Randomized, Controlled, Double-blind Multicenter Safety Study to Evaluate the Safety and Immunogenicity of Subcutaneous EPO HEXAL vs. ERYPO® in the Treatment of Anemia Associated With Chronic Renal Insufficiency in Predialysis Patients

• Sponsor: Sandoz (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00701714
• Collaborator: (none)
• Enrollment: 337
• Locations: 123
• Arms: 2
• Duration (Months): 28
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a randomized, controlled, double-blind, multicenter multinational safety study involving about 300 predialysis patients aged 18 years or above suffering from anemia.

Symptomatic anemia will be corrected by s.c. application of EPO HEXAL or ERYPO® in order to achieve a hemoglobin target range of 10.0 -12.0 g/dL.

Condition or Disease	Intervention/Treatment	Phase
Anemia; Chronic Renal Insufficiency	Drug: HX575 recombinant human erythropoietin alfa; Drug: ERYPO	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 337 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Controlled, Double-blind Multicenter Safety Study to Evaluate the Safety and Immunogenicity of Subcutaneous EPO HEXAL vs. ERYPO® in the Treatment of Anemia Associated With Chronic Renal Insufficiency in Predialysis Patients
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 HX575, EPO HEXAL	Drug: HX575 recombinant human erythropoietin alfa; Solution for injection (s.c.)
Active Comparator: 2 ERYPO	Drug: ERYPO; Solution for injection (s.c.)

Outcome Measures

Primary Outcome Measures

1. Change in Hemoglobin Level [13 weeks]

   Mean absolute change in hemoglobin (baseline to end of study week 13)

2. Weekly Epoetin Dose [weeks 11-13]

   Mean weekly epoetin dose [IU/kg] in study weeks 11-13

Secondary Outcome Measures

1. Immunogenicity [13 weeks]

   Number of participants with antibody formation against Epoetin during treatment period (safety set)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Known chronic renal insufficiency of at least 4 weeks duration; CKD stage at least 3 or higher

• Male and female patients, age: >=18

• Patients who are naïve to ESA treatment or previously ESA treated after 3 months of ESA-free period (i.v. or s.c.)

• Patients with symptomatic anemia, defined as Hb level below 11.0 g/dL and not lower than or equal to 7.5 g/dL on at least 2 visits during the screening period

• Adequate iron status, serum ferritin >= 100 µg/L or transferrin saturation >= 20%

• Ability to follow study instructions and likely to complete all required visits and compliant with subcutaneous administration

• Written informed consent of the patient.

Exclusion Criteria:

• Anemia of non-renal causes

• Therapy with immunosuppressants (other than corticosteroids for chronic treatment) within 3 months before screening and during the study for patients with renal allograft in place or other chronic conditions (e.g. lupus erythematosus, rheumatic arthritis)

• Patients previously treated with chronic dialysis within the last 6 months (exception: one session of acute dialysis)

• Patients with acute deterioration of renal function during the screening phase according to the investigator's judgment

• Patients receiving any RBC/whole blood transfusion during the screening period

• Primary hematological disorder (e.g. myeloma, myelodysplastic syndrome, sickle cell anemia, hematological malignancy, hemolytic anemia)

• Evidence of uncontrolled diabetes mellitus (HbA1c > 10 % at visit -2)

• Evidence of severe hepatic dysfunction (e.g. ALT and/or AST above 2x upper limit of normal range; or gamma-GT above 3x upper limit of normal range)

• Clinical evidence of current uncontrolled or symptomatic hyperparathyroidism, defined as parathyroid hormone > 500 ng/L at visit -2.

• Uncontrolled hypertension, defined as a systolic blood pressure of >= 160 mmHg and a diastolic blood pressure measurement >= 100 mmHg (average of two values with at least one day between measurements)

• Congestive heart failure and/or angina pectoris [New York Heart Association (NYHA) class III and IV]

• History of stroke or myocardial infarction during the last 6 months prior to visit -2

• Ongoing treatment with phenprocoumon or other cumarin derivates

• Thrombocytopenia (platelet count <100.000/µL) or leucopenia (white blood cell count < 2.000/µL)

• Gastrointestinal bleeding within the last 6 months prior to visit -2 or hemolysis

• Evidence of acute or chronic infection by a C-reactive protein value of > 30 mg/L

• Suspicion or known PRCA (pure red cell aplasia)

• Previously diagnosed HIV or acute hepatitis infection

• History of epilepsy or epileptic seizures or treatment for epilepsy within the past 6 months prior to screening

• Planned major surgery (with expected high blood loss) during the next 3 months or major surgery within the previous 3 months (except laser photocoagulation, access surgery)

• Clinical evidence of active malignant diseases within the last 5 years (except non-melanoma skin cancer)

• Pregnancy, breastfeeding women or women not using a highly effective birth control method (e.g. implants, injectables, combined oral contraceptives, IUD, sexual abstinence, vasectomised partner)

• Known history of severe drug related allergies (e.g. anaphylactic shock)

• Known allergy to one of the ingredients of the test product or hypersensitivity to mammalian-derived products

• Known or suspicion of any non-compliance with respect to subcutaneous treatment

• Simultaneous participation in another clinical study or participation in a study in the month preceding visit-2 or previously randomized in this study

• Participation in another ESA study in the 3 months preceding visit -2

• Any other condition which at the investigator's discretion may put the patient at risk or which may confound the study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Diakonissen KH Salzburg	Salzburg		Austria	5020
2	LKH Steyr	Steyr		Austria	4400
3	Krankenanstalt der Stadt Wien	Wien		Austria	1030
4	AKH Wien	Wien		Austria	1090
5	Sozialmedizinisches Zentrum Ost Donauspital	Wien		Austria	1220
6	MHAT Pazardijk	Pazardzhik		Bulgaria	4400
7	MHAT Sveti Ivan Rilski	Sofia		Bulgaria	1431
8	MHAT Stara Zagora	Stara Zagora		Bulgaria	6003
9	MHAT "Sv. Anna"	Varna		Bulgaria	9002
10	Ambulance vnitrního lékarstvi	Brno		Czechia	61500
11	Nemocnice Kladno	Kladno		Czechia	27259
12	Litomyslska nemocnice, a.s.	Litomyšl		Czechia	57014
13	Nemocnice s poliklinikou v Novem Jicine	Novi Jicin		Czechia	741 01
14	Dialcorp, s.r.o.	Praha 4 - Michle		Czechia	140 00
15	IKEM	Praha 4		Czechia	14021
16	FN Motol	Praha 5		Czechia	15006
17	Nemocnice Prostìjov	Prostìjov		Czechia	79604
18	Nemocnice Šternberk	Šternberk		Czechia	78501
19	Nefrologická a interní amb.	Žïár n. Sázavou		Czechia	591 01
20	CHU d'Amiens - Hopital Sud	Amiens		France	80054
21	CHU de Rouen - Hopital de Bois Guillaume	Bois-Guillaume		France	76230
22	Gesundheitszentrum Alzey	Alzey		Germany	55232
23	Studienzentrum Hämatologie / Onkologie / Diabetes	Aschaffenburg		Germany	63739
24	Gemeinschaftspraxis Dr. med. Gert-Peter Dragoun, Dr. med Günther Hevendehl	Aschaffenburg		Germany	63741
25	Nephrologische Praxis Bad Münder	Bad Münder		Germany	31848
26	Praxis Dr. Scharla	Bad Reichenhall		Germany	83435
27	Nephrologisches Zentrum an Stadtkrankenhaus	Bad Wildungen		Germany	34537
28	Dialyse-Centrum	Bad Windsheim		Germany	91438
29	KfH Kuratorium f. Dialyse und Nierentransplantation e.V.	Bergisch Gladbach		Germany	51465
30	Schwerpunktpraxis für Diabetologie und Nephrologie	Bernkastel-Kues		Germany	54470
31	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Bischofswerda		Germany	01877
32	Nephrologische Gemeinschaftspraxis Dr. Rensinghoff & Dr. Becker	Bochum-Wattenscheid		Germany	44866
33	Dialysepraxis drs. Riedasch/Schreiber	Coesfeld		Germany	48653
34	Praxis Dr. Kraatz	Demmin		Germany	17109
35	Gemeinschaftspraxis Dr. Steffen & Dr. Perino	Dinkelsbühl		Germany	91550
36	Diabetes- und Dialysezentrum Merker, Vogt	Dormagen		Germany	41539
37	Gemeinschaftspraxis Karlstraße	Düsseldorf		Germany	40210
38	Dialysepraxis Häger, Schanze, Brause	Düsseldorf		Germany	40211
39	KfH Kuratorium f. Dialyse und Nierentransplantation e.V.	Eberswalde		Germany	16225
40	Gemeinschaftspraxis Dr. Spitthöver, Dr. Knee, Dr. Gröschel	Essen		Germany	45127
41	Praxis Dr. Zimmermann	Essen		Germany	45136
42	Praxis Dr. Lüdemann	Falkensee		Germany	14612
43	Dialysepraxis	Friedrichroda		Germany	99894
44	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Fürstenzell		Germany	94081
45	Dialysepraxis Barmbek	Hamburg		Germany	22297
46	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Haßfurt		Germany	97437
47	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Heringen		Germany	36266
48	Dialysezentrum	Homberg/Efze		Germany	34576
49	Gemeinschaftspraxis und Dialyse	Hürth		Germany	50354
50	Dialyseplaxis DR. Rieck, DR. Göbel, DR. Wagner	Krefeld		Germany	47798
51	Leipziger Institut für Präventivmedizin	Leipzig		Germany	04103
52	Med Center Leipzig	Leipzig		Germany	04107
53	GDG Gemeinnützige Dialyse Gesellschaft	Leverkusen		Germany	51373
54	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Ludwigshafen		Germany	67059
55	Gemeinschaftspraxis Dres. Leistikow, Hafezi und Sandner	Mannheim		Germany	68309
56	Praxis Dr. Schütterle	Marburg		Germany	35043
57	Praxis Dr. Vogel-Wagner	Mittweida		Germany	09648
58	Praxis Dr. Rose, Pohlmeier und Dr. Lammers	Münster		Germany	48145
59	Dialyse Nettetal	Nettetal		Germany	41334
60	KfH Kuratorium für dialyse und Nierentransplantation e.V.	Nördlingen		Germany	86720
61	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Passau		Germany	94032
62	Praxis Dipl. med. Kosch	Pirna		Germany	01796
63	Dialysepraxis Dipl. med. Gierak & Dipl. med. Rettig	Quedlinburg		Germany	06484
64	Klinik für Nephrologie und Allgemeine Innere Medizin	Solingen		Germany	42653
65	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Straubing		Germany	94315
66	Gemeinschaftspraxis Dr. Kirchner und Dr. Menge	Sömmerda		Germany	99610
67	Praxis Dr. med. Mauersberger	Villingen-Schwenningen		Germany	78054
68	Kamineni Hospitals Ltd.	Hyderabaad		India	500068
69	NIZAM Institute of Medical Sciences	Hyderabaad		India	500082
70	Bombay Hospital	Indore		India	452010
71	Monilek Hospital and Research Center	Jaipur		India	302004
72	Vinaya Hospital & Research Centre	Mangalore		India	575003
73	Pulse Diagnostix Cardiac and Medical Center	Pune		India	411001
74	Kerala Institute of Medical Sciences	Trivandrum		India	695029
75	SP ZOZ Miejski Szpital Zespolony	Czestochowa		Poland	42200
76	Specjalistyczna Przychodnia Lekarska Medikard	Plock		Poland	09-402
77	Szpital Wojewódzki w Poznaniu	Poznan		Poland	60-479
78	Specjalistyczne Centrum Diagnostyczno-Lecznicze Bamberski Dwor (Solumed SC)	Poznan		Poland	60-539
79	NZOZ NEFROLUX Sp. J. Lucjan Sobieraj, Wojciech Kaminski	Siemianowice Slaskie		Poland	41100
80	Wojewodzki Szpital Specjalistyczny nr. 1 im. Jozefa Gasinskiego	Tychy		Poland	43-100
81	Szpital Praski p.w. Przemienienia Panskiego II Oddzia Chorob Wewnetrznych	Warszawa		Poland	03401
82	NZOZ Centrum Badan Klinicznych	Wroclaw		Poland	50-349
83	Centrul Medical de Diagnostic si Tratament Ambulator si Medicina Preventiva Bucuresti	Bucuresti		Romania	011794
84	Institutul National de DiabetNutritie si Boli Metabolice Paulescu	Bucuresti		Romania	020475
85	Institutul Clinic Fundeni	Bucuresti		Romania	022328
86	Spitalul Universitar Bucuresti	Bucuresti		Romania	050098
87	Spitalul Clinic Judetean Cluj	Cluj		Romania	400 006
88	County Hospital Deva	Deva		Romania	330084
89	Spitalul Clinic CI Parhon Iasi	Iasi		Romania	700503
90	Dr. Gavril Curteanu Clinical Hospital	Oradea		Romania	410469
91	County Hospital Tg Mures	Tg Mures		Romania	540103
92	SC Medicali's SRL	Timisoara		Romania	300359
93	Emergency Clinical County Hospital	Timisoara		Romania	300736
94	Spitalul Judetean Timisoara	Timisoara		Romania	300736
95	Policlinica Dr. Citu	Timisoara		Romania	300766
96	Municipal medical Institution "City Hospital #1"	Barnaul		Russian Federation	656099
97	Municipal Institution "City Clinical Hospital #40"	Ekaterinburg		Russian Federation	620102
98	State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"	Ekaterinburg		Russian Federation	620102
99	State Healthcare Institution "Kemerova Regional Clinical Hospital"	Kemerovo		Russian Federation	650066
100	Federal State Institution "National Medical Surgery center named after NI Pirogov of Federal Agency of Health Care and Social Development"	Moscow		Russian Federation	105203
101	State Educational Institution of Higher Professional Education "Moscow State University of Medicine and dentistry of Federal Agency of health Care and Social Development", City Clinical Hospital #23	Moscow		Russian Federation	109240
102	Russian University of Peoples Frienship (clinical base: City clinical hospital #53)	Moscow		Russian Federation	115432
103	State Health Care Institution City Clinical Hospital named after SP Botkin	Moscow		Russian Federation	125284
104	State healthcare Institution "Nizhegorodsky Regional Clinical Hospital named after NA Semashko"	Nizhniy Novgorod		Russian Federation	603126
105	State Healthcare Institution "Reoublic Hospital named after VA Baranov"	Petrozavodsk		Russian Federation	185019
106	Municipal healthcare Institution "City Clinical Hospital #2"	Pyatigorsk		Russian Federation	357538
107	State Healthcare Institution "Ryazan Regional Cardiological Dispensary"	Ryazan		Russian Federation	390026
108	State Educational Institution of High Professional Education Saratov State Medical University of Roszdrav	Saratov		Russian Federation	410053
109	State Educational Institution of Higher Professional Education "Smolensk State Medical Academy of Federal Agency of Health Care and Social Development"	Smolensk		Russian Federation	214018
110	State Educational Institution of Higher Professional Education "St. Petersburg State Medical Academy for Postgraduate studies of Roszdrav"	St. Petersburg		Russian Federation	191015
111	St. Petersburg State Healthcare Institution "City Mariinsky Hospital"	St. Petersburg		Russian Federation	191104
112	State Institution "St. petersburg Clinical research Institute of Emergency Medical Care named after I.I. Dzhanelidze"	St. petersburg		Russian Federation	192242
113	St. Petersburg State Healthcare Institution "City Outpatient Clinic #17"	St. petersburg		Russian Federation	194358
114	State Educational Institution of Higher Professional Education "St. Petersburg State Medical Academy named after I.I. Mechnikov of Roszdrav"	St. Petersburg		Russian Federation	195067
115	State Institute St. Petersburg	St. Petersburg		Russian Federation	195067
116	State Educational Institution of Higher Professional Education "St. Petersburg State Medical Institute named after IP Pavlov of Roszdrav"	St. Petersburg		Russian Federation	197022
117	State Institution Scientific Research Institute of Cardiology of Tomsk Research Center of Siberian Branch of Russian Academy of Medical Sciences	Tomsk		Russian Federation	634012
118	SibMedCenter LLC	Tomsk		Russian Federation	634041
119	Municipal Healthcare Institution "City Clinical Hospital #2"	Yaroslavl		Russian Federation	150010
120	State Healthcare Institution of Yaroslavl region "Regional Clinical Hosptal"	Yaroslavl		Russian Federation	150062
121	SMOLKO s.r.o.	Kosice		Slovakia	04001
122	MEDIKOL s.r.o.	Košice		Slovakia	040 01
123	FN Trnava	Trnava		Slovakia	917 75

Sponsors and Collaborators

• Sandoz

Investigators

• Study Chair: Andrea Vetter, Dr., Hexal AG

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT00701714
• Other Study ID Numbers: 2007-22-INJ-17
• First Posted: Jun 19, 2008
• Last Update Posted: Feb 5, 2018
• Last Verified: Jul 1, 2017

• Keywords provided by Sandoz: Treatment; associated; with CRI
• Additional relevant MeSH terms: Renal Insufficiency; Renal Insufficiency, Chronic; Anemia; Epoetin Alfa

Study Results

Participant Flow

Arm/Group Title	HX575, EPO HEXAL	ERYPO
Arm/Group Description	HX575 recombinant human erythropoietin alfa: Solution for injection (s.c.)	ERYPO: Solution for injection (s.c.)
Period Title: Treatment Period (up to 1 Year)
STARTED	174	163
COMPLETED	37	29
NOT COMPLETED	137	134
Period Title: Treatment Period (up to 1 Year)
STARTED	151	119
COMPLETED	144	112
NOT COMPLETED	7	7

Baseline Characteristics

Arm/Group Title	Treatmen HX575 EPO HEXAL	Treatment ERYPO	Total
Arm/Group Description	HX575 recombinant human erythropoietin alfa: Solution for injection (s.c.)	ERYPO: Solution for injection (s.c.)	Total of all reporting groups
Overall Participants	174	163	337
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (14.4)	64.9 (15)	64.5 (14.7)
Sex: Female, Male (Count of Participants)
Female	97 55.7%	98 60.1%	195 57.9%
Male	77 44.3%	65 39.9%	142 42.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	6 3.4%	7 4.3%	13 3.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	167 96%	155 95.1%	322 95.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 0.6%	1 0.6%	2 0.6%
Region of Enrollment (participants) [Number]
Austria	4 2.3%	1 0.6%	5 1.5%
Czech Republic	22 12.6%	19 11.7%	41 12.2%
Russian Federation	29 16.7%	24 14.7%	53 15.7%
Romania	47 27%	52 31.9%	99 29.4%
Poland	13 7.5%	14 8.6%	27 8%
Slovakia	4 2.3%	3 1.8%	7 2.1%
Bulgaria	4 2.3%	4 2.5%	8 2.4%
France	0 0%	1 0.6%	1 0.3%
Germany	45 25.9%	39 23.9%	84 24.9%
India	6 3.4%	6 3.7%	12 3.6%

Outcome Measures

1. Primary Outcome

Title	Change in Hemoglobin Level
Description	Mean absolute change in hemoglobin (baseline to end of study week 13)
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set required: "all randomized patients who received at least one dose of the study medication and for whom at least one Hb value after study day 27 was available". 3 out of 174 patients started in EPO HEXAL group and 6 out of 163 patients started in ERYPO group had no Hb values after study day 27 so they were excluded from analysis.

Arm/Group Title	HX575, EPO HEXAL	ERYPO
Arm/Group Description	HX575 recombinant human erythropoietin alfa: Solution for injection (s.c.)	ERYPO: Solution for injection (s.c.)
Measure Participants	171	157
Mean (Standard Deviation) [g/dL]	2.2 (1.0)	2.1 (1.2)

2. Primary Outcome

Title	Weekly Epoetin Dose
Description	Mean weekly epoetin dose [IU/kg] in study weeks 11-13
Time Frame	weeks 11-13

Outcome Measure Data

Analysis Population Description

Full analysis set required: "all randomized patients who received at least one dose of the study medication and for whom at least one Hb value after study day 27 was available". 3 out of 174 patients started in EPO HEXAL group and 6 out of 163 patients started in ERYPO group had no Hb values after study day 27 so they were excluded from analysis.

Arm/Group Title	HX575, EPO HEXAL	ERYPO
Arm/Group Description	HX575 recombinant human erythropoietin alfa: Solution for injection (s.c.)	ERYPO: Solution for injection (s.c.)
Measure Participants	171	157
Mean (Standard Deviation) [IU/kg]	55.1 (41.9)	57.9 (46.6)

3. Secondary Outcome

Title	Immunogenicity
Description	Number of participants with antibody formation against Epoetin during treatment period (safety set)
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatmen HX575 EPO HEXAL	Treatment ERYPO
Arm/Group Description	HX575 recombinant human erythropoietin alfa: Solution for injection (s.c.)	ERYPO: Solution for injection (s.c.)
Measure Participants	174	163
Number [participants]	5 2.9%	2 1.2%

Adverse Events

Time Frame	Treatment period: up to 1 year; Safety follow up period: 6 months
Adverse Event Reporting Description	Safety Population (SAF) was composed of all patients who received at least one dose of the study medication during treatment period
Arm/Group Title	Treatment HX575, EPO HEXAL		Treatment ERYPO		Safety Follow-up HX575, EPO HEXAL		Safety Follow-up ERYPO
Arm/Group Description	HX575 recombinant human erythropoietin alfa: Solution for injection (s.c.)		ERYPO: Solution for injection (s.c.)		Patients received HX575, EPO HEXAL during Treatment Period		Patients received ERYPO during Treatment Period
All Cause Mortality
	Treatment HX575, EPO HEXAL		Treatment ERYPO		Safety Follow-up HX575, EPO HEXAL		Safety Follow-up ERYPO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/174 (3.4%)		14/163 (8.6%)		2/151 (1.3%)		1/119 (0.8%)
Serious Adverse Events
	Treatment HX575, EPO HEXAL		Treatment ERYPO		Safety Follow-up HX575, EPO HEXAL		Safety Follow-up ERYPO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/174 (28.7%)		70/163 (42.9%)		22/151 (14.6%)		24/119 (20.2%)
Blood and lymphatic system disorders
Anaemia	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Aplasia pure red cell	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Haemorrhagic anaemia	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Cardiac disorders
Cardiac failure	4/174 (2.3%)	4	3/163 (1.8%)	3	0/151 (0%)	0	0/119 (0%)	0
Myocardial infarction	1/174 (0.6%)	1	2/163 (1.2%)	2	0/151 (0%)	0	1/119 (0.8%)	1
Angina pectoris	0/174 (0%)	0	2/163 (1.2%)	2	0/151 (0%)	0	0/119 (0%)	0
Atrial fibrillation	0/174 (0%)	0	2/163 (1.2%)	2	0/151 (0%)	0	1/119 (0.8%)	1
Coronary artery disease	2/174 (1.1%)	2	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Acute coronary syndrome	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Acute myocardial infarction	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Atrioventricular block complete	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Cardiac failure acute	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Cardiogenic shock	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Coronary artery insufficiency	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Myocardial ischaemia	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Sick sinus syndrome	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Sinus bradycardia	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Tachyarrhythmia	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Ventricular tachycardia	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Atrial flutter	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Cardiac arrest	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Coronary artery stenosis	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Eye disorders
Diabetic retinopathy	1/174 (0.6%)	1	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Vitreous haemorrhage	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Gastrointestinal disorders
Diarrhoea	2/174 (1.1%)	2	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Gastrointestinal haemorrhage	1/174 (0.6%)	1	2/163 (1.2%)	2	0/151 (0%)	0	0/119 (0%)	0
Ascites	1/174 (0.6%)	1	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Gastritis	1/174 (0.6%)	1	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Abdominal pain	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Diverticulum intestinal haemorrhagic	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Duodenitis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Dyspepsia	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Enteritis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Gastric ulcer	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Gastroduodenitis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Gastrointestinal perforation	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Haemorrhoidal haemorrhage	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Inguinal hernia	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Nausea	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Pancreatitis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Mesenteric occlusion	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
Peritonitis	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
General disorders
Oedema	2/174 (1.1%)	2	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Oedema peripheral	2/174 (1.1%)	2	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Chest pain	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
General physical health deterioration	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Generalised oedema	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Inflammation	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Hypertrophy	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Necrosis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Pyrexia	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Sudden death	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Hepatobiliary disorders
Cholestasis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Hepatic fibrosis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Portal vein thrombosis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Immune system disorders
Anaphylactic reaction	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Hypersensitivity	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Infections and infestations
Pneumonia	2/174 (1.1%)	2	4/163 (2.5%)	4	1/151 (0.7%)	1	0/119 (0%)	0
Bronchopneumonia	1/174 (0.6%)	1	1/163 (0.6%)	1	0/151 (0%)	0	1/119 (0.8%)	1
Lung infection	1/174 (0.6%)	1	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Appendiceal abscess	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Bacterial infection	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Bronchitis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Cellulitis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Febrile infection	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Gastroenteritis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Hepatitis C	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Injection site abscess	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Nasopharyngitis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Perianal abscess	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Pharyngitis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Pneumonia bacterial	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Respiratory tract infection viral	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Sialoadenitis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Tracheobronchitis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Urinary tract infection	1/174 (0.6%)	1	0/163 (0%)	0	1/151 (0.7%)	1	1/119 (0.8%)	1
Catheter sepsis	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Catheter site infection	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
Cytomegalovirus infection	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
Klebsiella sepsis	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
Sepsis	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
Injury, poisoning and procedural complications
Arteriovenous fistula site complication	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Arteriovenous fistula thrombosis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Concussion	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Contusion	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Femur fracture	0/174 (0%)	0	1/163 (0.6%)	1	1/151 (0.7%)	1	0/119 (0%)	0
Rib fracture	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Shunt thrombosis	1/174 (0.6%)	2	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Urinary bladder rupture	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Humerus fracture	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
Investigations
Anti-erythropoietin antibody positive	2/174 (1.1%)	2	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Blood creatine increased	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Blood creatinine increased	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Blood potassium increased	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	0/174 (0%)	0	4/163 (2.5%)	4	1/151 (0.7%)	1	0/119 (0%)	0
Dehydration	0/174 (0%)	0	3/163 (1.8%)	3	0/151 (0%)	0	0/119 (0%)	0
Diabetes mellitus inadequate control	3/174 (1.7%)	4	0/163 (0%)	0	2/151 (1.3%)	2	0/119 (0%)	0
Hyperkalaemia	1/174 (0.6%)	1	2/163 (1.2%)	2	0/151 (0%)	0	0/119 (0%)	0
Diabetes mellitus	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Hypervolaemia	1/174 (0.6%)	2	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Metabolic acidosis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Musculoskeletal and connective tissue disorders
Arthropathy	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Fistula	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Gouty arthritis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Osteoarthritis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Arthritis	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Intervertebral disc protrusion	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Spinal osteoarthritis	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/174 (0.6%)	1	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Benign breast neoplasm	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Colon cancer	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Hepatic neoplasm malignant	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Metastases to liver	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Metastases to lung	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Oesophageal carcinoma	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Rectal cancer	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Renal cancer stage II	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Bronchial carcinoma	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/174 (0.6%)	1	3/163 (1.8%)	3	1/151 (0.7%)	1	0/119 (0%)	0
Syncope	1/174 (0.6%)	1	2/163 (1.2%)	2	0/151 (0%)	0	0/119 (0%)	0
Transient ischaemic attack	1/174 (0.6%)	1	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Carotid sinus syndrome	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Coma	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Encephalopathy	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Haemorrhagic stroke	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Hypoglycaemic coma	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Hypotonia	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Haemorrhage intracranial	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Headache	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Thalamic infarction	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	2	0/119 (0%)	0
Renal and urinary disorders
Renal failure chronic	12/174 (6.9%)	13	22/163 (13.5%)	22	11/151 (7.3%)	11	10/119 (8.4%)	10
Renal failure	7/174 (4%)	7	6/163 (3.7%)	6	2/151 (1.3%)	2	2/119 (1.7%)	2
Renal impairment	2/174 (1.1%)	2	7/163 (4.3%)	7	1/151 (0.7%)	1	1/119 (0.8%)	1
Azotaemia	3/174 (1.7%)	3	3/163 (1.8%)	3	1/151 (0.7%)	1	1/119 (0.8%)	1
Anuria	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Diabetic nephropathy	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Glomerulonephritis chronic	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	1/119 (0.8%)	1
Nephrolithiasis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Nephrotic syndrome	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Renal disorder	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Renal tubular acidosis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Female genital tract fistula	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/174 (1.1%)	3	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Pleural effusion	1/174 (0.6%)	1	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Pulmonary oedema	0/174 (0%)	0	2/163 (1.2%)	2	0/151 (0%)	0	0/119 (0%)	0
Acute interstitial pneumonitis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Acute respiratory distress syndrome	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Chronic obstructive pulmonary disease	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Hypoventilation	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Pleurisy	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Pulmonary hypertension	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Respiratory failure	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Haemoptysis	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Surgical and medical procedures
Hip arthroplasty	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Arteriovenous fistula operation	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Vascular disorders
Hypertension	1/174 (0.6%)	1	1/163 (0.6%)	1	1/151 (0.7%)	1	1/119 (0.8%)	1
Hypertensive crisis	1/174 (0.6%)	1	1/163 (0.6%)	1	1/151 (0.7%)	1	0/119 (0%)	0
Arterial stenosis	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Circulatory collapse	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Deep vein thrombosis	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Dry gangrene	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	0/119 (0%)	0
Gangrene	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Peripheral arterial occlusive disease	0/174 (0%)	0	1/163 (0.6%)	1	0/151 (0%)	0	1/119 (0.8%)	1
Steal syndrome	1/174 (0.6%)	1	0/163 (0%)	0	0/151 (0%)	0	0/119 (0%)	0
Hypotension	0/174 (0%)	0	0/163 (0%)	0	1/151 (0.7%)	1	0/119 (0%)	0
Shock	0/174 (0%)	0	0/163 (0%)	0	0/151 (0%)	0	1/119 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Treatment HX575, EPO HEXAL		Treatment ERYPO		Safety Follow-up HX575, EPO HEXAL		Safety Follow-up ERYPO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	137/174 (78.7%)		132/163 (81%)		87/151 (57.6%)		58/119 (48.7%)
Blood and lymphatic system disorders
Anaemia	1/174 (0.6%)	1	1/163 (0.6%)	1	5/151 (3.3%)	5	2/119 (1.7%)	2
Cardiac disorders
Cardiac failure	5/174 (2.9%)	5	4/163 (2.5%)	4	0/151 (0%)	0	0/119 (0%)	0
Ventricular extrasystoles	2/174 (1.1%)	2	5/163 (3.1%)	6	1/151 (0.7%)	1	1/119 (0.8%)	1
Gastrointestinal disorders
Diarrhoea	7/174 (4%)	7	6/163 (3.7%)	7	4/151 (2.6%)	4	2/119 (1.7%)	2
Vomiting	3/174 (1.7%)	3	8/163 (4.9%)	9	0/151 (0%)	0	0/119 (0%)	0
Nausea	6/174 (3.4%)	6	4/163 (2.5%)	4	2/151 (1.3%)	2	0/119 (0%)	0
Abdominal pain upper	4/174 (2.3%)	6	5/163 (3.1%)	5	0/151 (0%)	0	1/119 (0.8%)	1
Gastritis	3/174 (1.7%)	3	5/163 (3.1%)	5	0/151 (0%)	0	1/119 (0.8%)	1
Constipation	1/174 (0.6%)	1	4/163 (2.5%)	4	1/151 (0.7%)	1	0/119 (0%)	0
General disorders
Oedema peripheral	21/174 (12.1%)	28	17/163 (10.4%)	22	4/151 (2.6%)	4	2/119 (1.7%)	2
Fatigue	10/174 (5.7%)	13	1/163 (0.6%)	1	3/151 (2%)	3	0/119 (0%)	0
Oedema	3/174 (1.7%)	3	5/163 (3.1%)	6	0/151 (0%)	0	0/119 (0%)	0
Pyrexia	2/174 (1.1%)	2	6/163 (3.7%)	6	2/151 (1.3%)	2	2/119 (1.7%)	2
Asthenia	2/174 (1.1%)	2	4/163 (2.5%)	4	2/151 (1.3%)	2	0/119 (0%)	0
Infections and infestations
Nasopharyngitis	17/174 (9.8%)	23	14/163 (8.6%)	17	5/151 (3.3%)	6	2/119 (1.7%)	2
Urinary tract infection	16/174 (9.2%)	21	12/163 (7.4%)	14	5/151 (3.3%)	5	6/119 (5%)	7
Bronchitis	8/174 (4.6%)	10	9/163 (5.5%)	10	3/151 (2%)	3	1/119 (0.8%)	1
Pneumonia	4/174 (2.3%)	5	4/163 (2.5%)	4	1/151 (0.7%)	1	0/119 (0%)	0
Upper respiratory tract infection	3/174 (1.7%)	4	5/163 (3.1%)	6	2/151 (1.3%)	2	0/119 (0%)	0
Investigations
Blood pressure increased	4/174 (2.3%)	4	4/163 (2.5%)	4	1/151 (0.7%)	1	1/119 (0.8%)	1
Anti-erythropoietin antibody positive	5/174 (2.9%)	7	2/163 (1.2%)	2	5/151 (3.3%)	5	2/119 (1.7%)	2
Gamma-glutamyltransferase increased	4/174 (2.3%)	4	0/163 (0%)	0	4/151 (2.6%)	4	2/119 (1.7%)	2
Metabolism and nutrition disorders
Hypoglycaemia	3/174 (1.7%)	4	11/163 (6.7%)	13	2/151 (1.3%)	2	0/119 (0%)	0
Anorexia	4/174 (2.3%)	6	3/163 (1.8%)	4	2/151 (1.3%)	2	0/119 (0%)	0
Hyperkalaemia	3/174 (1.7%)	3	4/163 (2.5%)	5	5/151 (3.3%)	6	2/119 (1.7%)	2
Musculoskeletal and connective tissue disorders
Back pain	4/174 (2.3%)	4	6/163 (3.7%)	6	1/151 (0.7%)	1	2/119 (1.7%)	3
Osteoarthritis	2/174 (1.1%)	2	4/163 (2.5%)	5	1/151 (0.7%)	1	0/119 (0%)	0
Pain in extremity	4/174 (2.3%)	4	1/163 (0.6%)	2	1/151 (0.7%)	1	0/119 (0%)	0
Nervous system disorders
Dizziness	7/174 (4%)	7	4/163 (2.5%)	4	1/151 (0.7%)	1	1/119 (0.8%)	1
Headache	7/174 (4%)	7	4/163 (2.5%)	5	0/151 (0%)	0	1/119 (0.8%)	1
Renal and urinary disorders
Renal failure chronic	13/174 (7.5%)	16	24/163 (14.7%)	24	13/151 (8.6%)	13	11/119 (9.2%)	13
Renal impairment	3/174 (1.7%)	3	9/163 (5.5%)	9	1/151 (0.7%)	1	2/119 (1.7%)	2
Renal failure	7/174 (4%)	7	6/163 (3.7%)	6	3/151 (2%)	3	2/119 (1.7%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/174 (2.3%)	4	4/163 (2.5%)	4	0/151 (0%)	0	1/119 (0.8%)	1
Epistaxis	4/174 (2.3%)	4	4/163 (2.5%)	4	2/151 (1.3%)	2	1/119 (0.8%)	1
Skin and subcutaneous tissue disorders
Pruritus	5/174 (2.9%)	5	2/163 (1.2%)	2	1/151 (0.7%)	1	0/119 (0%)	0
Vascular disorders
Hypertension	38/174 (21.8%)	73	41/163 (25.2%)	88	10/151 (6.6%)	14	10/119 (8.4%)	11
Hypotension	4/174 (2.3%)	4	6/163 (3.7%)	7	2/151 (1.3%)	2	0/119 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor shall have the right to the first publication or presentation of the results of the study which is intended to be a joint, multi-center publication of the study results. Following the first publication, institutions and/or Principal Investigators may publish or present data or results from the study per the terms of the clinical trial agreement.