PEARL 1: Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis

• Sponsor: Affymax (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00598273
• Collaborator: Takeda (Industry)
• Enrollment: 490
• Locations: 72
• Arms: 3
• Duration (Months): 28.1
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of peginesatide for the treatment of anemia in participants with chronic kidney disease, who are not on dialysis and not on erythropoiesis stimulating agent (ESA) treatment.

Condition or Disease	Intervention/Treatment	Phase
Chronic Renal Failure; Chronic Kidney Disease; Anemia	Drug: peginesatide; Drug: peginesatide; Drug: Darbepoetin alfa	Phase 3

Detailed Description

Anemia associated with chronic kidney disease is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The presence and severity of anemia are related to the duration and extent of kidney failure. Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function, and increased left ventricular hypertrophy and heart failure.

Erythropoiesis stimulating agents have been established as a treatment for anemia in chronic renal failure subjects, and have improved the management of anemia over alternatives such as transfusion. Peginesatide is a parenteral formulation developed for the treatment of anemia in patients with chronic kidney disease. Peginesatide binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in a manner similar to other known erythropoiesis-stimulating agents.

Study participants received doses of peginesatide administered once every 4 weeks or darbepoetin alfa administered once every 2 weeks. Total commitment time for this study was a 4 week screening period followed by a minimum of 52 weeks of study treatment. Eligible participants were randomized in equal proportions to two peginesatide treatment regimens and one control, darbepoetin alfa, treatment regimen.

To evaluate the cardiovascular safety of peginesatide, a cardiovascular composite safety endpoint (CSE) was defined for use in prospectively planned analyses which combined cardiovascular safety data from the four Phase 3 peginesatide studies (NCT00598273, NCT00597753, NCT00598442, and NCT00597584). The CSE consisted of six events: death, stroke, myocardial infarction, and serious adverse events of congestive heart failure, unstable angina, and arrhythmia. An independent Event Review Committee (ERC) was used to provide blinded adjudication of potential CSE events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 490 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: AFX01-11: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Correction of Anemia in Patients With Chronic Renal Failure (CRF) Not on Dialysis and Not on Erythropoiesis Stimulating Agent (ESA) Treatment
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peginesatide 0.025 mg/kg	Drug: peginesatide; Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).; Other Names: Omontys Hematide AF37702 Injection
Experimental: Peginesatide 0.04 mg/kg	Drug: peginesatide; Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.; Other Names: Omontys Hematide AF37702 Injection
Active Comparator: Darbepoetin Alfa	Drug: Darbepoetin alfa; As prescribed, starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.; Other Names: Aranesp

Outcome Measures

Primary Outcome Measures

1. Mean Change in Hemoglobin Between Baseline and the Evaluation Period [Baseline and Weeks 25-36]

   The baseline hemoglobin value is defined as the mean of three hemoglobin values: the two most recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the Evaluation Period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 25 through 36.

Secondary Outcome Measures

1. Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods [Weeks 0 to 36]

2. Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods. [Weeks 0 to 36]

   A hemoglobin response is defined as hemoglobin increase of ≥ 1.0 gram per deciliter (g/dL) above baseline and a hemoglobin ≥ 11.0 g/dL without RBC transfusion during the previous 8 weeks.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Chronic renal failure with an estimated glomerular filtration rate < 60 milliliter per minute per 1.73m^2 and not expected to begin dialysis for at least 12 weeks.

2. Two consecutive hemoglobin values ≥ 8.0 g/dL and < 11.0 g/dL within 4 weeks prior to randomization.

Exclusion Criteria:

1. Females who are pregnant or breast-feeding.

2. Treatment with an ESA in the 12 weeks prior to randomization.

3. Known intolerance to any ESA, parenteral iron supplementation, or pegylated molecule.

4. Prior chronic hemodialysis or chronic peritoneal dialysis treatment.

5. Known bleeding or coagulation disorder.

6. Known hematologic disease or cause of anemia other than renal disease

7. Poorly controlled hypertension

8. Evidence of active malignancy within one year prior to randomization.

9. A scheduled kidney transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Facility	Montgomery	Alabama	United States	36106
2	Research Facility	Tempe	Arizona	United States	85306
3	Research Facility	Hot Springs	Arkansas	United States	71901
4	Research Facility	Bakersfield	California	United States	93309
5	Research Facility	Chula Vista	California	United States	91910
6	Research Facility	Glendale	California	United States	91204
7	Research Facility	Huntington Beach	California	United States	92646
8	Research Facility	Los Angeles	California	United States	90095
9	Research Facility	Orange	California	United States	92868
10	Research Facility	Paramount	California	United States	90723
11	Research Facility	Pasadena	California	United States	91106
12	Research Facility	Riverside	California	United States	92505
13	Research Facility	San Dimas	California	United States	91773
14	Research Facility	Stanford	California	United States	94305-6203
15	Research Facility	Whittier	California	United States	90603
16	Research Facility	Whittier	California	United States	90606
17	Research Facility	Yuba City	California	United States	95991
18	Research Facility	Thornton	Colorado	United States	80031
19	Research Facility	Washington	District of Columbia	United States	20037
20	Research Facility	Holly Hill	Florida	United States	32117
21	Research Facility	Hudson	Florida	United States	34667
22	Research Facility	Miami	Florida	United States	33173
23	Research Facility	Ocala	Florida	United States	34471
24	Research Facility	Orlando	Florida	United States	32804
25	Research Facility	Tampa	Florida	United States	33614
26	Research Facility	Augusta	Georgia	United States	30901
27	Research Facility	Honolulu	Hawaii	United States	96817
28	Research Facility	Chicago	Illinois	United States	60616
29	Research Facility	Evergreen Park	Illinois	United States	60805
30	Research Facility	Hines	Illinois	United States	60141
31	Research Facility	Evansville	Indiana	United States	47714
32	Research Facility	Lafayette	Indiana	United States	47904
33	Research Facility	Wichita	Kansas	United States	67214
34	Research Facility	Shreveport	Louisiana	United States	71101
35	Research Facility	Bethesda	Maryland	United States	20814
36	Research Facility	Fall River	Massachusetts	United States	02720
37	Research Facility	Worcester	Massachusetts	United States	01608
38	Research Facility	Midland	Michigan	United States	48640
39	Research Facility	Columbus	Mississippi	United States	39705
40	Research Facility	Kansas City	Missouri	United States	64128
41	Research Facility	Northfield	New Jersey	United States	08225
42	Research Facility	Toms River	New Jersey	United States	08755
43	Research Facility	Binghamton	New York	United States	13903
44	Research Facility	Great Neck	New York	United States	11021
45	Research Facility	Mineola	New York	United States	11501
46	Research Facility	Charlotte	North Carolina	United States	28208
47	Research Facility	Oklahoma City	Oklahoma	United States	73116
48	Research Facility	Bend	Oregon	United States	97701
49	Research Facility	Portland	Oregon	United States	97210
50	Research Facility	Allentown	Pennsylvania	United States	18103
51	Research Facility	Erie	Pennsylvania	United States	16507
52	Research Facility	Johnstown	Pennsylvania	United States	15905
53	Research Facility	Providence	Rhode Island	United States	02904
54	Research Facility	Orangeburg	South Carolina	United States	29118
55	Research Facility	Rock Hill	South Carolina	United States	29732
56	Research Facility	Clarksville	Tennessee	United States	37043
57	Research Facility	Knoxville	Tennessee	United States	37923
58	Research Facility	Nashville	Tennessee	United States	37205
59	Research Facility	Austin	Texas	United States	78705
60	Research Facility	Corpus Christi	Texas	United States	78404
61	Research Facility	Corsicana	Texas	United States	75110
62	Research Facility	Edinburg	Texas	United States	78539
63	Research Facility	Houston	Texas	United States	77030
64	Research Facility	Houston	Texas	United States	77099
65	Research Facility	San Antonio	Texas	United States	78215
66	Research Facility	San Antonio	Texas	United States	78229
67	Research Facility	Salem	Virginia	United States	24153
68	Research Facility	Bluefield	West Virginia	United States	24701
69	Research Facility	Caguas		Puerto Rico	00725
70	Research Facility	Ponce		Puerto Rico	00716
71	Research Facility	San Juan		Puerto Rico	00909
72	Research Facility	San Juan		Puerto Rico	00918

Sponsors and Collaborators

• Affymax
• Takeda

Investigators

• Study Director: Vice President, Clinical Development, Affymax

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Affymax
• ClinicalTrials.gov Identifier: NCT00598273
• Other Study ID Numbers: AFX01-11
• First Posted: Jan 21, 2008
• Last Update Posted: Feb 12, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Affymax: anemia; chronic kidney disease; CKD; chronic renal failure; CRF; erythropoietin; EPO; erythropoiesis stimulating agent; ESA; Hematide™; hemoglobin; Hb; Hgb; Omontys; peginesatide; red blood cell; red blood cell production
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Failure, Chronic; Anemia; Darbepoetin alfa

Study Results

Participant Flow

Arm/Group Title	Peginesatide 0.025 mg/kg	Peginesatide 0.04 mg/kg	Darbepoetin Alfa
Arm/Group Description	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received a starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks, as prescribed. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Period Title: Overall Study
STARTED	161	165	164
COMPLETED	120	127	125
NOT COMPLETED	41	38	39

Baseline Characteristics

Arm/Group Title	Peginesatide 0.025 mg/kg	Peginesatide 0.04 mg/kg	Darbepoetin Alfa	Total
Arm/Group Description	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received a starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks, as prescribed. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Total of all reporting groups
Overall Participants	161	165	164	490
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	70 43.5%	63 38.2%	65 39.6%	198 40.4%
>=65 years	91 56.5%	102 61.8%	99 60.4%	292 59.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.1 (13.51)	67.1 (12.73)	66.4 (14.25)	66.9 (13.49)
Sex: Female, Male (Count of Participants)
Female	93 57.8%	84 50.9%	102 62.2%	279 56.9%
Male	68 42.2%	81 49.1%	62 37.8%	211 43.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Hemoglobin Between Baseline and the Evaluation Period
Description	The baseline hemoglobin value is defined as the mean of three hemoglobin values: the two most recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the Evaluation Period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 25 through 36.
Time Frame	Baseline and Weeks 25-36

Outcome Measure Data

Analysis Population Description

Full Analysis Population: All randomized participants who received at least one dose of study medication

Arm/Group Title	Peginesatide 0.025 mg/kg	Peginesatide 0.04 mg/kg	Darbepoetin Alfa
Arm/Group Description	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received a starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks, as prescribed. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Measure Participants	161	165	164
Baseline [N=161, 165, 164]	10.05 (0.623)	9.95 (0.685)	10.05 (0.638)
Evaluation Period [N=141, 151, 151]	11.47 (0.731)	11.61 (0.856)	11.47 (0.747)
Change from Baseline [N=141, 151, 151]	1.39 (0.866)	1.64 (0.965)	1.37 (0.861)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.025 mg/kg, Darbepoetin Alfa
	Comments	The sample size for this study was determined based on a two-group evaluation of non-inferiority in means with a non-inferiority margin (Δ) of -1.0 g/dL (one-sided significance level of 0.0125, or, comparably, a two-sided significance level of 0.025). A sample size of 450 (150 per treatment group) provided power greater than 99% for the evaluation of non-inferiority, assuming an expected treatment difference of 0.0 g/dL and a pooled standard deviation of 1.5 g/dL.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A non-inferiority margin of -1.0 g/dL was used in the primary efficacy assessments. Non-inferiority was established if the lower limit of the two-sided 97.5% confidence interval for the difference between the means of the primary endpoint (peginesatide minus control ESA) was ≥ -1.0 g/dL.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 97.5%; -0.19 to 0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.099
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.04 mg/kg, Darbepoetin Alfa
	Comments	The sample size for this study was determined based on a two-group evaluation of non-inferiority in means with a non-inferiority margin (Δ) of -1.0 g/dL (one-sided significance level of 0.0125, or, comparably, a two-sided significance level of 0.025). A sample size of 450 (150 per treatment group) provided power greater than 99% for the evaluation of non-inferiority, assuming an expected treatment difference of 0.0 g/dL and a pooled standard deviation of 1.5 g/dL.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A non-inferiority margin of -1.0 g/dL was used in the primary efficacy assessments. Non-inferiority was established if the lower limit of the two-sided 97.5% confidence interval for the difference between the means of the primary endpoint (peginesatide minus control ESA) was ≥ -1.0 g/dL.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 97.5%; 0.04 to 0.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.098
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods
Time Frame	Weeks 0 to 36

Outcome Measure Data

Analysis Population Description

Full Analysis Population: All randomized participants who received at least one dose of study medication

Arm/Group Title	Peginesatide 0.025 mg/kg	Peginesatide 0.04 mg/kg	Darbepoetin Alfa
Arm/Group Description	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received a starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks, as prescribed. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Measure Participants	161	165	164
Number [percentage of participants]	0.062 0%	0.073 0%	0.049 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.025 mg/kg, Darbepoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 0.51 to 3.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.04 mg/kg, Darbepoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95%; 0.62 to 3.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods.
Description	A hemoglobin response is defined as hemoglobin increase of ≥ 1.0 gram per deciliter (g/dL) above baseline and a hemoglobin ≥ 11.0 g/dL without RBC transfusion during the previous 8 weeks.
Time Frame	Weeks 0 to 36

Outcome Measure Data

Analysis Population Description

Full Analysis Population: All randomized participants who received at least one dose of study medication

Arm/Group Title	Peginesatide 0.025 mg/kg	Peginesatide 0.04 mg/kg	Darbepoetin Alfa
Arm/Group Description	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received a starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks, as prescribed. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Measure Participants	161	165	164
Number [percentage of participants]	0.932 0.6%	0.939 0.6%	0.939 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.025 mg/kg, Darbepoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.04 mg/kg, Darbepoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Peginesatide 0.025 mg/kg		Peginesatide 0.04 mg/kg		Darbepoetin Alfa
Arm/Group Description	Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).		Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.		Participants received a starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks, as prescribed. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
All Cause Mortality
	Peginesatide 0.025 mg/kg		Peginesatide 0.04 mg/kg		Darbepoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Peginesatide 0.025 mg/kg		Peginesatide 0.04 mg/kg		Darbepoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/161 (47.8%)		75/165 (45.5%)		71/164 (43.3%)
Blood and lymphatic system disorders
Anaemia	5/161 (3.1%)		5/165 (3%)		1/164 (0.6%)
Haemorrhagic anaemia	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Coagulopathy	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Heparin-induced thrombocytopenia	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Normochromic normocytic anaemia	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Thrombocytopenia	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Cardiac disorders
Cardiac failure congestive	15/161 (9.3%)		16/165 (9.7%)		14/164 (8.5%)
Atrial fibrillation	3/161 (1.9%)		7/165 (4.2%)		3/164 (1.8%)
Myocardial infarction	1/161 (0.6%)		6/165 (3.6%)		4/164 (2.4%)
Acute myocardial infarction	4/161 (2.5%)		3/165 (1.8%)		1/164 (0.6%)
Bradycardia	1/161 (0.6%)		2/165 (1.2%)		4/164 (2.4%)
Coronary artery disease	2/161 (1.2%)		2/165 (1.2%)		3/164 (1.8%)
Angina pectoris	2/161 (1.2%)		1/165 (0.6%)		2/164 (1.2%)
Cardiac arrest	2/161 (1.2%)		2/165 (1.2%)		1/164 (0.6%)
Cardio-respiratory arrest	2/161 (1.2%)		1/165 (0.6%)		1/164 (0.6%)
Acute coronary syndrome	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Sick sinus syndrome	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Angina unstable	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Arrhythmia	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Atrial flutter	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Atrioventricular block complete	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Atrioventricular block first degree	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Atrioventricular block second degree	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Cardiac disorder	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Cardiac failure	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Coronary artery stenosis	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Hypertensive cardiomyopathy	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Ischaemic cardiomyopathy	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Nodal arrhythmia	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Pericardial effusion	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Sinus tachycardia	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Supraventricular extrasystoles	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Tachyarrhythmia	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Tachycardia	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Ventricular fibrillation	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Ear and labyrinth disorders
Vertigo	0/161 (0%)		1/165 (0.6%)		1/164 (0.6%)
Endocrine disorders
Adrenal insufficiency	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	4/161 (2.5%)		4/165 (2.4%)		0/164 (0%)
Diarrhoea	1/161 (0.6%)		2/165 (1.2%)		1/164 (0.6%)
Abdominal pain	2/161 (1.2%)		1/165 (0.6%)		0/164 (0%)
Diverticulum	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Gastritis	0/161 (0%)		0/165 (0%)		2/164 (1.2%)
Ileus	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Nausea	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Peritonitis	2/161 (1.2%)		0/165 (0%)		0/164 (0%)
Upper gastrointestinal haemorrhage	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Vomiting	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Abdominal wall haematoma	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Constipation	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Diverticular perforation	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Diverticulum intestinal haemorrhagic	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Duodenitis	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Enterocolitis haemorrhagic	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Enterocutaneous fistula	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Gastric ulcer	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Gastric varices haemorrhage	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Gastrooesophageal reflux disease	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Haematemesis	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Haemorrhagic ascites	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Haemorrhoidal haemorrhage	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Oesophagitis	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Pancreatitis	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Peritoneal haemorrhage	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Rectal fissure	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Rectal haemorrhage	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Retroperitoneal haemorrhage	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
General disorders
Chest pain	3/161 (1.9%)		0/165 (0%)		3/164 (1.8%)
Asthenia	2/161 (1.2%)		3/165 (1.8%)		0/164 (0%)
Non-cardiac chest pain	1/161 (0.6%)		1/165 (0.6%)		2/164 (1.2%)
Death	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Generalised oedema	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Sudden cardiac death	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Systemic inflammatory response syndrome	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Hepatobiliary disorders
Cholecystitis	2/161 (1.2%)		0/165 (0%)		2/164 (1.2%)
Cholelithiasis	2/161 (1.2%)		0/165 (0%)		2/164 (1.2%)
Cholecystitis acute	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Chronic hepatic failure	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Infections and infestations
Pneumonia	10/161 (6.2%)		8/165 (4.8%)		9/164 (5.5%)
Urinary tract infection	5/161 (3.1%)		9/165 (5.5%)		7/164 (4.3%)
Cellulitis	6/161 (3.7%)		5/165 (3%)		3/164 (1.8%)
Sepsis	4/161 (2.5%)		1/165 (0.6%)		3/164 (1.8%)
Osteomyelitis	0/161 (0%)		5/165 (3%)		1/164 (0.6%)
Bacteraemia	2/161 (1.2%)		1/165 (0.6%)		0/164 (0%)
Catheter sepsis	2/161 (1.2%)		0/165 (0%)		1/164 (0.6%)
Gastroenteritis	1/161 (0.6%)		0/165 (0%)		2/164 (1.2%)
Septic shock	1/161 (0.6%)		2/165 (1.2%)		0/164 (0%)
Upper respiratory tract infection	1/161 (0.6%)		2/165 (1.2%)		0/164 (0%)
Bronchitis	0/161 (0%)		1/165 (0.6%)		1/164 (0.6%)
Catheter related infection	0/161 (0%)		2/165 (1.2%)		0/164 (0%)
Clostridium difficile colitis	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Diverticulitis	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Endocarditis bacterial	0/161 (0%)		1/165 (0.6%)		1/164 (0.6%)
Infected skin ulcer	0/161 (0%)		1/165 (0.6%)		1/164 (0.6%)
Staphylococcal bacteraemia	0/161 (0%)		1/165 (0.6%)		1/164 (0.6%)
Urosepsis	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Wound infection staphylococcal	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Abscess limb	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Arthritis bacterial	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Bacterial sepsis	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Carbuncle	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Catheter site cellulitis	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Endocarditis enterococcal	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Escherichia urinary tract infection	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Fungaemia	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Gangrene	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Herpes zoster	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Influenza	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Labyrinthitis	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Lobar pneumonia	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Peritonitis bacterial	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Pneumonia necrotising	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Pneumonia staphylococcal	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Pseudomembranous colitis	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Pseudomonas infection	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Streptococcal bacteraemia	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Subcutaneous abscess	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Viral infection	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Vulval abscess	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Injury, poisoning and procedural complications
Fall	2/161 (1.2%)		0/165 (0%)		1/164 (0.6%)
Arteriovenous fistula thrombosis	0/161 (0%)		2/165 (1.2%)		0/164 (0%)
Femoral neck fracture	2/161 (1.2%)		0/165 (0%)		0/164 (0%)
Hip fracture	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Lower limb fracture	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Tibia fracture	2/161 (1.2%)		0/165 (0%)		0/164 (0%)
Anaemia postoperative	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Ankle fracture	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Arteriovenous fistula site complication	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Arteriovenous fistula site haemorrhage	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Arteriovenous graft thrombosis	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Cardiac pacemaker malfunction	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Contrast media reaction	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Drug toxicity	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Fibula fracture	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Foot fracture	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Humerus fracture	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Intentional overdose	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Post procedural haemorrhage	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Procedural pain	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Radius fracture	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Subdural haematoma	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Traumatic haematoma	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Urinary retention postoperative	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Investigations
Blood glucose increased	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Cardiac enzymes increased	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Electrocardiogram change	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Metabolism and nutrition disorders
Hyperkalaemia	4/161 (2.5%)		7/165 (4.2%)		1/164 (0.6%)
Dehydration	2/161 (1.2%)		4/165 (2.4%)		5/164 (3%)
Hypoglycaemia	2/161 (1.2%)		3/165 (1.8%)		5/164 (3%)
Fluid overload	1/161 (0.6%)		3/165 (1.8%)		2/164 (1.2%)
Hyponatraemia	1/161 (0.6%)		0/165 (0%)		3/164 (1.8%)
Diabetes mellitus inadequate control	0/161 (0%)		1/165 (0.6%)		1/164 (0.6%)
Diabetic ketoacidosis	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Hypernatraemia	0/161 (0%)		2/165 (1.2%)		0/164 (0%)
Hypokalaemia	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Diabetes mellitus	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Diabetic foot	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Electrolyte imbalance	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Failure to thrive	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Metabolic acidosis	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	2/161 (1.2%)		1/165 (0.6%)		0/164 (0%)
Osteoarthritis	0/161 (0%)		3/165 (1.8%)		0/164 (0%)
Rhabdomyolysis	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Arthralgia	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Arthropathy	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Chondrocalcinosis pyrophosphate	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Haemarthrosis	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Intervertebral disc protrusion	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Musculoskeletal chest pain	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	0/161 (0%)		2/165 (1.2%)		0/164 (0%)
Endometrial cancer	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Gastric cancer	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Liposarcoma	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Lung squamous cell carcinoma stage unspecified	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Metastatic gastric cancer	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Metastatic squamous cell carcinoma	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Multiple myeloma	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Transitional cell carcinoma	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Nervous system disorders
Syncope	2/161 (1.2%)		2/165 (1.2%)		1/164 (0.6%)
Dizziness	1/161 (0.6%)		1/165 (0.6%)		0/164 (0%)
Anoxic encephalopathy	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Carotid artery occlusion	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Carotid artery stenosis	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Cerebral infarction	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Cerebrovascular accident	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Convulsion	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Dementia	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Dizziness postural	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Embolic stroke	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Haemorrhagic stroke	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Hypertensive encephalopathy	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Lacunar infarction	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Syncope vasovagal	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Transient ischaemic attack	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Psychiatric disorders
Mental status changes	3/161 (1.9%)		0/165 (0%)		0/164 (0%)
Renal and urinary disorders
Renal failure acute	21/161 (13%)		13/165 (7.9%)		9/164 (5.5%)
Renal failure chronic	12/161 (7.5%)		3/165 (1.8%)		8/164 (4.9%)
Azotaemia	4/161 (2.5%)		3/165 (1.8%)		6/164 (3.7%)
Renal failure	5/161 (3.1%)		4/165 (2.4%)		4/164 (2.4%)
Haematuria	1/161 (0.6%)		2/165 (1.2%)		1/164 (0.6%)
Nephrotic syndrome	1/161 (0.6%)		0/165 (0%)		2/164 (1.2%)
Renal impairment	0/161 (0%)		1/165 (0.6%)		1/164 (0.6%)
Urinary retention	0/161 (0%)		2/165 (1.2%)		0/164 (0%)
Acute prerenal failure	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Cystitis erosive	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Nephrolithiasis	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Neurogenic bladder	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Obstructive uropathy	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Urethral stenosis	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	4/161 (2.5%)		1/165 (0.6%)		2/164 (1.2%)
Acute respiratory failure	0/161 (0%)		3/165 (1.8%)		2/164 (1.2%)
Pulmonary oedema	2/161 (1.2%)		1/165 (0.6%)		2/164 (1.2%)
Respiratory failure	2/161 (1.2%)		3/165 (1.8%)		0/164 (0%)
Asthma	1/161 (0.6%)		2/165 (1.2%)		0/164 (0%)
Pleural effusion	3/161 (1.9%)		0/165 (0%)		0/164 (0%)
Hypoxia	0/161 (0%)		0/165 (0%)		2/164 (1.2%)
Pneumonia aspiration	2/161 (1.2%)		0/165 (0%)		0/164 (0%)
Pneumothorax	0/161 (0%)		2/165 (1.2%)		0/164 (0%)
Atelectasis	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Dyspnoea	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Pneumonitis	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Pulmonary embolism	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Pulmonary mass	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Respiratory arrest	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/161 (0%)		1/165 (0.6%)		1/164 (0.6%)
Decubitus ulcer	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Vascular disorders
Hypertension	3/161 (1.9%)		5/165 (3%)		5/164 (3%)
Hypertensive crisis	1/161 (0.6%)		1/165 (0.6%)		2/164 (1.2%)
Hypotension	2/161 (1.2%)		1/165 (0.6%)		1/164 (0.6%)
Peripheral vascular disorder	1/161 (0.6%)		0/165 (0%)		2/164 (1.2%)
Aortic aneurysm	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Hypertensive emergency	2/161 (1.2%)		0/165 (0%)		0/164 (0%)
Malignant hypertension	1/161 (0.6%)		0/165 (0%)		1/164 (0.6%)
Aortic stenosis	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Arteriosclerosis	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Deep vein thrombosis	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Hypovolaemic shock	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Intermittent claudication	0/161 (0%)		1/165 (0.6%)		0/164 (0%)
Lymphoedema	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Orthostatic hypotension	1/161 (0.6%)		0/165 (0%)		0/164 (0%)
Peripheral artery dissection	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Steal syndrome	0/161 (0%)		0/165 (0%)		1/164 (0.6%)
Other (Not Including Serious) Adverse Events
	Peginesatide 0.025 mg/kg		Peginesatide 0.04 mg/kg		Darbepoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/161 (77%)		123/165 (74.5%)		116/164 (70.7%)
Endocrine disorders
Hyperparathyroidism secondary	13/161 (8.1%)		4/165 (2.4%)		6/164 (3.7%)
Gastrointestinal disorders
Nausea	27/161 (16.8%)		15/165 (9.1%)		22/164 (13.4%)
Vomiting	23/161 (14.3%)		10/165 (6.1%)		15/164 (9.1%)
Diarrhoea	22/161 (13.7%)		17/165 (10.3%)		22/164 (13.4%)
Constipation	20/161 (12.4%)		15/165 (9.1%)		16/164 (9.8%)
Gastrooesophageal reflux disease	11/161 (6.8%)		11/165 (6.7%)		8/164 (4.9%)
Abdominal pain	9/161 (5.6%)		6/165 (3.6%)		4/164 (2.4%)
General disorders
Oedema peripheral	31/161 (19.3%)		27/165 (16.4%)		18/164 (11%)
Fatigue	15/161 (9.3%)		7/165 (4.2%)		15/164 (9.1%)
Pyrexia	11/161 (6.8%)		6/165 (3.6%)		6/164 (3.7%)
Oedema	7/161 (4.3%)		11/165 (6.7%)		3/164 (1.8%)
Infections and infestations
Urinary tract infection	22/161 (13.7%)		24/165 (14.5%)		24/164 (14.6%)
Nasopharyngitis	15/161 (9.3%)		18/165 (10.9%)		11/164 (6.7%)
Upper respiratory tract infection	15/161 (9.3%)		17/165 (10.3%)		15/164 (9.1%)
Bronchitis	9/161 (5.6%)		5/165 (3%)		7/164 (4.3%)
Cellulitis	8/161 (5%)		9/165 (5.5%)		3/164 (1.8%)
Influenza	8/161 (5%)		9/165 (5.5%)		4/164 (2.4%)
Injury, poisoning and procedural complications
Contusion	12/161 (7.5%)		8/165 (4.8%)		6/164 (3.7%)
Fall	12/161 (7.5%)		15/165 (9.1%)		8/164 (4.9%)
Metabolism and nutrition disorders
Hyperkalaemia	32/161 (19.9%)		22/165 (13.3%)		27/164 (16.5%)
Hyperphosphataemia	22/161 (13.7%)		8/165 (4.8%)		11/164 (6.7%)
Metabolic acidosis	11/161 (6.8%)		7/165 (4.2%)		13/164 (7.9%)
Hypoglycaemia	10/161 (6.2%)		8/165 (4.8%)		11/164 (6.7%)
Hypokalaemia	8/161 (5%)		11/165 (6.7%)		4/164 (2.4%)
Gout	7/161 (4.3%)		9/165 (5.5%)		7/164 (4.3%)
Musculoskeletal and connective tissue disorders
Pain in extremity	21/161 (13%)		15/165 (9.1%)		12/164 (7.3%)
Arthralgia	19/161 (11.8%)		19/165 (11.5%)		14/164 (8.5%)
Back pain	16/161 (9.9%)		17/165 (10.3%)		12/164 (7.3%)
Muscle spasms	16/161 (9.9%)		17/165 (10.3%)		17/164 (10.4%)
Musculoskeletal pain	8/161 (5%)		11/165 (6.7%)		5/164 (3%)
Nervous system disorders
Headache	15/161 (9.3%)		12/165 (7.3%)		13/164 (7.9%)
Dizziness	14/161 (8.7%)		19/165 (11.5%)		24/164 (14.6%)
Psychiatric disorders
Insomnia	11/161 (6.8%)		8/165 (4.8%)		11/164 (6.7%)
Anxiety	9/161 (5.6%)		12/165 (7.3%)		7/164 (4.3%)
Respiratory, thoracic and mediastinal disorders
Cough	23/161 (14.3%)		14/165 (8.5%)		8/164 (4.9%)
Dyspnoea	17/161 (10.6%)		14/165 (8.5%)		13/164 (7.9%)
Skin and subcutaneous tissue disorders
Rash	17/161 (10.6%)		9/165 (5.5%)		8/164 (4.9%)
Vascular disorders
Hypertension	24/161 (14.9%)		16/165 (9.7%)		17/164 (10.4%)
Hypotension	7/161 (4.3%)		10/165 (6.1%)		16/164 (9.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first publication of the primary safety and efficacy results will include data from all appropriate study sites. Either after the first multicenter publication, or following 36 months after the completion of the study, Investigators are free to publish; such publications may not contain Sponsor Confidential Information and may be subject to Sponsor review 60 days prior to submission for publication.