ACCESS: Study to Compare Safety and Efficacy of HX575 Epoetin Alfa and US-licensed Epoetin Alfa

• Sponsor: Sandoz (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01693029
• Collaborator: (none)
• Enrollment: 435
• Locations: 52
• Arms: 2
• Duration (Months): 29.9
• Patients Per Site: 8.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to show biosimilarity of HX575 epoetin alfa with the US licensed reference product Epogen®/Procrit® when applied subcutaneously. This study is intended to generate data supporting that the efficacy and safety under treatment with HX575 and Epogen®/Procrit® are comparable.

Condition or Disease	Intervention/Treatment	Phase
Anemia; Chronic Kidney Disease (CKD)	Drug: HX575 epoetin alfa; Drug: US-licensed epoetin alfa	Phase 3

Detailed Description

This is a randomized, double-blind, parallel-group, multicenter study to evaluate the efficacy and safety of HX575 epoetin alfa vs. US-licensed epoetin alfa (Epogen®/Procrit®) in the treatment of anemia associated with chronic kidney disease (CKD).

Study Design

• Study Type: Interventional
• Actual Enrollment: 435 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of HX575 Epoetin Alfa vs. US Licensed Epoetin Alfa (Epogen®/Procrit®) in the Treatment of Anemia Associated With Chronic Kidney Disease
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HX575 epoetin alfa HX575, recombinant human epoetin alfa	Drug: HX575 epoetin alfa; Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.; Other Names: Binocrit® (Europe) Epoetin alfa HEXAL® (Europe) Abseamed® (Europe)
Active Comparator: US-licensed epoetin alfa US-licensed recombinant human epoetin alfa	Drug: US-licensed epoetin alfa; Solution for subcutaneous injection.; Other Names: Epogen® Procrit®

Outcome Measures

Primary Outcome Measures

1. Mean Absolute Change in Hemoglobin Levels Between the Screening/Baseline Period (Week -4 to Day 1) and the Evaluation Period (Week 21-28) [Week -4 to Day1 and Week 21-28]

   Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study .

2. Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28) [Week -4 to Day1 and Week 21-28]

   Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study .

Secondary Outcome Measures

1. Mean Weekly Dose During Evaluation Period (Week 21-28) [Week 21-28]

   Mean weekly study drug dose during evaluation period (Week 21-28)

2. Incidence of Antibody Formation Against Epoetin [52 weeks]

   Number of patients with positive antidrug antibody (ADA) finding at any time during their treatment period. Count includes 2 patients (1 in each arm) that already had a positive ADA Baseline finding. ADA testing performed by by Radio-Immuno-Precipitation assay. No patient developed neutralizing antibodies.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with end stage renal disease (stage CKD 5d), receiving stable subcutaneous maintenance therapy with Epogen® or Procrit® at least once per week

• Mean hemoglobin level between 9.0 - 11.5 g/dL during the screening period

• Adequate iron substitution

Exclusion Criteria:

• Contraindications for Erythropoiesis Stimulating Agent (ESA) therapy

• History of Pure Red Cell Aplasia (PRCA), or anti-erythropoietin (EPO) antibodies

• Known Human Immunodeficiency Virus (HIV) or Hepatitis B infection

• Hepatitis C infection on an active treatment

• Symptomatic congestive heart failure (New York Heart Association [NYHA] class III and IV)

• Unstable angina pectoris, or cardiac infarction during the last 6 months prior to randomization

• Percutaneous coronary intervention, or coronary artery bypass grafting during the last 6 months prior to randomization

• History of malignancy of any organ system

• Systemic lupus erythematous

• Immunocompromized patients

Other In-/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southwestern Kidney Institute	Tempe	Arizona	United States	85284
2	North America Research Institute	Azusa	California	United States	91702
3	Pegasus Dialysis, LLC	Bakersfield	California	United States	93308
4	Central Nephrology Medical Group	Bakersfield	California	United States	93309
5	California Institute of Renal Research	Chula Vista	California	United States	91910
6	Renal Consultants Medical Group	Granada Hills	California	United States	91344
7	Angel Kidney Care of Inglewood Dialysis Center	Inglewood	California	United States	90301
8	California Institute of Renal Research	La Mesa	California	United States	91942
9	Alliance Research Centers	Laguna Hills	California	United States	92653
10	Academic Medical Research Institute	Los Angeles	California	United States	90022
11	Ronald Reagan Medical Center, Department of Pharmaceutical Services, Drug Information Center	Los Angeles	California	United States	90025
12	Tower Nephrology Medical Group	Los Angeles	California	United States	90048
13	St Vincent Dialysis Center	Los Angeles	California	United States	90057
14	Kidney Research Center	Lynwood	California	United States	90262
15	Valley Renal Medical Group	Northridge	California	United States	91324
16	Ontario Dialysis, Inc.	Ontario	California	United States	91762
17	Apex Research of Riverside	Riverside	California	United States	92505
18	Capital Nephrology Medical Group	Sacramento	California	United States	95825
19	California Institute of Renal Research	San Diego	California	United States	92111
20	La Jolla Clinical Research, Inc.	San Diego	California	United States	92154
21	North America Research Institute	San Dimas	California	United States	91773
22	American Institute of Research	Whittier	California	United States	90603
23	South Florida Nephrology	Coral Springs	Florida	United States	33071
24	Pines Clinical Research Inc.	Hollywood	Florida	United States	33020
25	Genesis Clinical Research Corporation	Tampa	Florida	United States	33614
26	Atekha Nephrology Clinic LLC	Statesboro	Georgia	United States	30458
27	Four Rivers Clinical Research, Incorporated	Paducah	Kentucky	United States	42003
28	Northwest Louisana Nephrology	Shreveport	Louisiana	United States	71101
29	Germantown Dialysis	Germantown	Maryland	United States	20874
30	Fresenius Management Services, Inc.	Farmington	Missouri	United States	63640
31	Creighton University	Omaha	Nebraska	United States	68131
32	Kidney Specialists of Southern Nevada	Las Vegas	Nevada	United States	89106
33	Seacoast Kidney and Hypertension Specialist, PLLC	Portsmouth	New Hampshire	United States	03801
34	Renal Medicine Associates	Albuquerque	New Mexico	United States	87109
35	New York Hospital Queens	Fresh Meadows	New York	United States	11365
36	Metrolina Nephrology Associates, PA	Charlotte	North Carolina	United States	28207
37	Boice-Willis Clinic, PA	Rocky Mount	North Carolina	United States	27804
38	Southeastern Dialysis Center	Wilmington	North Carolina	United States	28401
39	Northeast Clinical Research Centers, Inc.	Bethlehem	Pennsylvania	United States	18017
40	Delaware Valley Nephrology and Hypertension Associates, PC	Philadelphia	Pennsylvania	United States	19118
41	Rhode Island Hospital	Providence	Rhode Island	United States	02903
42	Palmetto Nephrology PA	Orangeburg	South Carolina	United States	29118
43	SC Nephrology & Hypertension Center, Inc.	Orangeburg	South Carolina	United States	29118
44	Knoxville Kidney Center PLLC	Knoxville	Tennessee	United States	37923
45	Research Management, Inc.	Austin	Texas	United States	78756
46	Gamma Clinical Research Institute	Edinburg	Texas	United States	78539
47	Nephrology, P.A.	Houston	Texas	United States	77030
48	Clinical Trial Network	Houston	Texas	United States	77074
49	Renal Associates, PA	San Antonio	Texas	United States	78215-2035
50	Southern Utah Kidney and Hypertension Center	Saint George	Utah	United States	84770
51	Mendez Center For Clinical Research, LLC	Alexandria	Virginia	United States	22304
52	West Virginia University Hospitals and Clinic	Morgantown	West Virginia	United States	26506

Sponsors and Collaborators

• Sandoz

Investigators

• Study Director: Sandoz Biopharmaceutical Clinical Development, Sandoz Biopharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT01693029
• Other Study ID Numbers: HX575-307
• First Posted: Sep 26, 2012
• Last Update Posted: Jul 2, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Sandoz: erythropoietin alfa; CKD 5d
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Epoetin Alfa

Study Results

Participant Flow

Arm/Group Title	HX575 Epoetin Alfa	US-licensed Epoetin Alfa
Arm/Group Description	HX575, recombinant human epoetin alfa HX575 epoetin alfa: Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.	US-licensed recombinant human epoetin alfa US-licensed epoetin alfa: Solution for subcutaneous injection.
Period Title: Overall Study
STARTED	217	218
COMPLETED	173	161
NOT COMPLETED	44	57

Baseline Characteristics

Arm/Group Title	HX575 Epoetin Alfa	US-licensed Epoetin Alfa	Total
Arm/Group Description	HX575, recombinant human epoetin alfa HX575 epoetin alfa: Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.	US-licensed recombinant human epoetin alfa US-licensed epoetin alfa: Solution for subcutaneous injection.	Total of all reporting groups
Overall Participants	217	218	435
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.8 (13.76)	57.6 (13.40)	58.7 (13.61)
Sex: Female, Male (Count of Participants)
Female	82 37.8%	103 47.2%	185 42.5%
Male	135 62.2%	115 52.8%	250 57.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	95 43.8%	93 42.7%	188 43.2%
Not Hispanic or Latino	122 56.2%	125 57.3%	247 56.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	11 5.1%	5 2.3%	16 3.7%
Asian	6 2.8%	13 6%	19 4.4%
Native Hawaiian or Other Pacific Islander	4 1.8%	0 0%	4 0.9%
Black or African American	57 26.3%	72 33%	129 29.7%
White	139 64.1%	128 58.7%	267 61.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	217 100%	218 100%	435 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	167.2 (10.17)	166.0 (10.33)	166.6 (10.26)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	82.8 (20.75)	86.5 (24.32)	84.6 (22.66)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.55 (6.872)	31.41 (8.783)	30.48 (7.933)
Primary cause of Chronic Kidney Disease (CKD) (Count of Participants)
Diabetes mellitus	115 53%	122 56%	237 54.5%
Hypertension	65 30%	52 23.9%	117 26.9%
Chronic glomerulonephritis	13 6%	16 7.3%	29 6.7%
Kidney abnormalities	8 3.7%	11 5%	19 4.4%
Polycystic kidney disease	5 2.3%	4 1.8%	9 2.1%
Urinary tract obstruction	2 0.9%	0 0%	2 0.5%
Vasculitis	2 0.9%	0 0%	2 0.5%
Amyloidosis	1 0.5%	0 0%	1 0.2%
Unknown	3 1.4%	9 4.1%	12 2.8%
Other	3 1.4%	4 1.8%	7 1.6%
Type of last Erythropoiesis Stimulating Agent (ESA) therapy prior (Count of Participants)
Epogen	217 100%	215 98.6%	432 99.3%
Procrit	0 0%	3 1.4%	3 0.7%
Time since start of ESA therapy (months) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [months]	30.59	36.24	32.95
Time since start of dialysis (months) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [months]	36.11	41.08	38.60
Method of dialysis at Baseline (Count of Participants)
Hemodialysis	192 88.5%	192 88.1%	384 88.3%
Peritoneal dialysis	25 11.5%	26 11.9%	51 11.7%

Outcome Measures

1. Primary Outcome

Title	Mean Absolute Change in Hemoglobin Levels Between the Screening/Baseline Period (Week -4 to Day 1) and the Evaluation Period (Week 21-28)
Description	Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study .
Time Frame	Week -4 to Day1 and Week 21-28

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consists of all randomized patients who were exposed to treatment with study drug for at least four weeks and have at least one Hb value available at week 4 or later. Following the intent-to-treat principle, patients are analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	HX575 Epoetin Alfa	US-licensed Epoetin Alfa
Arm/Group Description	HX575, recombinant human epoetin alfa HX575 epoetin alfa: Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.	US-licensed recombinant human epoetin alfa US-licensed epoetin alfa: Solution for subcutaneous injection.
Measure Participants	210	212
Least Squares Mean (Standard Error) [g/dL]	-0.0960 (0.0575)	-0.0035 (0.0573)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HX575 Epoetin Alfa, US-licensed Epoetin Alfa
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin (-0.5, 0.5) g/dL. Results from ANCOVA with factors "treatment group" and covariates mean baseline Hb and mean weekly dose during the evaluation period (Week 21-28)
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0926
	Confidence Interval	(2-Sided) 90%; -0.2264 to 0.0413
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		95% confidence interval for the difference is (-0.2522, 0.0670).

2. Primary Outcome

Title	Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28)
Description	Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study .
Time Frame	Week -4 to Day1 and Week 21-28

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consists of all randomized patients who were exposed to treatment with study drug for at least four weeks and have at least one Hb value available at week 4 or later. Following the intent-to-treat principle, patients are analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	HX575 Epoetin Alfa	US-licensed Epoetin Alfa
Arm/Group Description	HX575, recombinant human epoetin alfa HX575 epoetin alfa: Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.	US-licensed recombinant human epoetin alfa US-licensed epoetin alfa: Solution for subcutaneous injection.
Measure Participants	210	212
Baseline period	10.53 (0.635)	10.50 (0.615)
Evaluation period	10.42 (0.826)	10.51 (0.873)
Change from baseline period to evaluation period	-0.11 (1.011)	0.01 (0.953)

3. Secondary Outcome

Title	Mean Weekly Dose During Evaluation Period (Week 21-28)
Description	Mean weekly study drug dose during evaluation period (Week 21-28)
Time Frame	Week 21-28

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consists of all randomized patients who were exposed to treatment with study drug for at least four weeks and have at least one Hb value available at week 4 or later. Following the intent-to-treat principle, patients are analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	HX575 Epoetin Alfa	US-licensed Epoetin Alfa
Arm/Group Description	HX575, recombinant human epoetin alfa HX575 epoetin alfa: Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.	US-licensed recombinant human epoetin alfa US-licensed epoetin alfa: Solution for subcutaneous injection.
Measure Participants	210	212
Mean (Standard Deviation) [international units]	5876.5 (5785.50)	5804.0 (6343.70)

4. Secondary Outcome

Title	Incidence of Antibody Formation Against Epoetin
Description	Number of patients with positive antidrug antibody (ADA) finding at any time during their treatment period. Count includes 2 patients (1 in each arm) that already had a positive ADA Baseline finding. ADA testing performed by by Radio-Immuno-Precipitation assay. No patient developed neutralizing antibodies.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All patients treated with study drug with a post-baseline antibody assessment

Arm/Group Title	HX575 Epoetin Alfa	US-licensed Epoetin Alfa
Arm/Group Description	HX575, recombinant human epoetin alfa HX575 epoetin alfa: Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.	US-licensed recombinant human epoetin alfa US-licensed epoetin alfa: Solution for subcutaneous injection.
Measure Participants	214	216
Count of Participants [Participants]	7 3.2%	2 0.9%

Adverse Events

Time Frame	Adverse events were collected from the date of informed consent until the end of the treatment period, for approximately 1 year.
Adverse Event Reporting Description	Adverse events recorded before first study drug were considered pre-treatment adverse events, adverse events recorded more than 30 days after last study drug treatment were considered post-treatment emergent adverse event. Only treatment-emergent adverse events are shown in adverse events counts.
Arm/Group Title	HX575 Epoetin Alfa		US-licensed Epoetin Alfa
Arm/Group Description	HX575, recombinant human epoetin alfa HX575 epoetin alfa: Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.		US-licensed recombinant human epoetin alfa US-licensed epoetin alfa: Solution for subcutaneous injection.
All Cause Mortality
	HX575 Epoetin Alfa		US-licensed Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/217 (2.3%)		11/218 (5%)
Serious Adverse Events
	HX575 Epoetin Alfa		US-licensed Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/217 (41.9%)		90/218 (41.3%)
Blood and lymphatic system disorders
Anaemia	4/217 (1.8%)	4	6/218 (2.8%)	6
Leukocytosis	0/217 (0%)		2/218 (0.9%)	2
Pancytopenia	1/217 (0.5%)	1	0/218 (0%)	1
Cardiac disorders
Cardiac failure congestive	8/217 (3.7%)	9	4/218 (1.8%)	5
Atrial fibrillation	3/217 (1.4%)	4	7/218 (3.2%)	8
Cardiac arrest	4/217 (1.8%)	4	3/218 (1.4%)	4
Acute myocardial infarction	5/217 (2.3%)	5	2/218 (0.9%)	2
Coronary artery disease	5/217 (2.3%)	5	2/218 (0.9%)	2
Angina pectoris	1/217 (0.5%)	1	3/218 (1.4%)	3
Acute coronary syndrome	1/217 (0.5%)	2	2/218 (0.9%)	2
Cardio-respiratory arrest	2/217 (0.9%)	2	1/218 (0.5%)	1
Ventricular tachycardia	0/217 (0%)		3/218 (1.4%)	3
Cardiogenic shock	1/217 (0.5%)	1	1/218 (0.5%)	1
Cardiac disorder	1/217 (0.5%)	1	0/218 (0%)	1
Myocardial infarction	1/217 (0.5%)	1	0/218 (0%)	1
Palpitations	1/217 (0.5%)	1	0/218 (0%)	1
Cardiovascular deconditioning	0/217 (0%)		1/218 (0.5%)	1
Tachycardia	0/217 (0%)		1/218 (0.5%)	1
Ventricular fibrillation	0/217 (0%)		1/218 (0.5%)	1
Ear and labyrinth disorders
Deafness	1/217 (0.5%)	1	0/218 (0%)	1
Endocrine disorders
Hyperparathyroidism	1/217 (0.5%)	1	1/218 (0.5%)	1
Gastrointestinal disorders
Gastritis	3/217 (1.4%)	3	1/218 (0.5%)	1
Abdominal pain	1/217 (0.5%)	1	3/218 (1.4%)	3
Gastrointestinal haemorrhage	0/217 (0%)		4/218 (1.8%)	4
Diabetic gastroparesis	0/217 (0%)		2/218 (0.9%)	4
Impaired gastric emptying	1/217 (0.5%)	1	1/218 (0.5%)	2
Nausea	1/217 (0.5%)	1	1/218 (0.5%)	1
Vomiting	1/217 (0.5%)	1	1/218 (0.5%)	1
Haematochezia	0/217 (0%)		2/218 (0.9%)	2
Pancreatitis	0/217 (0%)		2/218 (0.9%)	2
Upper gastrointestinal haemorrhage	0/217 (0%)		2/218 (0.9%)	2
Colitis	0/217 (0%)		1/218 (0.5%)	2
Oesophagitis	0/217 (0%)		1/218 (0.5%)	2
Abdominal hernia	1/217 (0.5%)	1	0/218 (0%)	1
Diarrhoea	1/217 (0.5%)	1	0/218 (0%)	1
Dyspepsia	1/217 (0.5%)	1	0/218 (0%)	1
Erosive oesophagitis	1/217 (0.5%)	1	0/218 (0%)	1
Inguinal hernia	1/217 (0.5%)	1	0/218 (0%)	1
Large intestinal ulcer haemorrhage	1/217 (0.5%)	1	0/218 (0%)	1
Large intestine polyp	1/217 (0.5%)	1	0/218 (0%)	1
Rectal haemorrhage	1/217 (0.5%)	1	0/218 (0%)	1
Abdominal pain upper	0/217 (0%)		1/218 (0.5%)	1
Duodenitis	0/217 (0%)		1/218 (0.5%)	1
Gastric ulcer	0/217 (0%)		1/218 (0.5%)	1
Gastritis erosive	0/217 (0%)		1/218 (0.5%)	1
Gastrointestinal disorder	0/217 (0%)		1/218 (0.5%)	1
Gastrooesophageal reflux disease	0/217 (0%)		1/218 (0.5%)	1
Haematemesis	0/217 (0%)		1/218 (0.5%)	1
Haemorrhoidal haemorrhage	0/217 (0%)		1/218 (0.5%)	1
Large intestine perforation	0/217 (0%)		1/218 (0.5%)	1
Peptic ulcer	0/217 (0%)		1/218 (0.5%)	1
Umbilical hernia	0/217 (0%)		1/218 (0.5%)	1
General disorders
Non-cardiac chest pain	6/217 (2.8%)	7	2/218 (0.9%)	2
Medical device complication	2/217 (0.9%)	2	2/218 (0.9%)	2
Pyrexia	3/217 (1.4%)	3	0/218 (0%)	3
Asthenia	0/217 (0%)		3/218 (1.4%)	3
Device malfunction	1/217 (0.5%)	1	1/218 (0.5%)	1
Systemic inflammatory response syndrome	0/217 (0%)		2/218 (0.9%)	2
Catheter site pain	0/217 (0%)		1/218 (0.5%)	2
Necrosis	1/217 (0.5%)	1	0/218 (0%)	1
Pain	1/217 (0.5%)	1	0/218 (0%)	1
Chest discomfort	0/217 (0%)		1/218 (0.5%)	1
Hepatobiliary disorders
Hepatitis acute	1/217 (0.5%)	1	0/218 (0%)	1
Cholecystitis acute	0/217 (0%)		1/218 (0.5%)	1
Cholelithiasis	0/217 (0%)		1/218 (0.5%)	1
Infections and infestations
Pneumonia	9/217 (4.1%)	9	10/218 (4.6%)	12
Cellulitis	7/217 (3.2%)	8	7/218 (3.2%)	7
Peritonitis	5/217 (2.3%)	6	3/218 (1.4%)	3
Gangrene	3/217 (1.4%)	3	4/218 (1.8%)	7
Sepsis	1/217 (0.5%)	1	4/218 (1.8%)	4
Staphylococcal bacteraemia	5/217 (2.3%)		5/218 (2.3%)	5
Septic shock	3/217 (1.4%)	3	1/218 (0.5%)	1
Urinary tract infection	1/217 (0.5%)	1	3/218 (1.4%)	3
Bacteraemia	2/217 (0.9%)	2	1/218 (0.5%)	1
Gastroenteritis viral	2/217 (0.9%)	2	1/218 (0.5%)	1
Osteomyelitis	2/217 (0.9%)	2	1/218 (0.5%)	1
Arteriovenous fistula site infection	1/217 (0.5%)	1	2/218 (0.9%)	2
Bronchitis	0/217 (0%)		2/218 (0.9%)	3
Streptococcal bacteraemia	2/217 (0.9%)	2	0/218 (0%)	2
Cystitis	1/217 (0.5%)	1	1/218 (0.5%)	1
Subcutaneous abscess	1/217 (0.5%)	1	1/218 (0.5%)	1
Lobar pneumonia	0/217 (0%)		2/218 (0.9%)	2
Arteriovenous graft site infection	0/217 (0%)		1/218 (0.5%)	2
Abscess neck	1/217 (0.5%)	1	0/218 (0%)	1
Diverticulitis	1/217 (0.5%)	1	0/218 (0%)	1
Intervertebral discitis	1/217 (0.5%)	1	0/218 (0%)	1
Staphylococcal infection	1/217 (0.5%)	1	0/218 (0%)	1
Urosepsis	1/217 (0.5%)	1	0/218 (0%)	1
Abdominal abscess	0/217 (0%)		1/218 (0.5%)	1
Catheter site infection	0/217 (0%)		1/218 (0.5%)	1
Device related sepsis	0/217 (0%)		1/218 (0.5%)	1
Endocarditis	0/217 (0%)		1/218 (0.5%)	1
Gastroenteritis	0/217 (0%)		1/218 (0.5%)	1
Influenza	0/217 (0%)		1/218 (0.5%)	1
Salmonellosis	0/217 (0%)		1/218 (0.5%)	1
Urinary tract infection enterococcal	0/217 (0%)		1/218 (0.5%)	1
Viral infection	0/217 (0%)		1/218 (0.5%)	1
Injury, poisoning and procedural complications
Arteriovenous fistula site haemorrhage	0/217 (0%)		4/218 (1.8%)	5
Arteriovenous fistula thrombosis	2/217 (0.9%)	3	1/218 (0.5%)	1
Arteriovenous fistula site complication	1/217 (0.5%)	1	1/218 (0.5%)	1
Humerus fracture	1/217 (0.5%)	1	1/218 (0.5%)	1
Laceration	1/217 (0.5%)	1	1/218 (0.5%)	1
Fall	1/217 (0.5%)	1	0/218 (0%)	1
Femur fracture	1/217 (0.5%)	1	0/218 (0%)	1
Foot fracture	1/217 (0.5%)	1	0/218 (0%)	1
Pelvic fracture	1/217 (0.5%)	1	0/218 (0%)	1
Procedural complication	1/217 (0.5%)	1	0/218 (0%)	1
Skin injury	1/217 (0.5%)	1	0/218 (0%)	1
Subdural haematoma	1/217 (0.5%)	1	0/218 (0%)	1
Tibia fracture	1/217 (0.5%)	1	0/218 (0%)	1
Ulna fracture	1/217 (0.5%)	1	0/218 (0%)	1
Arteriovenous graft aneurysm	0/217 (0%)		1/218 (0.5%)	1
Incision site erythema	0/217 (0%)		1/218 (0.5%)	1
Procedural hypotension	0/217 (0%)		1/218 (0.5%)	1
Pubis fracture	0/217 (0%)		1/218 (0.5%)	1
Toxicity to various agents	0/217 (0%)		1/218 (0.5%)	1
Chest pain	1/217 (0.5%)	1	0/218 (0%)	1
Investigations
Troponin increased	0/217 (0%)		1/218 (0.5%)	1
Metabolism and nutrition disorders
Hyperkalaemia	8/217 (3.7%)	9	7/218 (3.2%)	8
Fluid overload	6/217 (2.8%)	6	8/218 (3.7%)	13
Hypoglycaemia	3/217 (1.4%)	3	7/218 (3.2%)	7
Hypocalcaemia	1/217 (0.5%)	1	1/218 (0.5%)	1
Hypovolaemia	1/217 (0.5%)	1	1/218 (0.5%)	1
Hypercalcaemia	1/217 (0.5%)	1	0/218 (0%)	1
Hyperglycaemia	1/217 (0.5%)	1	0/218 (0%)	1
Cachexia	0/217 (0%)		1/218 (0.5%)	1
Lactic acidosis	0/217 (0%)		1/218 (0.5%)	1
Metabolic acidosis	0/217 (0%)		1/218 (0.5%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	2/217 (0.9%)	2	1/218 (0.5%)	1
Osteoarthritis	1/217 (0.5%)	1	0/218 (0%)	1
Back pain	0/217 (0%)		1/218 (0.5%)	1
Fistula	0/217 (0%)		1/218 (0.5%)	1
Muscle spasms	0/217 (0%)		1/218 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	0/217 (0%)		2/218 (0.9%)	2
Endometrial cancer	1/217 (0.5%)	1	0/218 (0%)	1
Bladder cancer	0/217 (0%)		1/218 (0.5%)	1
Lung neoplasm malignant	0/217 (0%)		1/218 (0.5%)	1
Nervous system disorders
Cerebrovascular accident	2/217 (0.9%)	2	2/218 (0.9%)	2
Syncope	2/217 (0.9%)	2	2/218 (0.9%)	2
Dizziness	2/217 (0.9%)	2	0/218 (0%)	2
Encephalopathy	1/217 (0.5%)	1	0/218 (0%)	1
Ischaemic stroke	1/217 (0.5%)	1	0/218 (0%)	1
Myoclonus	1/217 (0.5%)	1	0/218 (0%)	1
Lacunar infarction	0/217 (0%)		1/218 (0.5%)	1
Metabolic encephalopathy	0/217 (0%)		1/218 (0.5%)	1
Neuropathy peripheral	0/217 (0%)		1/218 (0.5%)	1
Presyncope	0/217 (0%)		1/218 (0.5%)	1
Speech disorder	0/217 (0%)		1/218 (0.5%)	1
Psychiatric disorders
Mental status changes	1/217 (0.5%)	1	4/218 (1.8%)	4
Suicidal ideation	1/217 (0.5%)	1	1/218 (0.5%)	1
Delirium	0/217 (0%)		1/218 (0.5%)	1
Renal and urinary disorders
Renal failure chronic	2/217 (0.9%)	2	2/218 (0.9%)	2
Haematuria	1/217 (0.5%)	1	0/218 (0%)	1
Renal mass	1/217 (0.5%)	1	0/218 (0%)	1
Urinary retention	1/217 (0.5%)	1	0/218 (0%)	1
Azotaemia	0/217 (0%)		1/218 (0.5%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/217 (0.5%)	1	0/218 (0%)	1
Postmenopausal haemorrhage	1/217 (0.5%)	1	0/218 (0%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	3/217 (1.4%)	3	2/218 (0.9%)	3
Pleural effusion	3/217 (1.4%)	3	2/218 (0.9%)	2
Acute respiratory failure	3/217 (1.4%)	3	1/218 (0.5%)	1
Dyspnoea	1/217 (0.5%)	1	1/218 (0.5%)	1
Epistaxis	1/217 (0.5%)	1	1/218 (0.5%)	1
Respiratory failure	1/217 (0.5%)	1	1/218 (0.5%)	1
Hypoxia	0/217 (0%)		2/218 (0.9%)	2
Asthma	1/217 (0.5%)	1	0/218 (0%)	1
Pneumonitis	1/217 (0.5%)	1	0/218 (0%)	1
Pulmonary oedema	1/217 (0.5%)	1	0/218 (0%)	1
Lung infiltration	0/217 (0%)		1/218 (0.5%)	1
Skin and subcutaneous tissue disorders
Skin ulcer	2/217 (0.9%)	2	1/218 (0.5%)	1
Diabetic foot	2/217 (0.9%)	2	0/218 (0%)	2
Dry gangrene	0/217 (0%)		1/218 (0.5%)	1
Social circumstances
Treatment noncompliance	0/217 (0%)		1/218 (0.5%)	1
Surgical and medical procedures
Biliary tract dilation procedure	1/217 (0.5%)	1	0/218 (0%)	1
Vascular disorders
Hypotension	2/217 (0.9%)	2	4/218 (1.8%)	5
Hypertension	1/217 (0.5%)	1	3/218 (1.4%)	3
Peripheral vascular disorder	2/217 (0.9%)	2	1/218 (0.5%)	1
Hypertensive crisis	1/217 (0.5%)	1	2/218 (0.9%)	2
Extremity necrosis	1/217 (0.5%)	1	1/218 (0.5%)	1
Aortic stenosis	0/217 (0%)		2/218 (0.9%)	2
Malignant hypertension	1/217 (0.5%)	1	0/218 (0%)	1
Orthostatic hypotension	1/217 (0.5%)	1	0/218 (0%)	1
Peripheral ischaemia	1/217 (0.5%)	1	0/218 (0%)	1
Accelerated hypertension	0/217 (0%)		1/218 (0.5%)	1
Lymphoedema	0/217 (0%)		1/218 (0.5%)	1
Other (Not Including Serious) Adverse Events
	HX575 Epoetin Alfa		US-licensed Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/217 (51.6%)		123/218 (56.4%)
Gastrointestinal disorders
Diarrhoea	21/217 (9.7%)	26	19/218 (8.7%)	24
Nausea	17/217 (7.8%)	20	20/218 (9.2%)	23
Vomiting	10/217 (4.6%)	18	15/218 (6.9%)	18
Constipation	10/217 (4.6%)	10	13/218 (6%)	13
General disorders
Pyrexia	12/217 (5.5%)	16	9/218 (4.1%)	10
Infections and infestations
Upper respiratory tract infection	12/217 (5.5%)	14	22/218 (10.1%)	24
Urinary tract infection	12/217 (5.5%)	15	10/218 (4.6%)	13
Injury, poisoning and procedural complications
Fall	13/217 (6%)	20	18/218 (8.3%)	31
Arteriovenous fistula site complication	15/217 (6.9%)	17	11/218 (5%)	16
Metabolism and nutrition disorders
Hyperkalaemia	12/217 (5.5%)	13	14/218 (6.4%)	14
Hypophosphataemia	10/217 (4.6%)	11	11/218 (5%)	12
Musculoskeletal and connective tissue disorders
Pain in extremity	12/217 (5.5%)	16	16/218 (7.3%)	18
Arthralgia	10/217 (4.6%)	10	13/218 (6%)	15
Muscle spasms	8/217 (3.7%)	8	14/218 (6.4%)	16
Nervous system disorders
Headache	15/217 (6.9%)	17	15/218 (6.9%)	18
Dizziness	9/217 (4.1%)	11	12/218 (5.5%)	14
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/217 (4.1%)	11	15/218 (6.9%)	18
Cough	2/217 (0.9%)	2	12/218 (5.5%)	12
Vascular disorders
Hypertension	24/217 (11.1%)	40	27/218 (12.4%)	34
Hypotension	9/217 (4.1%)	10	12/218 (5.5%)	12

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.