Trial Outcomes & Findings for KRX-0502 (Ferric Citrate) in Subjects With NDD-CKD and IDA (The COMPASS Trial) (NCT NCT03236246)

Last Updated: 2021-03-12

Results Overview

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from a mixed model of repeated measures (MMRM), including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

206 participants

Primary outcome timeframe

Baseline; Week 24

Results posted on

2021-03-12

Participant Flow

Participant milestones

Participant milestones
Measure	KRX-0502 3 g/Day Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
24-Week Dose Titration Period STARTED	104	102
24-Week Dose Titration Period COMPLETED	80	75
24-Week Dose Titration Period NOT COMPLETED	24	27
24-Week Dose Maintenance Period STARTED	76	72
24-Week Dose Maintenance Period COMPLETED	73	66
24-Week Dose Maintenance Period NOT COMPLETED	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	KRX-0502 3 g/Day Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
24-Week Dose Titration Period Withdrawal by Subject	8	7
24-Week Dose Titration Period Lost to Follow-up	0	2
24-Week Dose Titration Period Study Drug Non-Compliance	3	2
24-Week Dose Titration Period Investigator Judgement	1	1
24-Week Dose Titration Period Prohibited Therapy	1	1
24-Week Dose Titration Period Start Chronic Dialysis/Kidney Transplant	0	1
24-Week Dose Titration Period Death	3	1
24-Week Dose Titration Period Protocol Violation	0	2
24-Week Dose Titration Period Adverse Event	7	8
24-Week Dose Titration Period Captured as Other	1	2
24-Week Dose Maintenance Period Withdrawal by Subject	1	3
24-Week Dose Maintenance Period Lost to Follow-up	1	1
24-Week Dose Maintenance Period Prohibited Therapy	1	0
24-Week Dose Maintenance Period Death	0	1
24-Week Dose Maintenance Period Adverse Event	0	1

Baseline Characteristics

Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KRX-0502 3 g/Day n=104 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=101 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	Total n=205 Participants Total of all reporting groups
Age, Continuous	68.3 years STANDARD_DEVIATION 11.22 • n=104 Participants	69.9 years STANDARD_DEVIATION 9.81 • n=101 Participants	69.1 years STANDARD_DEVIATION 10.55 • n=205 Participants
Sex: Female, Male Female	67 Participants n=104 Participants	69 Participants n=101 Participants	136 Participants n=205 Participants
Sex: Female, Male Male	37 Participants n=104 Participants	32 Participants n=101 Participants	69 Participants n=205 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=104 Participants	1 Participants n=101 Participants	1 Participants n=205 Participants
Race (NIH/OMB) Asian	1 Participants n=104 Participants	1 Participants n=101 Participants	2 Participants n=205 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=104 Participants	0 Participants n=101 Participants	0 Participants n=205 Participants
Race (NIH/OMB) Black or African American	32 Participants n=104 Participants	40 Participants n=101 Participants	72 Participants n=205 Participants
Race (NIH/OMB) White	68 Participants n=104 Participants	57 Participants n=101 Participants	125 Participants n=205 Participants
Race (NIH/OMB) More than one race	0 Participants n=104 Participants	0 Participants n=101 Participants	0 Participants n=205 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=104 Participants	2 Participants n=101 Participants	5 Participants n=205 Participants
Age, Continous: Dose Maintenance Period	67.6 years STANDARD_DEVIATION 11.57 • n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	69.6 years STANDARD_DEVIATION 8.94 • n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	68.6 years STANDARD_DEVIATION 10.38 • n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Sex: Female, Male: Dose Maintenance Period Female	46 Participants n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	48 Participants n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	94 Participants n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Sex: Female, Male: Dose Maintenance Period Male	30 Participants n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	24 Participants n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	54 Participants n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Race (NIH/OMB): Dose Maintenance Period American Indian or Alaska Native	0 Participants n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	1 Participants n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	1 Participants n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Race (NIH/OMB): Dose Maintenance Period Asian	1 Participants n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	0 Participants n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	1 Participants n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Race (NIH/OMB): Dose Maintenance Period Native Hawaiian or Other Pacific Islander	0 Participants n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	0 Participants n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	0 Participants n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Race (NIH/OMB): Dose Maintenance Period Black or African American	26 Participants n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	29 Participants n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	55 Participants n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Race (NIH/OMB): Dose Maintenance Period White	48 Participants n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	40 Participants n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	88 Participants n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Race (NIH/OMB): Dose Maintenance Period Unknown or Not Reported	1 Participants n=76 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	2 Participants n=72 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.	3 Participants n=148 Participants • Baseline data are reported for the Dose Maintenance Period, a subset of participants in the Safety Analysis Set starting the Dose Titration Period.
Hemoglobin	10.40 grams per deciliter (g/dL) STANDARD_DEVIATION 0.749 • n=97 Participants • Data are reported for Per-Protocol Analysis Set members, comprised of participants in the Full Analysis Set (FAS) (randomized participants who took \>=1 dose of study medication and had \>=1 post-randomization efficacy measurement) who met the study eligibility requirements and had no major protocol deviations that affected the validity of the efficacy measurements.	10.51 grams per deciliter (g/dL) STANDARD_DEVIATION 0.739 • n=86 Participants • Data are reported for Per-Protocol Analysis Set members, comprised of participants in the Full Analysis Set (FAS) (randomized participants who took \>=1 dose of study medication and had \>=1 post-randomization efficacy measurement) who met the study eligibility requirements and had no major protocol deviations that affected the validity of the efficacy measurements.	10.45 grams per deciliter (g/dL) STANDARD_DEVIATION 0.744 • n=183 Participants • Data are reported for Per-Protocol Analysis Set members, comprised of participants in the Full Analysis Set (FAS) (randomized participants who took \>=1 dose of study medication and had \>=1 post-randomization efficacy measurement) who met the study eligibility requirements and had no major protocol deviations that affected the validity of the efficacy measurements.

PRIMARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set: participants in the Full Analysis Set (FAS) (randomized par. who took \>=1 dose of study medication and had \>=1 post-randomization efficacy measurement) who met the study eligibility requirements and had no major protocol deviations that affected the validity of the efficacy measurements. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=74 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=70 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Hemoglobin (Hgb) at Week 24	0.73 grams per deciliter (g/dL) Standard Error 0.101	0.70 grams per deciliter (g/dL) Standard Error 0.104

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=67 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=61 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Hgb at Week 48	0.61 g/dL Standard Error 0.114	0.58 g/dL Standard Error 0.119

SECONDARY outcome

Timeframe: from Randomization to Week 24

Population: Per-Protocol Analysis Set. Only participants with data available at Week 24 were analyzed. A participant's time to first hemoglobin value \>= 0.5 above the Baseline value was censored at the study day of the participant's last hemoglobin assessment on or before the Week 24 visit.

The Kaplan-Meier estimator of the survival function of time from randomization to the first increase from Baseline Hgb of at least 0.5 g/dL for each of the two starting dose treatment groups were obtained.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=99 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=90 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Time From Randomization to the First Increase From Baseline Hgb of at Least 0.5 Grams Per Deciliter (g/dL) During the Dose Titration Period	84.0 days Interval 57.0 to 89.0	57.0 days Interval 29.0 to 85.0

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=75 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=69 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Transferrin Saturation (TSAT) at Week 24	6.30 percentage of transferrin saturation Standard Error 1.023	6.85 percentage of transferrin saturation Standard Error 1.073

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=68 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=61 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in TSAT at Week 48	7.97 percentage of transferrin saturation Standard Error 1.053	10.63 percentage of transferrin saturation Standard Error 1.113

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=75 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=70 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Ferritin at Week 24	136.63 nanograms per millilier (ng/mL) Standard Error 13.315	155.28 nanograms per millilier (ng/mL) Standard Error 14.037

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=69 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=62 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Ferritin at Week 48	251.44 ng/mL Standard Error 29.417	343.27 ng/mL Standard Error 31.148

SECONDARY outcome

Timeframe: Baseline; up to Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=76 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=68 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Serum Phosphate at Week 24	-0.19 milligrams per deciliter (mg/dL) Standard Error 0.065	-0.25 milligrams per deciliter (mg/dL) Standard Error 0.069

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=69 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=62 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Serum Phosphate at Week 48	-0.07 mg/dL Standard Error 0.075	-0.20 mg/dL Standard Error 0.079

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=76 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=68 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24	-1.08 ml/minute/1.73 meters cubed (m^3) Standard Error 0.836	-1.53 ml/minute/1.73 meters cubed (m^3) Standard Error 0.0882

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=70 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=62 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in eGFR at Week 48	-1.85 ml/minute/1.73 m^3 Standard Error 0.977	-2.20 ml/minute/1.73 m^3 Standard Error 1.035

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=76 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=68 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Bicarbonate at Week 24	-0.15 milliquivalent (mEq)/Liter (L) Standard Error 0.296	-0.05 milliquivalent (mEq)/Liter (L) Standard Error 0.312

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=69 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=62 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Bicarbonate at Week 48	0.03 mEq/L Standard Error 0.328	-0.51 mEq/L Standard Error 0.345

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using a common slope analysis of covariance (ANCOVA) model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, and a random error term.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=71 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=68 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Intact Parathyroid Hormone (iPTH) at Week 24	1.64 picograms per milliliter (pg/mL) Standard Error 4.547	0.39 picograms per milliliter (pg/mL) Standard Error 4.647

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants who completed their Week 48 Visit were included in this analysis.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=69 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=59 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in iPTH at Week 48	-1.49 pg/mL Standard Error 5.385	5.74 pg/mL Standard Error 5.824

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=67 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=67 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in C-terminal Fibroblast Growth Factor 23 (FGF23) at Week 24	-94.78 relative units (RU)/mL Standard Error 26.393	-63.22 relative units (RU)/mL Standard Error 26.392

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants who completed their Week 48 Visit were included in this analysis.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=65 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=58 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in C-terminal FGF23 at Week 48	-85.70 RU/mL Standard Error 23.029	-80.34 RU/mL Standard Error 24.370

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using a common slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, and a random error term.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=70 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=67 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 24	-0.23 pg/mL Standard Error 8.106	-2.01 pg/mL Standard Error 8.286

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants who completed their Week 48 Visit are included in this analysis.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=69 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=58 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 48	18.52 pg/mL Standard Error 14.741	10.15 pg/mL Standard Error 16.086

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data who were currently employed (working for pay) were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=10 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=11 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures Percent Work Time Missed	0.00 percentage of score Standard Deviation 0.000	-3.19 percentage of score Standard Deviation 9.222
Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures Percent Impairment while Working	-15.00 percentage of score Standard Deviation 25.884	4.00 percentage of score Standard Deviation 30.258
Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures Percent Overall Work Impairment	-15.00 percentage of score Standard Deviation 25.884	1.40 percentage of score Standard Deviation 26.842

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data who were currently employed (working for pay) were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=14 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=11 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures Percent Work Time Missed	0.00 percentage of score Standard Deviation 0.000	-3.48 percentage of score Standard Deviation 7.412
Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures Percent Impairment while Working	-11.43 percentage of score Standard Deviation 16.762	7.78 percentage of score Standard Deviation 29.486
Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures Percent Overall Work Impairment	-11.43 percentage of score Standard Deviation 16.762	4.71 percentage of score Standard Deviation 24.601

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=76 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=71 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 24: Activity Impairment	-18.03 percentage of score Standard Deviation 28.753	-6.34 percentage of score Standard Deviation 31.769

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=70 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=61 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Activity Impairment	-16.71 percentage of score Standard Deviation 36.859	-6.72 percentage of score Standard Deviation 36.227

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Participants were asked to respond to 13 statements (as they apply to the last 7 days) that other people with the same illness said are important with one of the following: 0, not at all; 1, a little bit; 2, somewhat; 3, quite a bit; 4, very much. All individual items were summed to create a single fatigue score ranging from 0 to 52. Higher scores indicate greater fatigue.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=77 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=72 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Score at Week 24	7.22 score on a scale Standard Deviation 10.986	4.35 score on a scale Standard Deviation 10.047

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=69 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=62 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue Scale Score at Week 48	7.49 score on a scale Standard Deviation 11.817	3.68 score on a scale Standard Deviation 9.954

SECONDARY outcome

Timeframe: up to Week 48

Population: Per-Protocol Analysis Set

A hospitalization is defined as admission to the hospital.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=97 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=86 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Number of Hospitalizations for Participants Who Entered the Dose Maintenance Period	13 hospitalizations	10 hospitalizations

SECONDARY outcome

Timeframe: up to Week 48

Population: Per-Protocol Analysis Set

A hospitalization is defined as admission to the hospital.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=13 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=10 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Duration of Hospitalizations for Participants Who Entered the Dose Maintenance Period	4.08 days Standard Deviation 2.499	3.91 days Standard Deviation 0.980

SECONDARY outcome

Timeframe: up to Week 48

Population: Safety Analysis Set: all participants who took at least 1 dose of study medication

Treatment-emergent adverse events are defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication.

Outcome measures

Outcome measures
Measure	KRX-0502 3 g/Day n=104 Participants Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=101 Participants Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) for Participants Who Entered the Dose Maintenance Period	89 Participants	89 Participants

Adverse Events

KRX-0502 3 g/Day

Serious events: 26 serious events

Other events: 58 other events

Deaths: 3 deaths

KRX-0502 4 g/Day

Serious events: 25 serious events

Other events: 59 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	KRX-0502 3 g/Day n=104 participants at risk Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.	KRX-0502 4 g/Day n=101 participants at risk Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12.
Gastrointestinal disorders Constipation	16.3% 17/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	11.9% 12/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.
Gastrointestinal disorders Diarrhoea	12.5% 13/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	14.9% 15/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.
Gastrointestinal disorders Faeces discoloured	15.4% 16/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	9.9% 10/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.
Infections and infestations Urinary tract infection	14.4% 15/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	10.9% 11/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.
Vascular disorders Hypertension	11.5% 12/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	10.9% 11/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.
Gastrointestinal disorders Nausea	7.7% 8/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	10.9% 11/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.
General disorders Oedema peripheral	4.8% 5/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	8.9% 9/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.
Gastrointestinal disorders Vomiting	1.9% 2/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	7.9% 8/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.
Nervous system disorders Dizziness	5.8% 6/104 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.	0.99% 1/101 • from the time of informed consent up to 48 weeks Treatment-emergent adverse events, defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication, were collected in members of the Safety Analysis Set (comprised as all participants who took at least 1 dose of study medication). Data are reported for those participants who entered the Dose Maintenance Period.

Additional Information

Keryx Medical Information

Keryx

Phone: 1-844-44-KERYX (844-445-3799)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER