Efficacy and Safety of Peginesatide Injection for the Maintenance Treatment of Anemia in Peritoneal Dialysis Participants Previously Treated With Epoetin.

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00752791
• Collaborator: Affymax (Industry)
• Enrollment: 59
• Locations: 23
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of peginesatide injection for maintenance treatment of anemia in participants on peritoneal dialysis.

Condition or Disease	Intervention/Treatment	Phase
Anemia	Drug: Peginesatide	Phase 2

Detailed Description

According to the International Federation of Renal Registries, in 1999 the prevalence of peritoneal dialysis in the United States as approximately 9.5% of patients receiving dialysis (2005 United States Renal Data Systems data indicates a prevalence of around 7.5%). Data from Europe in 1999 to 2000 (not including the United Kingdom, France or Germany) indicated peritoneal dialysis was the mode of dialysis in approximately 11.1% of dialysis patients. 2006 data from the United Kingdom indicates that more than 20% of patients on dialysis are receiving peritoneal dialysis while French and German data indicate rates of 8.1% and 4.8% respectively. More than 90% of patients with chronic renal failure/chronic kidney disease Stage 5 (End Stage Renal Disease) are anemic. The vast majority of patients receiving hemodialysis or peritoneal dialysis receive erythropoiesis-stimulating agent therapy to treat their anemia.

Anemia of chronic renal failure is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors also include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The prevalence of anemia increases with progressive deterioration of renal function, and affects more than 90% of patients with chronic kidney disease (CKD) Stage 5 (End Stage Renal Disease). Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function and exercise capacity, increased left ventricular hypertrophy and heart failure. Treatment of anemia reduces morbidity and mortality risks and may improve quality of life.

Erythropoiesis stimulating agents have been established as a treatment for anemia in chronic renal failure participants, and have improved the management of anemia over alternatives such as transfusion. Peginesatide (hematide) is a parenteral formulation being developed for the correction of anemia in patients with chronic renal failure, and 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.

Participants in this study received variable doses of peginesatide injection once every four weeks. Total commitment time for this study was about 29 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of the Safety and Efficacy of Hematide Injection for the Maintenance Treatment of Anemia in Peritoneal Dialysis Subjects Previously Treated With Epoetin
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peginesatide	Drug: Peginesatide; Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.; Other Names: Hematide AF37702 Omontys

Outcome Measures

Primary Outcome Measures

1. Mean Change in Hemoglobin Between Baseline and the Evaluation Period [Baseline and Week 20 to Week 25.]

   The primary efficacy endpoint was the mean change in Hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to Enrollment and the hemoglobin on the day of Enrollment) and the Evaluation Period (mean hemoglobin from Weeks 20 to 25).

Secondary Outcome Measures

1. Percentage of Participants With Hemoglobin Within the Target Range of 10.0 to 12.0 g/dL During the Evaluation Period [Week 20 to Week 25.]

   Mean hemoglobin was calculated from measurements taken during the Evaluation Period (Week 20 to Week 25). The target hemoglobin range was 10.0 to 12.0 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction.

2. Percentage of Participants With a Change in Hemoglobin From Baseline to the Evaluation Period Within 1 g/dL [Baseline and Week 20 to Week 25.]

   Percentage of participants with a mean change in Hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to enrollment and the hemoglobin on the day of enrollment) and the Evaluation Period (mean hemoglobin from measured at Weeks 20 to 25) of less than or equal ± 1 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction.

3. Percentage of Participants With Red Blood Cell Transfusions [Up to 25 weeks.]

   The percentage of participants who received one or more red blood cell transfusions, including packed red blood cells and whole blood transfusions, during the Titration Period (Weeks 1 - 19) and Evaluation Period (Weeks 20 -25). 95% Confidence Intervals were calculated from the normal approximation with continuity correction. One patient had the last study visit during the titration period and the transfusion after the titration period. This patient is excluded from the summary of evaluation period.

4. Mean Hemoglobin During 4-week Intervals [Up to 25 weeks.]

   Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 1-19) and weekly during the Evaluation Period (Weeks 20-25). One patient did not have central lab hemoglobin value during a regularly scheduled visit during weeks 2-5.

5. Percentage of Participants With Target Hemoglobin of 10.0 to 12.0 g/dL by 4-week Intervals [Up to 25 weeks.]

   Percentage of participants with mean hemoglobin levels falling between the target level of 10.0 to 12.0 g/dL during 4-week study intervals. Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 1-19) and weekly during the Evaluation Period (Weeks 20-25). 95% Confidence Intervals were calculated from the normal approximation with continuity correction.

6. Percentage of Participants With Dose Adjustments During the Study [From Week 4 to Week 25]

   The peginesatide dose was adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline during the Titration Period (Weeks 1-19) and Evaluation Period (Weeks 20-25). A dose was classified as adjusted if it was not within 20% of the previous dose. A dose was classified as increased or decreased if it was >20% higher or >20% lower respectively, than the previous dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The patient was a man or woman and 18 to 90 years of age, inclusive.

2. The patient had CKD and had been on peritoneal dialysis for ≥3 months before enrollment.

3. The patient was on stable SC epoetin (alfa or beta) maintenance therapy continuously prescribed for a minimum of 8 weeks prior to enrollment.

4. The patient had 4 consecutive Hb values with a mean ≥10.0 and ≤12.0 g/dL during the screening period, with the difference between the mean of the first confirmed (2 consecutive) Hb values and the mean of the last confirmed (2 consecutive) Hb values being ≤1.0 g/dL.

5. The patient had 1 ferritin level ≥100 ng/mL within 4 weeks before enrollment.

Exclusion Criteria:

1. The patient had known bleeding or coagulation disorder.

2. The patient had known hematologic disease or cause of anemia other than renal disease (e.g., pure red cell aplasia, homozygous sickle-cell disease, thalassemia, multiple myeloma, hemolytic anemia, and myelodysplastic syndrome).

3. The patient had received a recent course of intensive iron replacement (i.e., more than 500 mg IV in the 28 days before enrollment).

4. The patient had advanced chronic congestive heart failure defined by New York Heart Association Class III or IV.

5. The patient had a known history of seizure disorder or received antiepileptic medication for a seizure disorder within 6 months before enrollment.

6. The patient had a scheduled kidney transplant. (Note: patients who were currently on a transplant waiting list were not excluded unless there was an identified donor).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Azusa	California	United States
2		Los Angeles	California	United States
3		Whittier	California	United States
4		Naples	Florida	United States
5		Decatur	Georgia	United States
6		Evergreen Park	Illinois	United States
7		Wichita	Kansas	United States
8		Baton Rouge	Louisiana	United States
9		New Iberia	Louisiana	United States
10		Shreveport	Louisiana	United States
11		Columbus	Mississippi	United States
12		Tupelo	Mississippi	United States
13		New York	New York	United States
14		Williamsville	New York	United States
15		Canton	Ohio	United States
16		Arlington	Texas	United States
17		Tyler	Texas	United States
18		Fairfax	Virginia	United States
19		Mechanicsville	Virginia	United States
20		New Lambtom	New South Wales	Australia
21		Modena		Italy
22		Dunedin		New Zealand
23		London	England	United Kingdom

Sponsors and Collaborators

• Takeda
• Affymax

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00752791
• Other Study ID Numbers: AFX01_201; 2008-003458-13; U1111-1114-0301
• First Posted: Sep 15, 2008
• Last Update Posted: Aug 15, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Takeda: Anemia; Drug Therapy; Peritoneal Dialysis.
• Additional relevant MeSH terms: Anemia

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 26 sites in Australia, Italy, New Zealand, the United Kingdom and the United States from 31 October 2008 to 19 May 2010.
Pre-assignment Detail	Participants with chronic renal failure on peritoneal dialysis and receiving stable Epoetin (alfa or beta) maintenance therapy were enrolled into 1 treatment group (peginesatide injection).

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Period Title: Overall Study
STARTED	59
COMPLETED	43
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Overall Participants	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.0 (15.99)
Age, Customized (participants) [Number]
<65 years	42 71.2%
≥65 to <75 years	10 16.9%
≥75 years	7 11.9%
Sex: Female, Male (Count of Participants)
Female	32 54.2%
Male	27 45.8%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Hemoglobin Between Baseline and the Evaluation Period
Description	The primary efficacy endpoint was the mean change in Hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to Enrollment and the hemoglobin on the day of Enrollment) and the Evaluation Period (mean hemoglobin from Weeks 20 to 25).
Time Frame	Baseline and Week 20 to Week 25.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all patients who received at least 1 dose of peginesatide injection and where data was available at both time points (indicated by N).

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	59
Baseline [N=59]	11.22 (0.495)
Evaluation Period [N=46]	11.33 (1.066)
Change from Baseline [N=46]	0.10 (1.154)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean change from Baseline
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.24 to 0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	A two-sided 95% CI of the estimated mean change from Baseline in hemoglobin was derived from the t-distribution.

2. Secondary Outcome

Title	Percentage of Participants With Hemoglobin Within the Target Range of 10.0 to 12.0 g/dL During the Evaluation Period
Description	Mean hemoglobin was calculated from measurements taken during the Evaluation Period (Week 20 to Week 25). The target hemoglobin range was 10.0 to 12.0 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction.
Time Frame	Week 20 to Week 25.

Outcome Measure Data

Analysis Population Description

Full analysis set where data was available.

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	46
Number (95% Confidence Interval) [percentage of participants]	63.0 106.8%

3. Secondary Outcome

Title	Percentage of Participants With a Change in Hemoglobin From Baseline to the Evaluation Period Within 1 g/dL
Description	Percentage of participants with a mean change in Hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to enrollment and the hemoglobin on the day of enrollment) and the Evaluation Period (mean hemoglobin from measured at Weeks 20 to 25) of less than or equal ± 1 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction.
Time Frame	Baseline and Week 20 to Week 25.

Outcome Measure Data

Analysis Population Description

Full analysis set where data was available.

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	46
Number (95% Confidence Interval) [percentage of participants]	60.9 103.2%

4. Secondary Outcome

Title	Percentage of Participants With Red Blood Cell Transfusions
Description	The percentage of participants who received one or more red blood cell transfusions, including packed red blood cells and whole blood transfusions, during the Titration Period (Weeks 1 - 19) and Evaluation Period (Weeks 20 -25). 95% Confidence Intervals were calculated from the normal approximation with continuity correction. One patient had the last study visit during the titration period and the transfusion after the titration period. This patient is excluded from the summary of evaluation period.
Time Frame	Up to 25 weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	59
Entire study (n=59)	10.2 17.3%
Titration Period (n=59)	5.1 8.6%
Evaluation period (n=47)	4.3 7.3%

5. Secondary Outcome

Title	Mean Hemoglobin During 4-week Intervals
Description	Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 1-19) and weekly during the Evaluation Period (Weeks 20-25). One patient did not have central lab hemoglobin value during a regularly scheduled visit during weeks 2-5.
Time Frame	Up to 25 weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set where data was available for each time interval (indicated by N).

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	59
Week 2-5 [N=58]	11.57 (0.741)
Week 6-9 [N=56]	11.65 (1.044)
Week 10-13 [N=54]	11.53 (1.119)
Week 14-17 [N=52]	11.33 (1.037)
Week 18-21 [N=45]	11.46 (1.004)
Week 22-25 [N=46]	11.25 (1.122)

6. Secondary Outcome

Title	Percentage of Participants With Target Hemoglobin of 10.0 to 12.0 g/dL by 4-week Intervals
Description	Percentage of participants with mean hemoglobin levels falling between the target level of 10.0 to 12.0 g/dL during 4-week study intervals. Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 1-19) and weekly during the Evaluation Period (Weeks 20-25). 95% Confidence Intervals were calculated from the normal approximation with continuity correction.
Time Frame	Up to 25 weeks.

Outcome Measure Data

Analysis Population Description

Full analysis set where data was available for each time interval (indicated by N).

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	59
Week 2-5 [N=58]	67.2 113.9%
Week 6-9 [N=56]	53.6 90.8%
Week 10-13 [N=54]	59.3 100.5%
Week 14-17 [N=52]	61.5 104.2%
Week 18-21 [N=45]	64.4 109.2%
Week 22-25 [N=46]	63.0 106.8%

7. Secondary Outcome

Title	Percentage of Participants With Dose Adjustments During the Study
Description	The peginesatide dose was adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline during the Titration Period (Weeks 1-19) and Evaluation Period (Weeks 20-25). A dose was classified as adjusted if it was not within 20% of the previous dose. A dose was classified as increased or decreased if it was >20% higher or >20% lower respectively, than the previous dose.
Time Frame	From Week 4 to Week 25

Outcome Measure Data

Analysis Population Description

Safety Analysis Set. N indicates the number of patients with study drug administered during the period after excluding the initial dose of study drug and excluding the first dose after a restart of study drug and is the denominator for percentage calculations.

Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	59
Any adjustment in Titration Period [N=57]	80.7 136.8%
Any adjustment in Evaluation Period [N=42]	52.4 88.8%
Dose increased in Titration Period [N=57]	28.1 47.6%
Dose increased in Evaluation Period [N=42]	16.7 28.3%
Dose decreased in Titration Period [N=57]	66.7 113.1%
Dose decreased in Evaluation Period [N=42]	35.7 60.5%

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that occurred on or after the day of the first dose of peginesatide injection through the Follow-up phone call, which occurred within 28 days after the last dose.
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Peginesatide
Arm/Group Description	Peginesatide 0.04 to 0.16 mg/kg, subcutaneous injection, once every 4 weeks for up to 25 weeks. Initial dose based on patient's previous total weekly Epoetin dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
All Cause Mortality
	Peginesatide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Peginesatide
	Affected / at Risk (%)	# Events
Total	27/59 (45.8%)
Blood and lymphatic system disorders
Leukocytosis	1/59 (1.7%)
Cardiac disorders
Angina pectoris	1/59 (1.7%)
Atrial fibrillation	1/59 (1.7%)
Cardiac failure congestive	1/59 (1.7%)
Myocardial ischaemia	1/59 (1.7%)
Ventricular fibrillation	1/59 (1.7%)
Gastrointestinal disorders
Peritonitis	9/59 (15.3%)
Colonic polyp	1/59 (1.7%)
Diverticular perforation	1/59 (1.7%)
Gastrointestinal haemorrhage	1/59 (1.7%)
Peritoneal haemorrhage	1/59 (1.7%)
General disorders
Medical device complication	1/59 (1.7%)
Hepatobiliary disorders
Cholecystitis	1/59 (1.7%)
Infections and infestations
Abdominal abscess	1/59 (1.7%)
Catheter site infection	1/59 (1.7%)
Diabetic foot infection	1/59 (1.7%)
Fungal peritonitis	1/59 (1.7%)
Sepsis	1/59 (1.7%)
Septic shock	1/59 (1.7%)
Injury, poisoning and procedural complications
Avulsion fracture	1/59 (1.7%)
Fall	1/59 (1.7%)
Joint dislocation	1/59 (1.7%)
Tibia fracture	1/59 (1.7%)
Metabolism and nutrition disorders
Cachexia	1/59 (1.7%)
Fluid overload	1/59 (1.7%)
Hypokalaemia	1/59 (1.7%)
Nervous system disorders
Cerebrovascular accident	1/59 (1.7%)
Myasthenia gravis	1/59 (1.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/59 (3.4%)
Respiratory failure	2/59 (3.4%)
Nasal polyps	1/59 (1.7%)
Pulmonary Oedema	1/59 (1.7%)
Sleep apnoea syndrome	1/59 (1.7%)
Skin and subcutaneous tissue disorders
Pseudoporphyria	1/59 (1.7%)
Vascular disorders
Hypertensive crisis	1/59 (1.7%)
Peripheral vascular disorder	1/59 (1.7%)
Other (Not Including Serious) Adverse Events
	Peginesatide
	Affected / at Risk (%)	# Events
Total	41/59 (69.5%)
Gastrointestinal disorders
Diarrhoea	9/59 (15.3%)
Peritonitis	6/59 (10.2%)
Constipation	5/59 (8.5%)
Nausea	5/59 (8.5%)
Vomiting	5/59 (8.5%)
General disorders
Oedema Peripheral	5/59 (8.5%)
Infections and infestations
Urinary Tract Infection	5/59 (8.5%)
Catheter Site Infection	4/59 (6.8%)
Nasopharygitis	4/59 (6.8%)
Sinusitis	4/59 (6.8%)
Cellulitis	3/59 (5.1%)
Injury, poisoning and procedural complications
Excoriation	3/59 (5.1%)
Metabolism and nutrition disorders
Hypokalaemia	4/59 (6.8%)
Hypercalcaemia	3/59 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/59 (5.1%)
Nervous system disorders
Dizziness	3/59 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	6/59 (10.2%)
Dyspnoea	6/59 (10.2%)
Skin and subcutaneous tissue disorders
Rash	4/59 (6.8%)
Vascular disorders
Hypertension	8/59 (13.6%)
Hypotension	6/59 (10.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.