Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of Daprodustat Compared to Darbepoetin Alfa in Japanese Hemodialysis (HD)-Dependent Subjects With Anemia Associated With Chronic Kidney Disease (CKD) (NCT NCT02969655)

NCT ID: NCT02969655

Last Updated: 2020-11-27

Results Overview

The mean hemoglobin during the Evaluation Period was estimated by a statistical model.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

271 participants

Primary outcome timeframe

Weeks 40 to 52

Results posted on

2020-11-27

Participant Flow

A total of 50 centers, contracted in Japan, enrolled and randomized participants. A total of 271 participants were enrolled and randomized in this study.

A total of 332 participants were screened of which 61 failed screening reasons being participants did not meet inclusion/exclusion criteria (48), physician decision (3) and withdrawn by participant (10), hence 271 participants were enrolled and randomized.

Participant milestones

Participant milestones
Measure	Daprodustat Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Study STARTED	136	135
Overall Study COMPLETED	115	120
Overall Study NOT COMPLETED	21	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Daprodustat Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Study Withdrawal by Subject	3	2
Overall Study Physician Decision	4	3
Overall Study Protocol-specified withdrawal criteria	4	2
Overall Study Adverse Event	10	8

Baseline Characteristics

A Study to Evaluate Efficacy and Safety of Daprodustat Compared to Darbepoetin Alfa in Japanese Hemodialysis (HD)-Dependent Subjects With Anemia Associated With Chronic Kidney Disease (CKD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daprodustat n=136 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=135 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.	Total n=271 Participants Total of all reporting groups
Age, Continuous	64.1 Years STANDARD_DEVIATION 10.30 • n=5 Participants	63.5 Years STANDARD_DEVIATION 10.54 • n=7 Participants	63.8 Years STANDARD_DEVIATION 10.40 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	46 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	91 Participants n=5 Participants	89 Participants n=7 Participants	180 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese heritage	136 Count of participants n=5 Participants	135 Count of participants n=7 Participants	271 Count of participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 40 to 52

Population: Intent to treat (ITT) Population comprised of all randomized participants who had a Baseline and at least one post Baseline schedule Hgb assessment.

The mean hemoglobin during the Evaluation Period was estimated by a statistical model.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)	10.89 Grams per deciliter (g/dL) Standard Error 0.062	10.83 Grams per deciliter (g/dL) Standard Error 0.060

SECONDARY outcome

Timeframe: Weeks 40 to 52

Population: Modified Intent to treat (mITT) comprised of all ITT participants who had at least one Hgb measurement during the evaluation period.

The percentage of participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Odds ratio was estimated using a logistic regression and provided along with its 95% CI and a one-sided p-value.

Outcome measures

Outcome measures
Measure	Daprodustat n=120 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=125 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) Responder	88 Percentage of participants	90 Percentage of participants
Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) Non-responder	13 Percentage of participants	10 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: ITT Population

Change from Baseline was calculated as the post-dose Week 4 visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Change From Baseline in Hgb (Hgb Increase Rate) at Week 4	-0.42 g/dL Standard Deviation 0.898	0.08 g/dL Standard Deviation 0.525

SECONDARY outcome

Timeframe: Week 4

Population: ITT Population. Data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency.

Percentage of participants within each category were provided only for daprodustat and the categories were classified into 6 (i.e., \<=-2, \>-2 to -1, \>-1 to 0, \>0 to 1, \>1 to 2, \>2 grams per deciliter \[g/dL\]). In addition, 'within 1.0 g/dL (i.e., \<=-1 and \>=1) and over 2.0 g/dL (i.e., \<-2 and \>2) categories were provided.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Percentage of Participants by Hgb Change From Baseline Category at Week 4 <= -2.0	5 Percentage of participants	—
Percentage of Participants by Hgb Change From Baseline Category at Week 4 > -2.0 and <= -1.0	21 Percentage of participants	—
Percentage of Participants by Hgb Change From Baseline Category at Week 4 > -1.0 and <= 0	44 Percentage of participants	—
Percentage of Participants by Hgb Change From Baseline Category at Week 4 > 0 and <= 1.0	27 Percentage of participants	—
Percentage of Participants by Hgb Change From Baseline Category at Week 4 > 1.0 and <= 2.0	4 Percentage of participants	—
Percentage of Participants by Hgb Change From Baseline Category at Week 4 > 2.0	0 Percentage of participants	—
Percentage of Participants by Hgb Change From Baseline Category at Week 4 within +/- 1.0	75 Percentage of participants	—
Percentage of Participants by Hgb Change From Baseline Category at Week 4 over +/- 2.0	5 Percentage of participants	—

SECONDARY outcome

Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44, and 48)

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Daprodustat. Median along with the interquartile range (25th and 75th percentile) has been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Distribution of Daprodustat Dose Level by Visit Day 1, n=133	4.0 milligrams per day (mg/day) Interval 4.0 to 4.0	—
Distribution of Daprodustat Dose Level by Visit Week 4, n=133	4.0 milligrams per day (mg/day) Interval 4.0 to 6.0	—
Distribution of Daprodustat Dose Level by Visit Week 8, n=126	4.0 milligrams per day (mg/day) Interval 4.0 to 6.0	—
Distribution of Daprodustat Dose Level by Visit Week 12, n=125	6.0 milligrams per day (mg/day) Interval 4.0 to 6.0	—
Distribution of Daprodustat Dose Level by Visit Week 16, n=123	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—
Distribution of Daprodustat Dose Level by Visit Week 20, n=123	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—
Distribution of Daprodustat Dose Level by Visit Week 24, n=123	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—
Distribution of Daprodustat Dose Level by Visit Week 28, n=123	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—
Distribution of Daprodustat Dose Level by Visit Week 32, n=122	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—
Distribution of Daprodustat Dose Level by Visit Week 36, n=121	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—
Distribution of Daprodustat Dose Level by Visit Week 40, n=119	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—
Distribution of Daprodustat Dose Level by Visit Week 44, n=117	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—
Distribution of Daprodustat Dose Level by Visit Week 48, n=117	6.0 milligrams per day (mg/day) Interval 4.0 to 8.0	—

SECONDARY outcome

Timeframe: Day 1, Weeks 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48, and 50

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Darbepoetin Alfa. Median along with the interquartile range (25th and 75th percentile) has been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=134 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Distribution of Darbepoetin Alfa Dose Level by Visit Day 1, n=134	15.0 micrograms per week (ug/week) Interval 15.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 2. n=134	15.0 micrograms per week (ug/week) Interval 15.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 4, n=134	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 6, n=133	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 8, n=131	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 10, n=129	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 12, n=129	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 14, n=129	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 16, n=129	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 18, n=129	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 20, n=129	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 22, n=128	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 24, n=129	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 26, n=129	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 28, n=127	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 30, n=128	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 32, n=127	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 34, n=127	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 36, n=127	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 38, n=127	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 40, n=125	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 42, n=125	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 44, n=125	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 46, n=125	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 48, n=124	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—
Distribution of Darbepoetin Alfa Dose Level by Visit Week 50, n=122	15.0 micrograms per week (ug/week) Interval 10.0 to 30.0	—

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT Population. Only those participants with data available at the time of assessment were used for analysis. Summary data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency. Median along with inter quartile range (25th and 75th percentile) have been presented.

Duration of treatment interruption due to Hgb \>13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for the daprodustat group.

Outcome measures

Outcome measures
Measure	Daprodustat n=3 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Duration of Treatment Interruption Due to Hgb >13 g/dL	28.0 Days Interval 28.0 to 56.0	—

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT Population. Summary data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency.

Number of dose adjustments has been presented only for daprodustat.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Number of Dose Adjustments for Daprodustat	2.0 Dose adjustments Interval 0.0 to 6.0	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Hgb Values at Each Assessment Visit Baseline (Day 1), n=133, 134	10.94 g/dL Standard Deviation 0.770	10.82 g/dL Standard Deviation 0.732
Hgb Values at Each Assessment Visit Week 4, n=133, 134	10.52 g/dL Standard Deviation 0.984	10.90 g/dL Standard Deviation 0.829
Hgb Values at Each Assessment Visit Week 8, n=127, 132	10.50 g/dL Standard Deviation 1.069	11.01 g/dL Standard Deviation 0.824
Hgb Values at Each Assessment Visit Week 12, n=125, 129	10.53 g/dL Standard Deviation 0.989	11.09 g/dL Standard Deviation 0.753
Hgb Values at Each Assessment Visit Week 16, n=124, 129	10.57 g/dL Standard Deviation 0.970	10.92 g/dL Standard Deviation 0.862
Hgb Values at Each Assessment Visit Week 20, n=123, 129	10.85 g/dL Standard Deviation 0.784	10.95 g/dL Standard Deviation 0.830
Hgb Values at Each Assessment Visit Week 24, n=123, 129	11.01 g/dL Standard Deviation 0.718	10.92 g/dL Standard Deviation 0.859
Hgb Values at Each Assessment Visit Week 28, n=123, 129	10.97 g/dL Standard Deviation 0.748	10.86 g/dL Standard Deviation 0.872
Hgb Values at Each Assessment Visit Week 32, n=122, 127	11.10 g/dL Standard Deviation 0.829	10.96 g/dL Standard Deviation 0.820
Hgb Values at Each Assessment Visit Week 36, n=121, 127	11.12 g/dL Standard Deviation 0.827	10.91 g/dL Standard Deviation 0.847
Hgb Values at Each Assessment Visit Week 40, n=120, 125	10.97 g/dL Standard Deviation 0.860	10.90 g/dL Standard Deviation 0.835
Hgb Values at Each Assessment Visit Week 44, n=117, 125	10.98 g/dL Standard Deviation 0.912	10.87 g/dL Standard Deviation 0.904
Hgb Values at Each Assessment Visit Week 48, n=117, 124	10.94 g/dL Standard Deviation 0.893	10.76 g/dL Standard Deviation 0.830
Hgb Values at Each Assessment Visit Week 52,n=115, 120	10.79 g/dL Standard Deviation 0.807	10.79 g/dL Standard Deviation 0.841

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calcuated as the post-dose visit value minus the Baseline value. Change from Baseline Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Change From Baseline in Hgb Values at Each Assessment Visit Week 4, n=133, 134	-0.42 g/dL Standard Deviation 0.898	0.08 g/dL Standard Deviation 0.525
Change From Baseline in Hgb Values at Each Assessment Visit Week 8, n=127, 132	-0.45 g/dL Standard Deviation 1.178	0.20 g/dL Standard Deviation 0.821
Change From Baseline in Hgb Values at Each Assessment Visit Week 12, n=125, 129	-0.42 g/dL Standard Deviation 1.258	0.27 g/dL Standard Deviation 1.021
Change From Baseline in Hgb Values at Each Assessment Visit Week 16, n=124, 129	-0.38 g/dL Standard Deviation 1.348	0.09 g/dL Standard Deviation 1.146
Change From Baseline in Hgb Values at Each Assessment Visit Week 20, n=123, 129	-0.09 g/dL Standard Deviation 1.161	0.12 g/dL Standard Deviation 1.120
Change From Baseline in Hgb Values at Each Assessment Visit Week 24, n=123, 129	0.07 g/dL Standard Deviation 1.106	0.10 g/dL Standard Deviation 1.068
Change From Baseline in Hgb Values at Each Assessment Visit Week 28, n=123, 129	0.03 g/dL Standard Deviation 1.084	0.04 g/dL Standard Deviation 1.080
Change From Baseline in Hgb Values at Each Assessment Visit Week 32, n=122, 127	0.16 g/dL Standard Deviation 1.119	0.14 g/dL Standard Deviation 1.071
Change From Baseline in Hgb Values at Each Assessment Visit Week 36, n=121, 127	0.17 g/dL Standard Deviation 1.020	0.09 g/dL Standard Deviation 1.041
Change From Baseline in Hgb Values at Each Assessment Visit Week 40, n=120, 125	0.03 g/dL Standard Deviation 1.060	0.10 g/dL Standard Deviation 1.034
Change From Baseline in Hgb Values at Each Assessment Visit Week 44, n=117, 125	0.03 g/dL Standard Deviation 1.118	0.07 g/dL Standard Deviation 1.019
Change From Baseline in Hgb Values at Each Assessment Visit Week 48, n=117, 124	-0.01 g/dL Standard Deviation 1.164	-0.04 g/dL Standard Deviation 0.978
Change From Baseline in Hgb Values at Each Assessment Visit Week 52,n=115, 120	-0.16 g/dL Standard Deviation 1.169	0.01 g/dL Standard Deviation 1.019

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Percentage of participants with Hgb within the target range was summarized at each assessment visit by treatment group have been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Baseline (Day 1), n=133, 134	79 Percentage of participants	87 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 4, n=133,134	65 Percentage of participants	80 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 8, n=127,132	65 Percentage of participants	84 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 12, n=125,129	66 Percentage of participants	86 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 16, n=124,129	64 Percentage of participants	80 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 20, n=123,129	82 Percentage of participants	81 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 24, n=123,129	85 Percentage of participants	81 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 28, n=123,129	85 Percentage of participants	82 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 32, n=122, 127	79 Percentage of participants	80 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 36, n=121,127	78 Percentage of participants	78 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 40, n=120,125	77 Percentage of participants	80 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 44, n=117,125	74 Percentage of participants	82 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 48, n=117,124	77 Percentage of participants	79 Percentage of participants
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit Week 52, n=115,120	77 Percentage of participants	80 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 40 to 52

Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.

Percentage of time in Hgb target range (10.0 to 12.0 g/dL) during the primary efficacy evaluation period (Weeks 40 to 52) for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=118 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=125 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Percentage of Time in Hgb Target Range (10.0 to 12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)	76.81 Percentage of time Standard Deviation 30.387	80.23 Percentage of time Standard Deviation 28.038

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT Population

If an initial Hgb value was less than 7.5 g/dL, measurement was repeated at the same study visit (using the same sample) to calculate the average. If the average met the Hgb stopping criteria, study treatment was permanently discontinued. Number of participants who had an Hgb level of less than 7.5 g/dL has been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT Population

Number of participants who had an Hgb increase of more than 2 g/dL over any 4 weeks for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT Population

Number of participants who had an Hgb increase of more than 13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL	7 Percentage of participants	8 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT Population

Number of episodes with Hgb level of more than 13.0 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.

Outcome measures

Outcome measures
Measure	Daprodustat n=133 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=134 Participants Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Number of Episodes With Hgb Level of More Than 13.0 g/dL	9 Episodes	12 Episodes

SECONDARY outcome

Timeframe: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24

Population: PK Population

Blood samples for Pharmacokinetic (PK) analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). NA indicates geometric co-efficient of variation could not be calculated as a single participant was analyzed. Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. PK population comprised of all daprodustat-treated participants from whom PK samples were collected and analyzed. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data.

Outcome measures

Outcome measures
Measure	Daprodustat n=125 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat 1 mg, n=8	27.57 Hours*nanograms per milliliter Geometric Coefficient of Variation 147.6	—
Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat 2 mg, n=24	44.52 Hours*nanograms per milliliter Geometric Coefficient of Variation 139.2	—
Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat 4 mg, n=91	72.68 Hours*nanograms per milliliter Geometric Coefficient of Variation 242.2	—
Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat 6 mg, n=61	140.58 Hours*nanograms per milliliter Geometric Coefficient of Variation 238.9	—
Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat 8 mg, n=38	170.41 Hours*nanograms per milliliter Geometric Coefficient of Variation 136.1	—
Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat 12 mg, n=17	150.53 Hours*nanograms per milliliter Geometric Coefficient of Variation 176.4	—
Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat 18 mg, n=5	488.93 Hours*nanograms per milliliter Geometric Coefficient of Variation 89.2	—

SECONDARY outcome

Timeframe: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24

Population: PK Population

Blood samples for PK analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data.

Outcome measures

Outcome measures
Measure	Daprodustat n=125 Participants Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Maximum Concentration (Cmax) of Plasma Daprodustat 1 mg, n=8	16.11 Nanograms per milliliter Geometric Coefficient of Variation 105.7	—
Maximum Concentration (Cmax) of Plasma Daprodustat 2 mg, n=24	25.16 Nanograms per milliliter Geometric Coefficient of Variation 122.7	—
Maximum Concentration (Cmax) of Plasma Daprodustat 4 mg, n=91	42.45 Nanograms per milliliter Geometric Coefficient of Variation 237.9	—
Maximum Concentration (Cmax) of Plasma Daprodustat 6 mg, n=61	83.60 Nanograms per milliliter Geometric Coefficient of Variation 269.7	—
Maximum Concentration (Cmax) of Plasma Daprodustat 8 mg, n=38	105.71 Nanograms per milliliter Geometric Coefficient of Variation 110.9	—
Maximum Concentration (Cmax) of Plasma Daprodustat 12 mg, n=17	108.58 Nanograms per milliliter Geometric Coefficient of Variation 117.8	—
Maximum Concentration (Cmax) of Plasma Daprodustat 18 mg, n=5	306.61 Nanograms per milliliter Geometric Coefficient of Variation 61.0	—

Adverse Events

Daprodustat

Serious events: 21 serious events

Other events: 102 other events

Deaths: 0 deaths

Darbepoetin Alfa

Serious events: 37 serious events

Other events: 102 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Daprodustat n=136 participants at risk Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.	Darbepoetin Alfa n=135 participants at risk Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Infections and infestations Nasopharyngitis	41.9% 57/136 • Number of events 110 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	54.1% 73/135 • Number of events 135 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Infections and infestations Pharyngitis	7.4% 10/136 • Number of events 11 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	4.4% 6/135 • Number of events 6 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Infections and infestations Gastroenteritis	5.1% 7/136 • Number of events 7 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	1.5% 2/135 • Number of events 2 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Injury, poisoning and procedural complications Shunt stenosis	11.8% 16/136 • Number of events 30 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	11.1% 15/135 • Number of events 28 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Injury, poisoning and procedural complications Contusion	12.5% 17/136 • Number of events 21 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	7.4% 10/135 • Number of events 12 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Injury, poisoning and procedural complications Skin abrasion	7.4% 10/136 • Number of events 14 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	5.2% 7/135 • Number of events 7 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Injury, poisoning and procedural complications Procedural hypotension	8.1% 11/136 • Number of events 16 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	3.7% 5/135 • Number of events 6 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Gastrointestinal disorders Diarrhoea	14.7% 20/136 • Number of events 24 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	8.9% 12/135 • Number of events 15 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Gastrointestinal disorders Vomiting	11.0% 15/136 • Number of events 20 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	8.1% 11/135 • Number of events 13 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Gastrointestinal disorders Nausea	6.6% 9/136 • Number of events 10 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	8.1% 11/135 • Number of events 13 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Gastrointestinal disorders Constipation	5.9% 8/136 • Number of events 10 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	4.4% 6/135 • Number of events 6 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Gastrointestinal disorders Abdominal discomfort	2.2% 3/136 • Number of events 3 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	5.2% 7/135 • Number of events 7 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Musculoskeletal and connective tissue disorders Back pain	4.4% 6/136 • Number of events 6 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	7.4% 10/135 • Number of events 10 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	3.7% 5/136 • Number of events 5 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	7.4% 10/135 • Number of events 13 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Musculoskeletal and connective tissue disorders Muscle spasms	5.1% 7/136 • Number of events 9 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	3.0% 4/135 • Number of events 5 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	0.74% 1/136 • Number of events 1 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	6.7% 9/135 • Number of events 10 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Nervous system disorders Headache	5.9% 8/136 • Number of events 8 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	4.4% 6/135 • Number of events 8 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
Vascular disorders Hypertension	3.7% 5/136 • Number of events 9 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	5.9% 8/135 • Number of events 8 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
General disorders Pyrexia	5.1% 7/136 • Number of events 8 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.	2.2% 3/135 • Number of events 4 • Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54]) Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.