An individual extranodal lesion must be abnormal with length \>1.5cm and/or increase of length \>50%. * New or clear progression of nonmeasured lesions. * Regrowth of previously resolved lesions or new nodes \>1.5 cm in length. * New or recurrent bone marrow involvement. PFS is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=180 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Progression-free Survival (PFS)	—	—	3.09 months Interval 2.66 to 4.24	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Population: Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=22 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=42 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=88 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=14 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Maximum Observed Serum Concentration (Cmax) for ADCT-402 PBD conjugated Ab: Cycle 1	3798 ng/mL Standard Deviation 1332	—	260 ng/mL Standard Deviation 85.5	404 ng/mL Standard Deviation 161	721 ng/mL Standard Deviation 481	1088 ng/mL Standard Deviation 748	2374 ng/mL Standard Deviation 1040	3416 ng/mL Standard Deviation 3093	3619 ng/mL Standard Deviation 688
Maximum Observed Serum Concentration (Cmax) for ADCT-402 total Ab: Cycle 1	4543 ng/mL Standard Deviation 1805	—	298 ng/mL Standard Deviation 83.7	542 ng/mL Standard Deviation 192	856 ng/mL Standard Deviation 475	1560 ng/mL Standard Deviation 1102	2829 ng/mL Standard Deviation 1257	4383 ng/mL Standard Deviation 4460	4185 ng/mL Standard Deviation 1308
Maximum Observed Serum Concentration (Cmax) for ADCT-402 PBD conjugated Ab: Cycle 2	3178 ng/mL Standard Deviation 1733	—	398 ng/mL Standard Deviation 284	1971 ng/mL Standard Deviation 2566	864 ng/mL Standard Deviation 686	1416 ng/mL Standard Deviation 799	2573 ng/mL Standard Deviation 655	3776 ng/mL Standard Deviation 2738	4293 ng/mL Standard Deviation 1021
Maximum Observed Serum Concentration (Cmax) for ADCT-402 total Ab: Cycle 2	3834 ng/mL Standard Deviation 1913	—	447 ng/mL Standard Deviation 283	2906 ng/mL Standard Deviation 4034	1275 ng/mL Standard Deviation 1025	2422 ng/mL Standard Deviation 983	3142 ng/mL Standard Deviation 888	4798 ng/mL Standard Deviation 3334	5059 ng/mL Standard Deviation 1027
Maximum Observed Serum Concentration (Cmax) for ADCT-402 SG3199: Cycle 1	0.0468 ng/mL Standard Deviation 0.0333	—	—	—	—	0.102 ng/mL Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	0.0372 ng/mL Standard Deviation 0.0208	0.0570 ng/mL Standard Deviation 0.0454	0.0479 ng/mL Standard Deviation 0.0381
Maximum Observed Serum Concentration (Cmax) for ADCT-402 SG3199: Cycle 2	0.0516 ng/mL Standard Deviation 0.0325	—	—	—	—	0.0704 ng/mL Standard Deviation 0.0152	0.0403 ng/mL Standard Deviation 0.0116	0.0485 ng/mL Standard Deviation 0.0449	0.0293 ng/mL Standard Deviation 0.00329

SECONDARY outcome

Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=22 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=42 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=88 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=14 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 total Ab: Cycle 1	0.0837 days Interval 0.0417 to 0.271	—	0.0844 days Interval 0.0438 to 0.292	0.0833 days Interval 0.0431 to 0.0896	0.0833 days Interval 0.0806 to 0.0847	0.0500 days Interval 0.0417 to 0.169	0.0833 days Interval 0.0403 to 0.294	0.0837 days Interval 0.0403 to 0.299	0.0840 days Interval 0.0417 to 0.285
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 SG3199: Cycle 1	0.165 days Interval 0.0417 to 6.81	—	—	—	—	0.0833 days Interval 0.0833 to 0.0833	0.0854 days Interval 0.0458 to 0.172	0.0844 days Interval 0.0417 to 0.294	0.128 days Interval 0.0833 to 0.285
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 PBD conjugated Ab: Cycle 1	0.0840 days Interval 0.0417 to 0.276	—	0.0837 days Interval 0.0833 to 0.0854	0.0833 days Interval 0.0431 to 0.319	0.0819 days Interval 0.0417 to 0.0847	0.0500 days Interval 0.0417 to 0.0875	0.0833 days Interval 0.0403 to 0.296	0.0840 days Interval 0.0417 to 0.305	0.0858 days Interval 0.0417 to 0.285
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 PBD conjugated Ab: Cycle 2	0.0826 days Interval 0.0257 to 0.172	—	0.122 days Interval 0.066 to 0.17	0.0618 days Interval 0.0417 to 0.0875	0.0417 days Interval 0.0222 to 0.165	0.0833 days Interval 0.0229 to 0.0882	0.0830 days Interval 0.0208 to 0.278	0.0642 days Interval 0.0208 to 1.0	0.0854 days Interval 0.0208 to 1.0
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 total Ab: Cycle 2	0.0858 days Interval 0.0257 to 0.172	—	0.0649 days Interval 0.0431 to 0.0868	0.0618 days Interval 0.0417 to 0.0875	0.0417 days Interval 0.0222 to 0.0854	0.0833 days Interval 0.0229 to 0.159	0.0632 days Interval 0.0208 to 0.275	0.0639 days Interval 0.0 to 2.11	0.132 days Interval 0.0208 to 4.0
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 SG3199: Cycle 2	0.162 days Interval 0.0833 to 0.28	—	—	—	—	1.05 days Interval 0.0417 to 2.06	0.120 days Interval 0.084 to 0.153	0.0632 days Interval 0.0222 to 13.8	0.165 days Interval 0.0299 to 0.992

SECONDARY outcome

AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=22 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=42 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=88 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=14 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 PBD conjugated Ab: Cycle 1	30386 day*ng/mL Standard Deviation 16960	—	1063 day*ng/mL Standard Deviation 1340	2390 day*ng/mL Standard Deviation 826	3875 day*ng/mL Standard Deviation 3228	6587 day*ng/mL Standard Deviation 6842	13544 day*ng/mL Standard Deviation 7503	14258 day*ng/mL Standard Deviation 8248	30571 day*ng/mL Standard Deviation 12425
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 PBD conjugated Ab: Cycle 2	39609 day*ng/mL Standard Deviation 24852	—	1933 day*ng/mL Standard Deviation 2289	2955 day*ng/mL Standard Deviation 1132	5573 day*ng/mL Standard Deviation 4827	10369 day*ng/mL Standard Deviation 11656	18707 day*ng/mL Standard Deviation 10505	23109 day*ng/mL Standard Deviation 15370	48183 day*ng/mL Standard Deviation 20288
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 total Ab: Cycle 1	36099 day*ng/mL Standard Deviation 20829	—	1185 day*ng/mL Standard Deviation 1540	3194 day*ng/mL Standard Deviation 1136	5032 day*ng/mL Standard Deviation 4334	8869 day*ng/mL Standard Deviation 9108	15980 day*ng/mL Standard Deviation 7649	16973 day*ng/mL Standard Deviation 9745	33834 day*ng/mL Standard Deviation 14888
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 total Ab: Cycle 2	49892 day*ng/mL Standard Deviation 31012	—	1924 day*ng/mL Standard Deviation 2576	3986 day*ng/mL Standard Deviation 1725	7958 day*ng/mL Standard Deviation 6882	14025 day*ng/mL Standard Deviation 15704	23428 day*ng/mL Standard Deviation 13513	28657 day*ng/mL Standard Deviation 19457	57450 day*ng/mL Standard Deviation 26899
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 SG3199: Cycle 1	0.0436 day*ng/mL Standard Deviation 0.0959	—	—	—	—	0.00213 day*ng/mL Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	0.00462 day*ng/mL Standard Deviation 0.00671	0.0222 day*ng/mL Standard Deviation 0.0423	0.0174 day*ng/mL Standard Deviation 0.0303
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 SG3199: Cycle 2	0.00332 day*ng/mL Standard Deviation 0.00215	—	—	—	—	0.0242 day*ng/mL Standard Deviation 0.0234	0.154 day*ng/mL Standard Deviation 0.286	0.0108 day*ng/mL Standard Deviation 0.0248	0.00425 day*ng/mL Standard Deviation 0.00461

SECONDARY outcome

AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=12 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=3 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=40 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=72 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=11 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 total Ab: Cycle 2	48524 day*ng/mL Standard Deviation 28858	—	2636 day*ng/mL Standard Deviation 3387	4662 day*ng/mL Standard Deviation 2096	10211 day*ng/mL Standard Deviation 8827	17141 day*ng/mL Standard Deviation 15029	24247 day*ng/mL Standard Deviation 10902	28041 day*ng/mL Standard Deviation 15312	46469 day*ng/mL Standard Deviation 12675
Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 PBD conjugated Ab: Cycle 2	38466 day*ng/mL Standard Deviation 23514	—	2285 day*ng/mL Standard Deviation 2928	3458 day*ng/mL Standard Deviation 1426	10575 day*ng/mL Standard Deviation 1121	10171 day*ng/mL Standard Deviation 11244	19890 day*ng/mL Standard Deviation 8968	22859 day*ng/mL Standard Deviation 12080	39362 day*ng/mL Standard Deviation 9800

SECONDARY outcome

AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=13 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=3 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=2 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=2 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=2 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=15 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=47 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 total Ab: Cycle 1	43952 day*ng/mL Standard Deviation 24032	—	869 day*ng/mL Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	—	—	16409 day*ng/mL Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	13292 day*ng/mL Standard Deviation 8495	12692 day*ng/mL Standard Deviation 8968	38991 day*ng/mL Standard Deviation 53597
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 SG3199: Cycle 1	—	—	—	—	—	—	—	0.154 day*ng/mL Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	—
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 PBD conjugated Ab: Cycle 1	32629 day*ng/mL Standard Deviation 19488	—	432 day*ng/mL Standard Deviation 173	2001 day*ng/mL Standard Deviation 663	5333 day*ng/mL Standard Deviation 4002	5622 day*ng/mL Standard Deviation 7170	10232 day*ng/mL Standard Deviation 6220	11498 day*ng/mL Standard Deviation 8175	29174 day*ng/mL Standard Deviation 25838

SECONDARY outcome

Thalf of Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=13 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=2 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=38 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=69 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=11 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Terminal Half-life (Thalf) of ADCT-402 PBD conjugated Ab: Cycle 1	10.4 days Interval 0.056 to 19.6	—	1.15 days Interval 1.04 to 2.56	6.84 days Interval 5.74 to 7.94	6.30 days Interval 4.3 to 8.3	3.97 days Interval 0.923 to 7.01	6.33 days Interval 0.515 to 9.5	6.43 days Interval 0.146 to 13.1	7.96 days Interval 6.43 to 16.6
Terminal Half-life (Thalf) of ADCT-402 PBD conjugated Ab: Cycle 2	15.5 days Interval 4.82 to 25.0	—	3.98 days Interval 0.909 to 11.1	10.1 days Interval 6.72 to 17.1	16.3 days Interval 11.1 to 21.4	11.4 days Interval 1.78 to 19.2	12.5 days Interval 1.74 to 28.7	11.6 days Interval 1.5 to 33.0	16.3 days Interval 8.14 to 28.8
Terminal Half-life (Thalf) of ADCT-402 total Ab: Cycle 1	12.7 days Interval 0.248 to 19.0	—	2.75 days Interval 2.75 to 2.75	—	—	8.82 days Interval 8.82 to 8.82	7.00 days Interval 0.325 to 10.6	6.58 days Interval 0.0759 to 17.7	9.39 days Interval 0.661 to 18.1
Terminal Half-life (Thalf) of ADCT-402 total Ab: Cycle 2	18.4 days Interval 6.18 to 39.9	—	3.71 days Interval 0.86 to 13.0	9.58 days Interval 7.11 to 15.4	16.5 days Interval 12.9 to 20.0	13.4 days Interval 1.27 to 38.5	14.9 days Interval 2.07 to 33.5	14.3 days Interval 0.269 to 36.0	14.7 days Interval 8.47 to 27.8

SECONDARY outcome

CL of Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=13 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=3 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=40 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=72 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=11 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Apparent Clearance (CL) at Steady State for ADCT-402 PBD conjugated Ab: Cycle 1	12.6 liters/day Standard Deviation 39.4	—	2.49 liters/day Standard Deviation 0.978	1.08 liters/day Standard Deviation 0.164	0.696 liters/day Standard Deviation 0.444	7.13 liters/day Standard Deviation 8.91	2.09 liters/day Standard Deviation 4.07	3.84 liters/day Standard Deviation 8.53	3.11 liters/day Standard Deviation 5.30
Apparent Clearance (CL) at Steady State for ADCT-402 total Ab: Cycle 1	2.02 liters/day Standard Deviation 5.11	—	1.28 liters/day Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	—	—	0.640 liters/day Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	2.47 liters/day Standard Deviation 5.00	3.87 liters/day Standard Deviation 8.95	7.12 liters/day Standard Deviation 9.62
Apparent Clearance (CL) at Steady State for ADCT-402 PBD conjugated Ab: Cycle 2	0.349 liters/day Standard Deviation 0.210	—	1.78 liters/day Standard Deviation 1.80	0.646 liters/day Standard Deviation 0.348	0.415 liters/day Standard Deviation 0.205	19.6 liters/day Standard Deviation 40.6	17.8 liters/day Standard Deviation 109	0.986 liters/day Standard Deviation 2.48	0.407 liters/day Standard Deviation 0.143
Apparent Clearance (CL) at Steady State for ADCT-402 total Ab: Cycle 2	0.323 liters/day Standard Deviation 0.187	—	1.76 liters/day Standard Deviation 1.71	0.577 liters/day Standard Deviation 0.309	38.1 liters/day Standard Deviation 65.5	1.42 liters/day Standard Deviation 2.06	0.581 liters/day Standard Deviation 0.660	1.05 liters/day Standard Deviation 2.91	0.417 liters/day Standard Deviation 0.161
Apparent Clearance (CL) at Steady State for ADCT-402 SG3199: Cycle 1	—	—	—	—	—	—	—	627 liters/day Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	—

SECONDARY outcome

Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=13 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=2 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=38 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=69 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=11 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Volume of Distribution at Steady State (Vss) for ADCT-402 PBD conjugated Ab: Cycle 1	7.18 liters Standard Deviation 2.52	—	4.47 liters Standard Deviation 0.759	10.3 liters Standard Deviation 4.83	4.96 liters Standard Deviation 0.318	9.68 liters Standard Deviation 2.68	5.95 liters Standard Deviation 1.86	7.59 liters Standard Deviation 6.18	11.5 liters Standard Deviation 11.1
Volume of Distribution at Steady State (Vss) for ADCT-402 total Ab: Cycle 1	7.20 liters Standard Deviation 2.03	—	4.71 liters Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	—	—	7.84 liters Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	5.51 liters Standard Deviation 1.29	6.60 liters Standard Deviation 3.16	7.91 liters Standard Deviation 0.0252
Volume of Distribution at Steady State (Vss) for ADCT-402 PBD conjugated Ab: Cycle 2	6.21 liters Standard Deviation 1.70	—	3.82 liters Standard Deviation 1.25	10.1 liters Standard Deviation 8.57	8.29 liters Standard Deviation 0.540	7.62 liters Standard Deviation 1.09	6.71 liters Standard Deviation 3.13	7.48 liters Standard Deviation 4.29	9.18 liters Standard Deviation 3.43
Volume of Distribution at Steady State (Vss) for ADCT-402 total Ab: Cycle 2	6.86 liters Standard Deviation 2.27	—	3.83 liters Standard Deviation 0.854	9.62 liters Standard Deviation 8.54	7.30 liters Standard Deviation 1.38	8.52 liters Standard Deviation 1.34	8.11 liters Standard Deviation 4.57	8.21 liters Standard Deviation 3.64	9.46 liters Standard Deviation 5.26
Volume of Distribution at Steady State (Vss) for ADCT-402 SG3199: Cycle 1	—	—	—	—	—	—	—	335 liters Standard Deviation NA Standard deviation could not be determined as only one participant had evaluable data.	—

SECONDARY outcome

AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1 (Q3W schedule: 3 week cycle length; Q6W schedule: 6 week cycle length). It is the increase in drug plasma concentration after multiple dosing until a steady state is reached. Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W n=12 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=2 Participants Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=4 Participants Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=38 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=69 Participants Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=11 Participants Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Accumulation Index (AI) for ADCT-402 total Ab: Cycle 2	1.36 ratio Standard Deviation 0.314	—	1.15 ratio Standard Deviation 0.229	1.35 ratio Standard Deviation 0.252	1.71 ratio Standard Deviation 0.325	1.80 ratio Standard Deviation 0.962	1.62 ratio Standard Deviation 0.492	1.63 ratio Standard Deviation 0.486	1.78 ratio Standard Deviation 0.418
Accumulation Index (AI) for ADCT-402 PBD conjugated Ab: Cycle 2	1.23 ratio Standard Deviation 0.160	—	1.12 ratio Standard Deviation 0.173	1.37 ratio Standard Deviation 0.264	1.70 ratio Standard Deviation 0.467	1.42 ratio Standard Deviation 0.399	1.47 ratio Standard Deviation 0.369	1.46 ratio Standard Deviation 0.368	1.76 ratio Standard Deviation 0.385

SECONDARY outcome

Timeframe: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)

Population: All participants who were tested for ADA.

Blood serum samples were collected and analysed to determine the presence or absence of ADA. ADA is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.

Outcome measures

Outcome measures
Measure	Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Part 1: 15 μg/kg Q3W n=183 Participants Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).
Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 Confirmed positive ADA pre-dose	—	—	5 Participants	—	—	—	—	—	—
Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 Confirmed positive ADA post-dose only	—	—	1 Participants	—	—	—	—	—	—
Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 Confirmed positive ADA at anytime	—	—	6 Participants	—	—	—	—	—	—

Adverse Events

Part 1: 15 μg/kg Q3W

Serious events: 1 serious events

Other events: 4 other events

Deaths: 1 deaths

Part 1: 30 μg/kg Q3W

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

Part 1: 60 μg/kg Q3W

Serious events: 0 serious events

Other events: 4 other events

Deaths: 2 deaths

Part 1: 90 μg/kg Q3W

Serious events: 4 serious events

Other events: 5 other events

Deaths: 3 deaths

Part 1: 120 μg/kg Q3W

Serious events: 4 serious events

Other events: 16 other events

Deaths: 8 deaths

Part 2: 120 μg/kg Q3W

Serious events: 4 serious events

Other events: 25 other events

Deaths: 18 deaths

Part 1: 150 μg/kg Q3W

Serious events: 6 serious events

Other events: 19 other events

Deaths: 10 deaths

Part 2: 150 μg/kg Q3W

Serious events: 40 serious events

Other events: 65 other events

Deaths: 47 deaths

Part 1: 200 μg/kg Q3W and Q6W

Serious events: 15 serious events

Other events: 36 other events

Deaths: 20 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: 15 μg/kg Q3W n=4 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=16 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=26 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=19 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 150 μg/kg Q3W n=69 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W n=36 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Nausea	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Abdominal compartment syndrome	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Abdominal distension	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Cardiac disorders Pericardial effusion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Cardiac disorders Cardiac arrest	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Cardiac disorders Supraventricular tachycardia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Endocrine disorders Hypothyroidism	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Anal fissure	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Constipation	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Intestinal obstruction	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Intestinal perforation	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Melaena	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Disease progression	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	11.6% 8/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Pyrexia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders General physical health deterioration	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Fatigue	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Generalised oedema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Gait disturbance	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Injection site extravasation	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Non-cardiac chest pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Oedema peripheral	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Hepatobiliary disorders Hepatic failure	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Sepsis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Lung infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Cellulitis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Pneumonia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Clostridium difficile colitis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Clostridium difficile infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Cytomegalovirus infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Enterocolitis infectious	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Influenza	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Lower respiratory tract infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Oesophageal candidiasis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Oropharyngeal candidiasis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Parainfluenzae virus infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Pneumonia haemophilus	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Pneumonia influenzal	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Pneumonia staphylococcal	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Progressive multifocal leukoencephalopathy	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Rhinovirus infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Septic shock	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Staphylococcal sepsis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Injury, poisoning and procedural complications Procedural pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Injury, poisoning and procedural complications Wound	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Alanine aminotransferase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Aspartate aminotransferase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Gamma-glutamyltransferase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Platelet count decreased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Fluid overload	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Failure to thrive	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Muscular weakness	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Neck mass	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Burkitt's lymphoma	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mantle cell lymphoma	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Aphasia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Depressed level of consciousness	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Headache	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Paraesthesia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Syncope	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Psychiatric disorders Confusional state	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Psychiatric disorders Disorientation	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Psychiatric disorders Mental status changes	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Renal and urinary disorders Acute kidney injury	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Renal and urinary disorders Haematuria	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Renal and urinary disorders Urinary retention	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Reproductive system and breast disorders Oedema genital	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Reproductive system and breast disorders Perineal pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Reproductive system and breast disorders Scrotal pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Vascular disorders Embolism	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Vascular disorders Lymphoedema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)

Other adverse events

Other adverse events
Measure	Part 1: 15 μg/kg Q3W n=4 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 30 μg/kg Q3W n=4 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 60 μg/kg Q3W n=4 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 90 μg/kg Q3W n=5 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 120 μg/kg Q3W n=16 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 120 μg/kg Q3W n=26 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 150 μg/kg Q3W n=19 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 2: 150 μg/kg Q3W n=69 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Part 1: 200 μg/kg Q3W and Q6W n=36 participants at risk Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	60.0% 3/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	34.6% 9/26 • Day 1 to End of Study (a maximum of 18 months)	36.8% 7/19 • Day 1 to End of Study (a maximum of 18 months)	36.2% 25/69 • Day 1 to End of Study (a maximum of 18 months)	38.9% 14/36 • Day 1 to End of Study (a maximum of 18 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	40.0% 2/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	24.6% 17/69 • Day 1 to End of Study (a maximum of 18 months)	27.8% 10/36 • Day 1 to End of Study (a maximum of 18 months)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	23.1% 6/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	18.8% 13/69 • Day 1 to End of Study (a maximum of 18 months)	25.0% 9/36 • Day 1 to End of Study (a maximum of 18 months)
Blood and lymphatic system disorders Lymphopenia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Blood and lymphatic system disorders Leukopenia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Cardiac disorders Pericardial effusion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Cardiac disorders Atrial fibrillation	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Eye disorders Periorbital oedema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Eye disorders Dry eye	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Eye disorders Visual impairment	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Nausea	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	25.0% 4/16 • Day 1 to End of Study (a maximum of 18 months)	30.8% 8/26 • Day 1 to End of Study (a maximum of 18 months)	26.3% 5/19 • Day 1 to End of Study (a maximum of 18 months)	31.9% 22/69 • Day 1 to End of Study (a maximum of 18 months)	44.4% 16/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Constipation	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	40.0% 2/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	34.6% 9/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	26.1% 18/69 • Day 1 to End of Study (a maximum of 18 months)	16.7% 6/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Vomiting	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	19.2% 5/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	21.7% 15/69 • Day 1 to End of Study (a maximum of 18 months)	19.4% 7/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	18.8% 13/69 • Day 1 to End of Study (a maximum of 18 months)	13.9% 5/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Abdominal pain	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	23.1% 6/26 • Day 1 to End of Study (a maximum of 18 months)	21.1% 4/19 • Day 1 to End of Study (a maximum of 18 months)	10.1% 7/69 • Day 1 to End of Study (a maximum of 18 months)	19.4% 7/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Abdominal distension	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Dry mouth	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Anal incontinence	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Gastrointestinal disorders Salivary hypersecretion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Fatigue	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	50.0% 2/4 • Day 1 to End of Study (a maximum of 18 months)	60.0% 3/5 • Day 1 to End of Study (a maximum of 18 months)	68.8% 11/16 • Day 1 to End of Study (a maximum of 18 months)	42.3% 11/26 • Day 1 to End of Study (a maximum of 18 months)	42.1% 8/19 • Day 1 to End of Study (a maximum of 18 months)	34.8% 24/69 • Day 1 to End of Study (a maximum of 18 months)	44.4% 16/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Oedema peripheral	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	50.0% 8/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	47.4% 9/19 • Day 1 to End of Study (a maximum of 18 months)	31.9% 22/69 • Day 1 to End of Study (a maximum of 18 months)	38.9% 14/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Pyrexia	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	23.1% 6/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	11.6% 8/69 • Day 1 to End of Study (a maximum of 18 months)	30.6% 11/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Asthenia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Face oedema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Non-cardiac chest pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Chills	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Localised oedema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Malaise	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
General disorders Axillary pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Immune system disorders Food allergy	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Urinary tract infection	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	10.1% 7/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Cellulitis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Rhinitis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Pneumonia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Clostridium difficile infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Oral candidiasis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Respiratory tract infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Clostridium difficile colitis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Influenza	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Sinusitis	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Corona virus infection	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Infections and infestations Pyelonephritis acute	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Injury, poisoning and procedural complications Fall	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	21.1% 4/19 • Day 1 to End of Study (a maximum of 18 months)	10.1% 7/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Injury, poisoning and procedural complications Contusion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Gamma-glutamyltransferase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	80.0% 4/5 • Day 1 to End of Study (a maximum of 18 months)	25.0% 4/16 • Day 1 to End of Study (a maximum of 18 months)	34.6% 9/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	27.5% 19/69 • Day 1 to End of Study (a maximum of 18 months)	47.2% 17/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Blood alkaline phosphatase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	60.0% 3/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	19.2% 5/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	23.2% 16/69 • Day 1 to End of Study (a maximum of 18 months)	25.0% 9/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Aspartate aminotransferase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	40.0% 2/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	20.3% 14/69 • Day 1 to End of Study (a maximum of 18 months)	30.6% 11/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Platelet count decreased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	26.9% 7/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	15.9% 11/69 • Day 1 to End of Study (a maximum of 18 months)	30.6% 11/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Alanine aminotransferase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	40.0% 2/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	19.2% 5/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	15.9% 11/69 • Day 1 to End of Study (a maximum of 18 months)	25.0% 9/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Neutrophil count decreased	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	26.3% 5/19 • Day 1 to End of Study (a maximum of 18 months)	11.6% 8/69 • Day 1 to End of Study (a maximum of 18 months)	22.2% 8/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations White blood cell count decreased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	19.2% 5/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	25.0% 9/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Lymphocyte count decreased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	8.7% 6/69 • Day 1 to End of Study (a maximum of 18 months)	16.7% 6/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Blood creatinine increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Weight decreased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Blood bilirubin increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Amylase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Blood cholesterol increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Lipase increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations International normalised ratio increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Investigations Blood bicarbonate increased	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	23.1% 6/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	15.9% 11/69 • Day 1 to End of Study (a maximum of 18 months)	33.3% 12/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	17.4% 12/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	10.1% 7/69 • Day 1 to End of Study (a maximum of 18 months)	13.9% 5/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	11.6% 8/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Dehydration	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	16.7% 6/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Metabolism and nutrition disorders Gout	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	25.0% 9/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Back pain	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	10.1% 7/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Muscular weakness	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Arthralgia	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Limb mass	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Musculoskeletal and connective tissue disorders Muscle twitching	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Dizziness	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	19.2% 5/26 • Day 1 to End of Study (a maximum of 18 months)	21.1% 4/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Headache	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	13.9% 5/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Dysgeusia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Neuropathy peripheral	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Psychiatric disorders Insomnia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Psychiatric disorders Anxiety	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Reproductive system and breast disorders Breast oedema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	25.0% 4/16 • Day 1 to End of Study (a maximum of 18 months)	26.9% 7/26 • Day 1 to End of Study (a maximum of 18 months)	21.1% 4/19 • Day 1 to End of Study (a maximum of 18 months)	21.7% 15/69 • Day 1 to End of Study (a maximum of 18 months)	19.4% 7/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	40.0% 2/5 • Day 1 to End of Study (a maximum of 18 months)	25.0% 4/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	15.8% 3/19 • Day 1 to End of Study (a maximum of 18 months)	21.7% 15/69 • Day 1 to End of Study (a maximum of 18 months)	22.2% 8/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	26.9% 7/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	20.3% 14/69 • Day 1 to End of Study (a maximum of 18 months)	22.2% 8/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Rash	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	15.4% 4/26 • Day 1 to End of Study (a maximum of 18 months)	42.1% 8/19 • Day 1 to End of Study (a maximum of 18 months)	27.5% 19/69 • Day 1 to End of Study (a maximum of 18 months)	25.0% 9/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	13.0% 9/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Pruritus	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	19.4% 7/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Rash maculo-papular	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	50.0% 2/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	7.2% 5/69 • Day 1 to End of Study (a maximum of 18 months)	13.9% 5/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Skin hyperpigmentation	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	18.8% 3/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Dry skin	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Dermatitis bullous	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	10.5% 2/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	8.3% 3/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	7.7% 2/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	2.9% 2/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	5.6% 2/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	2.8% 1/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	3.8% 1/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	1.4% 1/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Dermatitis acneiform	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	20.0% 1/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Vascular disorders Hypertension	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	12.5% 2/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	5.8% 4/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Vascular disorders Hypotension	50.0% 2/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	6.2% 1/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	11.1% 4/36 • Day 1 to End of Study (a maximum of 18 months)
Vascular disorders Flushing	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	11.5% 3/26 • Day 1 to End of Study (a maximum of 18 months)	5.3% 1/19 • Day 1 to End of Study (a maximum of 18 months)	4.3% 3/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Renal and urinary disorders Bladder spasm	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)
Renal and urinary disorders Urinary retention	25.0% 1/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/4 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/5 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/16 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/26 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/19 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/69 • Day 1 to End of Study (a maximum of 18 months)	0.00% 0/36 • Day 1 to End of Study (a maximum of 18 months)

Additional Information

ADC Therapeutics

Phone: 954-903-7994

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI can publish after first multi-site publication, or if no multi-site publication is made within 18 months of study completion/termination. The only disclosure restriction on the PI is the sponsor can review results comms. prior to public release and can embargo comms. regarding trial results for a period that is more than 60 but less than or equal to 180 days from the time submitted to sponsor for review. The sponsor can't require changes to the communication and can't extend the embargo.
Publication restrictions are in place

Restriction type: OTHER