Trial Outcomes & Findings for Efficacy and Safety of Roxadustat for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome With Low Red Blood Cell Transfusion Burden (NCT NCT03263091)

NCT ID: NCT03263091

Last Updated: 2024-08-01

Results Overview

The RBC TI was defined as the absence of any intravenous (IV) RBC transfusion (packed cell or whole blood) during any consecutive 56 days during the treatment period. Data presented is for number of participants with RBC TI ≥8 weeks (≥56 consecutive days) since first dose in the first 28 weeks of treatment.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 184 participants
• Primary outcome timeframe: 28 weeks
• Results posted on: 2024-08-01

Participant Flow

The study included 3 components: Open-label (OL) Lead-in, Double-blind (DB), and OL High-erythropoietin (High-EPO) component.

Participants were enrolled in sequential dose level cohorts in OL lead-in component prior to the start of DB component. Concurrent with enrollment in DB component, participants with high serum EPO levels (>400 milli-international units [mIU]/milliliter [mL]), exclusionary for DB component, were enrolled in an OL high-EPO component. Participants with lower-risk myelodysplastic syndrome (MDS) with low transfusion burden (LTB) were randomized 3:2 to roxadustat or matching placebo in DB component.

Participant milestones

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg Participants received roxadustat 1.5 milligrams (mg)/kilograms (kg), three times a week (TIW) for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Roxadustat Participants received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Placebo Participants received placebo matched to roxadustat for 52 weeks.
OL Component STARTED	8	8	8	0	0	0
OL Component Received at Least 1 Dose of Study Drug	8	8	8	0	0	0
OL Component COMPLETED	6	6	6	0	0	0
OL Component NOT COMPLETED	2	2	2	0	0	0
OL High-EPO Component STARTED	0	0	0	20	0	0
OL High-EPO Component Received at Least 1 Dose of Study Drug	0	0	0	20	0	0
OL High-EPO Component COMPLETED	0	0	0	10	0	0
OL High-EPO Component NOT COMPLETED	0	0	0	10	0	0
DB Component STARTED	0	0	0	0	82	58
DB Component Received at Least 1 Dose of Study Drug	0	0	0	0	82	58
DB Component COMPLETED	0	0	0	0	38	37
DB Component NOT COMPLETED	0	0	0	0	44	21

Reasons for withdrawal

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg Participants received roxadustat 1.5 milligrams (mg)/kilograms (kg), three times a week (TIW) for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Roxadustat Participants received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Placebo Participants received placebo matched to roxadustat for 52 weeks.
OL Component Withdrawal by Subject	1	1	0	0	0	0
OL Component Physician Decision	0	1	2	0	0	0
OL Component Death	1	0	0	0	0	0
OL High-EPO Component Withdrawal by Subject	0	0	0	6	0	0
OL High-EPO Component Physician Decision	0	0	0	1	0	0
OL High-EPO Component Death	0	0	0	3	0	0
DB Component Withdrawal by Subject	0	0	0	0	22	8
DB Component Physician Decision	0	0	0	0	3	1
DB Component Adverse Event	0	0	0	0	2	1
DB Component Lost to Follow-up	0	0	0	0	2	1
DB Component Death	0	0	0	0	7	4
DB Component Other than specified	0	0	0	0	8	6

Baseline Characteristics

Efficacy and Safety of Roxadustat for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome With Low Red Blood Cell Transfusion Burden

Baseline characteristics by cohort

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=8 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=8 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg n=8 Participants Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg n=20 Participants Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Roxadustat n=82 Participants Participants received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Placebo n=58 Participants Participants received placebo matched to roxadustat for 52 weeks.	Total n=184 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	0 Participants n=483 Participants	3 Participants n=36 Participants	1 Participants n=10 Participants	6 Participants n=115 Participants
Age, Customized <65 Years	3 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	8 Participants n=483 Participants	18 Participants n=36 Participants	14 Participants n=10 Participants	45 Participants n=115 Participants
Age, Customized ≥65 Years	5 Participants n=93 Participants	8 Participants n=4 Participants	6 Participants n=27 Participants	12 Participants n=483 Participants	64 Participants n=36 Participants	44 Participants n=10 Participants	139 Participants n=115 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants	6 Participants n=483 Participants	36 Participants n=36 Participants	21 Participants n=10 Participants	75 Participants n=115 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	5 Participants n=4 Participants	2 Participants n=27 Participants	14 Participants n=483 Participants	46 Participants n=36 Participants	37 Participants n=10 Participants	109 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	2 Participants n=10 Participants	6 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=93 Participants	7 Participants n=4 Participants	6 Participants n=27 Participants	19 Participants n=483 Participants	78 Participants n=36 Participants	55 Participants n=10 Participants	172 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants	14 Participants n=36 Participants	7 Participants n=10 Participants	24 Participants n=115 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) White	7 Participants n=93 Participants	8 Participants n=4 Participants	8 Participants n=27 Participants	17 Participants n=483 Participants	63 Participants n=36 Participants	49 Participants n=10 Participants	152 Participants n=115 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	5 Participants n=36 Participants	2 Participants n=10 Participants	8 Participants n=115 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The full analysis set (FAS) included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment hemoglobin (Hb) assessment.

The RBC TI was defined as the absence of any intravenous (IV) RBC transfusion (packed cell or whole blood) during any consecutive 56 days during the treatment period. Data presented is for number of participants with RBC TI ≥8 weeks (≥56 consecutive days) since first dose in the first 28 weeks of treatment.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=8 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=8 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg n=8 Participants Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg n=20 Participants Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
OL and OL High-EPO Components: Number of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) ≥8 Weeks (≥56 Consecutive Days) Since First Dose in the First 28 Weeks of Treatment	3 Participants	1 Participants	5 Participants	3 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment.

RBC TI was defined as the absence of any IV RBC transfusion (packed cell or whole blood) during any consecutive 56 days during the treatment period. Data presented is for number of participants with RBC TI ≥56 consecutive days since first dose in the first 28 weeks of treatment.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=80 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=57 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Number of Participants Who Achieved RBC TI ≥56 Consecutive Days Since First Dose in the First 28 Weeks of Treatment	38 Participants	19 Participants	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 8

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment.

Number of pRBC transfusions at baseline was defined as pRBC transfusions requirement during 8-week period prior to the start of first study medication. Responders were defined as participants with at least a 50% reduction in the number of pRBC transfusions over any 8-week (56 consecutive days) period during the study as compared with the baseline.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=8 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=8 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg n=8 Participants Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg n=20 Participants Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
OL and OL High-EPO Components: Number of Participants Who Achieved TI ≥50% Reduction From Baseline in Number of Packs of Red Blood Cells (pRBC) Transfusions Over 8 Weeks	5 Participants	3 Participants	7 Participants	8 Participants

SECONDARY outcome

Timeframe: 52 weeks

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment.

RBC TI was defined as the absence of any IV RBC transfusion (packed cell or whole blood) during any consecutive 56 days during the treatment period. Data presented is for number of participants with RBC TI ≥56 consecutive days since first dose in the 52 weeks of treatment.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=80 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=57 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Number of Participants Who Achieved TI ≥56 Consecutive Days Since First Dose in 52 Weeks of Treatment	44 Participants	23 Participants	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 56

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment.

RBC TI was defined as the absence of any IV RBC transfusion (packed cell or whole blood) during any consecutive 56 days anytime during the study (up to Week 56).

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=80 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=57 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Number of Participants Who Achieved TI ≥56 Consecutive Days Anytime During the Study	52 Participants	29 Participants	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 8

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment.

Baseline number of transfusions (pRBC/8-weeks) = total number of packs of rRBCs within 16 weeks prior to first dose/2. A pRBC transfusion reduction responder was defined as a participant who achieved ≥50% reduction in number of pRBC transfusions over 8 weeks compared to their baseline for any 8 week period in the duration begining with the first dose date (Day 1) and ending with the end of study or treatment discontinuation due to adverse event (AE)/serious adverse event (SAE) or death, whichever came earlier.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=80 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=57 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Number of Participants Who Achieved ≥50% Reduction From Baseline in Number of pRBC Transfusions Over 8 Weeks	59 Participants	37 Participants	—	—

SECONDARY outcome

Timeframe: 28 weeks

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment.

The PEW of TI periods over the first 28 weeks was added up to a cumulative number of weeks. For a participant with at least 1 TI response period over the first 28 weeks, the last TI response period was ended with the date of a subsequent RBC transfusion, visit date at Week 28, date of the end of study or treatment discontinuation due to AE/SAE or death, whichever came earlier. For a participant with no TI response period over the first 28 weeks, the cumulative number of PEW was set to zero.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=80 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=57 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Cumulative Number of Participant Exposure Weeks (PEW) of TI Over the First 28 Weeks of Treatment	9.60 weeks Standard Deviation 11.537	7.60 weeks Standard Deviation 11.557	—	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment.

Number of pRBC transfusions at baseline was defined as pRBC transfusions requirement during 8-week period prior to the start of first study medication.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=80 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=57 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Change From Baseline in Number of pRBC Packs Transfused Over the First 28 Weeks of Treatment	-0.13 pRBC packs Standard Deviation 2.314	0.44 pRBC packs Standard Deviation 1.833	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 56

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment.

≥20 consecutive weeks TI was defined as the absence of any IV RBC transfusion (packed cell or whole blood) during any consecutive 140 days anytime during the study (up to 56 weeks). TI was estimated between the first dose date (Day 1) and the end of study (Week 56) or treatment discontinuation due to AE/SAE or death, whichever came earlier.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=80 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=57 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Number of Participants Who Achieved TI ≥20 Consecutive Weeks During the Study	23 Participants	15 Participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 9

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The PROMIS physical function item measures self-reported, current capability to carry out activities that require physical actions, ranging from self-care (activities of daily living) to more complex activities that require a combination of skills, often within a social context. The PF 10-item short form which contains 10 questions was used in this study, and each item was scored on a 5-point rating scale (1 [unable to do] to 5 [without any difficulty]), with higher scores indicating better functioning. Total raw score was the sum of the response to each question, with the lowest possible raw score 10 (poor physical function) and the highest possible raw score 50 (better physical function). Raw scores converted to T-scores (as detailed in the T-score conversion table for PROMIS-SF v2.0 Physical Function 10b) with a mean of 50 and a standard deviation (SD) of 10. T-scores ranged from minimum 13.8 to maximum 61.3 possible scores with higher scores indicating better physical functioning.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=71 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=52 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Mean Change From Baseline in the Patient-Reported Outcomes Measurement Information System-Short Form (PROMIS-SF) v2.0 Physical Function (PF) 10b Score at Week 9	-1.9 T-score Standard Deviation 7.29	-0.4 T-score Standard Deviation 6.77	—	—

SECONDARY outcome

Timeframe: Baseline, Week 9

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Fatigue was measured using the 13-item fatigue scale of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System, each item was scored on a 5-point rating scale ranging from 1 "not at all" to 5 "very much", with lower scores indicating better functioning. Total raw score was the sum of the response to each question, with the lowest possible raw score 13 (lowest level of fatigue) and the highest possible raw score 65 (highest level of fatigue), with lower scores indicating better functioning. Raw scores converted to T-scores (as detailed in the T-score conversion table for PROMIS-SF v1.0 Fatigue 13a) with a mean of 50 and a SD of 10. T-scores ranged from minimum 30.3 to maximum 83.5 possible scores with lower scores indicating better functioning.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=67 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=52 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Mean Change From Baseline in the PROMIS-SF v1.0 Fatigue 13a Score at Week 9	1.9 T-score Standard Deviation 7.61	-0.6 T-score Standard Deviation 7.36	—	—

SECONDARY outcome

Timeframe: Baseline, Week 9

Population: FAS included all enrolled participants who received at least 1 dose of study medication, and at least 1 corresponding on-treatment Hb assessment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The EQ-5D questionnaire is designed for self-completion by participants. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problem, moderate problems, severe problems, and unable to/extreme problems. The questionnaire also included a visual analogue scale, where the participant was asked to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state and 100 being the best imaginable health.

Outcome measures

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=71 Participants Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=55 Participants Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.
DB Component: Mean Change From Baseline in the European Quality of Life Five Dimensional Five Level Health Questionnaire (EQ-5D-5L) Visual Analogue Scale Score at Week 9	-1.7 units on a scale Standard Deviation 20.31	1.6 units on a scale Standard Deviation 16.18	—	—

Adverse Events

OL Component (Cohort 1): Roxadustat 1.5 mg/kg

Serious events: 4 serious events

Other events: 7 other events

Deaths: 1 deaths

OL Component (Cohort 2): Roxadustat 2.0 mg/kg

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

OL Component (Cohort 3): Roxadustat 2.5 mg/kg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

OL High-EPO Component: Roxadustat 2.5 mg/kg

Serious events: 6 serious events

Other events: 15 other events

Deaths: 3 deaths

DB Component: Roxadustat

Serious events: 22 serious events

Other events: 68 other events

Deaths: 7 deaths

DB Component: Placebo

Serious events: 10 serious events

Other events: 46 other events

Deaths: 4 deaths

Serious adverse events

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=8 participants at risk Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=8 participants at risk Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg n=8 participants at risk Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg n=20 participants at risk Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Roxadustat n=82 participants at risk Participants received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Placebo n=58 participants at risk Participants received placebo matched to roxadustat for 52 weeks.
Blood and lymphatic system disorders Febrile neutropenia	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Anaemia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Acute myocardial infarction	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Acute left ventricular failure	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac failure	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Supraventricular tachycardia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Colitis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Inguinal hernia	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Multiple organ dysfunction syndrome	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Oedema	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Pyrexia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders General physical health deterioration	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Mucosal inflammation	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Portal hypertension	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	4.9% 4/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations COVID-19	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Appendicitis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Diverticulitis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Pyelonephritis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Septic shock	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Urosepsis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Campylobacter gastroenteritis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Influenza	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Head injury	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Limb injury	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Traumatic haemorrhage	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Transient ischaemic attack	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Brain oedema	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Ischaemic stroke	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Syncope	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Carotid artery stenosis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.2% 3/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Ureteric stenosis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Haematuria	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.

Other adverse events

Measure	OL Component (Cohort 1): Roxadustat 1.5 mg/kg n=8 participants at risk Participants received roxadustat 1.5 mg/kg, TIW for 52 weeks.	OL Component (Cohort 2): Roxadustat 2.0 mg/kg n=8 participants at risk Participants received roxadustat 2.0 mg/kg, TIW for 52 weeks.	OL Component (Cohort 3): Roxadustat 2.5 mg/kg n=8 participants at risk Participants received roxadustat 2.5 mg/kg, TIW for 52 weeks.	OL High-EPO Component: Roxadustat 2.5 mg/kg n=20 participants at risk Participants with high serum EPO levels (\>400 mIU/mL) received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Roxadustat n=82 participants at risk Participants received roxadustat 2.5 mg/kg TIW for 52 weeks.	DB Component: Placebo n=58 participants at risk Participants received placebo matched to roxadustat for 52 weeks.
Blood and lymphatic system disorders Haemorrhagic diathesis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.9% 4/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.1% 5/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Angina pectoris	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.7% 3/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac failure chronic	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Palpitations	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Cardiac disorders Tachycardia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Endocrine disorders Hypothyroidism	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Eye disorders Dry eye	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Eye disorders Visual impairment	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal distension	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.9% 4/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	15.0% 3/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	13.4% 11/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	37.5% 3/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.0% 2/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	7.3% 6/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	15.5% 9/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dry mouth	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	4.9% 4/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Haemorrhoids	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Mouth haemorrhage	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Mouth ulceration	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	23.2% 19/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.1% 7/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	7.3% 6/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Asthenia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	20.0% 4/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	13.4% 11/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.1% 7/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Fatigue	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.0% 2/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	18.3% 15/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.3% 6/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders General physical health deterioration	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Generalised oedema	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Influenza like illness	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Malaise	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Non-cardiac chest pain	37.5% 3/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Oedema peripheral	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.0% 2/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	11.0% 9/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.9% 4/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Pyrexia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.1% 5/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Gallbladder disorder	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Jaundice	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Immune system disorders Seasonal allergy	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Anal abscess	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Atypical pneumonia	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations COVID-19	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	4.9% 4/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.3% 6/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Gingivitis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Kidney infection	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	4.9% 4/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	8.6% 5/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Onychomycosis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Oral candidiasis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Pharyngitis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.2% 3/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Respiratory tract infection	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Sinusitis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Tonsillitis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	8.6% 5/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.0% 2/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Injury	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Nasal injury	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Post-traumatic pain	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Investigations Alanine aminotransferase increased	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.2% 10/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.1% 7/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Investigations Aspartate aminotransferase increased	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	15.0% 3/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	9.8% 8/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.9% 4/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Investigations Blood alkaline phosphatase increased	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Investigations Blood bilirubin increased	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	7.3% 6/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Investigations Blood creatinine increased	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Investigations Lymphocyte count decreased	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Investigations Weight decreased	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.0% 2/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	8.5% 7/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased appetite	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	7.3% 6/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	8.6% 5/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Folate deficiency	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	4.9% 4/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.9% 4/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.0% 2/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.1% 5/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	8.6% 5/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle contracture	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.1% 5/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.7% 3/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.2% 3/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Oligoarthritis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	10.0% 2/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sweat gland tumour	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	13.4% 11/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	17.2% 10/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Headache	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	8.5% 7/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	6.9% 4/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Hypoaesthesia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Neuralgia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Presyncope	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Restless legs syndrome	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Sciatica	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Anxiety	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	2.4% 2/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Depression	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	11.0% 9/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.2% 3/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Chronic kidney disease	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Proteinuria	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal cyst	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	4.9% 4/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	9.8% 8/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.2% 3/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoventilation	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal inflammation	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	5.0% 1/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Lichen planus	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Madarosis	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	9.8% 8/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Trichodynia	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	25.0% 2/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	4.9% 4/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Vascular disorders Orthostatic hypotension	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.2% 1/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.
Vascular disorders Pallor	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	12.5% 1/8 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/20 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/82 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/58 • Baseline up to Week 56 The safety analysis set included all participants who received at least 1 dose of study drug.

Additional Information

Clinical Trial Information Desk

FibroGen, Inc.

Phone: 415-978-1441

Email: 082MDSstudy@fibrogen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The multisite consortium can publish any time after the data is collected and analyzed by FibroGen. The investigator can only publish after the multisite consortium publishes (or tries to publish and fails). FibroGen has 60 days to review a publication and can extend the embargo up to an additional 120 days (or 180 total).
• Publication restrictions are in place

Restriction type: OTHER