Trial Outcomes & Findings for Transition to Ferric Citrate Among Hemodialysis and Peritoneal Dialysis Patients (NCT NCT03079869)

Last Updated: 2022-01-13

Results Overview

Serum phosphorus levels measured by mg/dL from the 6 months prior to enrollment were compared to serum phosphorus levels collected during the 6 months of ferric citrate use

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

55 participants

Primary outcome timeframe

6 months

Results posted on

2022-01-13

Participant Flow

Study subjects who received either hemodialysis (HD) or peritoneal dialysis (PD) at Kaiser Permanente Southern California, Los Angeles Medical Center were eligible for recruitment.

No pre-assignment events. 55 subjects were enrolled.

Participant milestones

Participant milestones
Measure	Ferric Citrate - Hemodialysis Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Overall Study STARTED	28	27
Overall Study COMPLETED	15	16
Overall Study NOT COMPLETED	13	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Ferric Citrate - Hemodialysis Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Overall Study Adverse Event	6	8
Overall Study Withdrawal by Subject	4	1
Overall Study Protocol withdrawal criteria-off drug > 2 weeks	3	2

Baseline Characteristics

Transition to Ferric Citrate Among Hemodialysis and Peritoneal Dialysis Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ferric Citrate - Hemodialysis n=21 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis n=26 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Total n=47 Participants Total of all reporting groups
Age, Continuous	65 years STANDARD_DEVIATION 13 • n=5 Participants	57 years STANDARD_DEVIATION 14 • n=7 Participants	60 years STANDARD_DEVIATION 14 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	19 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Asian	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized African American	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	14 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized Unknown Race	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Unknown Ethnicity	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	26 participants n=7 Participants	47 participants n=5 Participants
Body Mass Index (BMI)	28.4 kg/m^2 STANDARD_DEVIATION 4.7 • n=5 Participants	27.8 kg/m^2 STANDARD_DEVIATION 5.2 • n=7 Participants	28.1 kg/m^2 STANDARD_DEVIATION 4.9 • n=5 Participants
Smoking	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Duration on Dialysis	29 months STANDARD_DEVIATION 32.1 • n=5 Participants	41.4 months STANDARD_DEVIATION 49.2 • n=7 Participants	36.2 months STANDARD_DEVIATION 42.5 • n=5 Participants
Diabetes	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Cerebrovascular Disease	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Congestive Heart Failure	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ischemic Heart Failure	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Peripheral Vascular Disease	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The final analysis included 21 Hemodialysis and 26 Peritoneal Dialysis patients after exclusion of early dropouts. Wilcoxon signed rank test was used to compare pre-treatment and on-treatment

Serum phosphorus levels measured by mg/dL from the 6 months prior to enrollment were compared to serum phosphorus levels collected during the 6 months of ferric citrate use

Outcome measures

Outcome measures
Measure	Ferric Citrate - Hemodialysis n=21 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis n=26 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Phosphorus Levels Pre-treatment	5.3 mg/dL Standard Deviation 1	5.6 mg/dL Standard Deviation 0.8
Phosphorus Levels On-treatment	5.4 mg/dL Standard Deviation 1.1	6 mg/dL Standard Deviation 1.8

SECONDARY outcome

Timeframe: 6 months

The amount of intravenous (IV) iron in mg used per month by participants for 6 months before and 6 months on Ferric Citrate treatment.

Outcome measures

Outcome measures
Measure	Ferric Citrate - Hemodialysis n=21 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis n=26 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Intravenous (IV) Iron Pre-Treatment	249.2 mg/mo Standard Deviation 215.6	21.2 mg/mo Standard Deviation 43.1
Intravenous (IV) Iron On-Treatment	102 mg/mo Standard Deviation 137.5	11.6 mg/mo Standard Deviation 33.7

SECONDARY outcome

Timeframe: 6 months

Mean Erythropoiesis Stimulating Agents (ESA) use from the 6 months prior to enrollment were compared to ESA use during the 6 months of ferric citrate use. The mean ESA dose units given to each participant per month was used in the analysis of this outcome.

Outcome measures

Outcome measures
Measure	Ferric Citrate - Hemodialysis n=21 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis n=26 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Erythropoiesis Stimulating Agents (ESA) Dose Pre-Treatment	28761.1 units/mo Standard Deviation 41314.1	16724.4 units/mo Standard Deviation 14042.3
Erythropoiesis Stimulating Agents (ESA) Dose Post-Treatment	16525.8 units/mo Standard Deviation 16917	16780.1 units/mo Standard Deviation 13433.7

SECONDARY outcome

Timeframe: 6 months

Population: The final analysis included 21 Hemodialysis and 26 Peritoneal Dialysis patients after exclusion of early dropouts.

median pill count of ferric citrate pills/day required to maintain phosphorus control

Outcome measures

Outcome measures
Measure	Ferric Citrate - Hemodialysis n=21 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis n=26 Participants Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Median Pill Count Phosphate binder pill count prior to Ferric Citrate use	9.5 tablets per day Interval 6.8 to 13.8	6 tablets per day Interval 6.0 to 9.0
Median Pill Count Phosphate binder pill count during Ferric Citrate use	6.0 tablets per day Interval 4.5 to 9.0	4.5 tablets per day Interval 2.0 to 6.0

Adverse Events

Ferric Citrate - Hemodialysis

Serious events: 7 serious events

Other events: 23 other events

Deaths: 0 deaths

Ferric Citrate - Peritoneal Dialysis

Serious events: 10 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ferric Citrate - Hemodialysis n=27 participants at risk Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis n=27 participants at risk Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Gastrointestinal disorders Black stool	74.1% 20/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	92.6% 25/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Gastrointestinal disorders Diarrhea	37.0% 10/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	37.0% 10/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Gastrointestinal disorders Constipation	14.8% 4/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	18.5% 5/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Gastrointestinal disorders Bloating/Gas	7.4% 2/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	7.4% 2/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Gastrointestinal disorders Abdominal pain	3.7% 1/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	7.4% 2/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Gastrointestinal disorders Nausea, vomiting	3.7% 1/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	14.8% 4/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	11.1% 3/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Skin and subcutaneous tissue disorders Itching/rash	7.4% 2/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	14.8% 4/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	7.4% 2/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	14.8% 4/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Renal and urinary disorders Urinary Tract Infection	3.7% 1/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Infections and infestations Abscess	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
General disorders Peritonitis	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Cardiac disorders Chest Pain/Palpitations	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
General disorders Fatigue	7.4% 2/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.

Additional Information

KPSC PRS Administrator

Kaiser Permanente

Phone: 626-720-7463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ferric Citrate - Hemodialysis n=27 participants at risk Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.	Ferric Citrate - Peritoneal Dialysis n=27 participants at risk Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Blood and lymphatic system disorders Arteriovenous fistula	7.4% 2/27 • Number of events 2 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Cardiac disorders Congestive heart failure exacerbation	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Gastrointestinal disorders gallstone pancreatitis	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Gastrointestinal disorders Gastrointestinal Hemorrhage	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Gastrointestinal disorders Hematochezia	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
General disorders Abdominal swelling	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
General disorders Peritonitis	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Infections and infestations Right foot infection	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Musculoskeletal and connective tissue disorders Chest pain	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Musculoskeletal and connective tissue disorders Chronic back pain	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Musculoskeletal and connective tissue disorders Intertrochanteric fracture	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Musculoskeletal and connective tissue disorders Left foot pain	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Musculoskeletal and connective tissue disorders Right hip osteoporotic Fracture	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Renal and urinary disorders Laparoscopic right nephrectomy	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Renal and urinary disorders Placement of catheter for HD	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Respiratory, thoracic and mediastinal disorders Right sided pleuroperitoneal leak	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Skin and subcutaneous tissue disorders Left heel ulcers	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Vascular disorders Critical limb ischemia	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Vascular disorders Hemorrhagic cerebrovascular accident	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.
Vascular disorders Peripheral vascular disease	3.7% 1/27 • Number of events 1 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.	0.00% 0/27 • 7 months Adverse event (AE's) were included for all patient who received study drug for at least 1 day (n=54). After the baseline visit adverse events are collected on a weekly basis for the hemodialysis patients, and on a bi-monthly basis from the dialysis patients, and again 30days after the termination of the study.