Safety and Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis (PEARL 2)

This study has been completed.

Sponsor:

Collaborator:

Takeda Pharmaceutical Company Limited

Information provided by (Responsible Party):

Affymax

ClinicalTrials.gov Identifier:

NCT00598442

First received: January 10, 2008

Last updated: February 6, 2013

Last verified: February 2013

History of Changes

Results First Received: April 26, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Chronic Renal Failure Chronic Kidney Disease Anemia
Interventions:	Drug: peginesatide Drug: Darbepoetin alfa

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Peginesatide 0.025 mg/kg	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).
Peginesatide 0.04 mg/kg	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.
Darbepoetin Alfa	Participants received darbepoetin alfa by subcutaneous injection once every 2 weeks, as prescribed. The starting dose was 0.75 microgram per kilogram (mcg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.

Participant Flow: Overall Study

	Peginesatide 0.025 mg/kg	Peginesatide 0.04 mg/kg	Darbepoetin Alfa
STARTED	167	163	163
COMPLETED	124	124	139
NOT COMPLETED	43	39	24
Adverse Event	3	0	0
Death	19	11	11
Lost to Follow-up	4	3	3
Physician Decision	2	1	1
Withdrawal by Subject	8	16	6
Noncompliance	0	2	1
Relocation	1	4	0
Renal transplant	0	0	1
Site closed by sponsor	5	2	1
Started dialysis	1	0	0

Baseline Characteristics

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Reporting Groups

	Description
Peginesatide 0.025 mg/kg	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).
Peginesatide 0.04 mg/kg	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.
Darbepoetin Alfa	Participants received darbepoetin alfa by subcutaneous injection once every 2 weeks, as prescribed. The starting dose was 0.75 microgram per kilogram (mcg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Total	Total of all reporting groups

Baseline Measures

	Peginesatide 0.025 mg/kg	Peginesatide 0.04 mg/kg	Darbepoetin Alfa	Total
Number of Participants [units: participants]	167	163	163	493
Age [units: participants]
<=18 years	0	0	0	0
Between 18 and 65 years	63	57	62	182
>=65 years	104	106	101	311
Age [units: years] Mean ± Standard Deviation	68.1 ± 12.93	68.3 ± 13.53	67.2 ± 15.03	67.9 ± 13.83
Gender [units: participants]
Female	93	96	99	288
Male	74	67	64	205

Outcome Measures

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1. Primary:

Mean Change in Hemoglobin Between Baseline and the Evaluation Period [ Time Frame: Baseline and Weeks 25-36 ]

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2. Secondary:

Proportion of Participants Who Received Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods [ Time Frame: Weeks 0 to 36 ]

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3. Secondary:

Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods [ Time Frame: Weeks 0 to 36 ]

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Serious Adverse Events

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Other Adverse Events

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Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Peginesatide 0.025 mg/kg	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).
Peginesatide 0.04 mg/kg	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.
Darbepoetin Alfa	Participants received darbepoetin alfa by subcutaneous injection once every 2 weeks, as prescribed. The starting dose was 0.75 microgram per kilogram (mcg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.

Other Adverse Events

	Peginesatide 0.025 mg/kg	Peginesatide 0.04 mg/kg	Darbepoetin Alfa
Total, other (not including serious) adverse events
# participants affected / at risk	142/167	134/163	134/163
Blood and lymphatic system disorders
Anaemia ^{† 1}
# participants affected / at risk	13/167 (7.78%)	9/163 (5.52%)	4/163 (2.45%)
Endocrine disorders
Hyperparathyroidism ^{† 1}
# participants affected / at risk	8/167 (4.79%)	4/163 (2.45%)	9/163 (5.52%)
Hyperparathyroidism secondary ^{† 1}
# participants affected / at risk	5/167 (2.99%)	9/163 (5.52%)	6/163 (3.68%)
Gastrointestinal disorders
Nausea ^{† 1}
# participants affected / at risk	27/167 (16.17%)	25/163 (15.34%)	27/163 (16.56%)
Diarrhoea ^{† 1}
# participants affected / at risk	22/167 (13.17%)	21/163 (12.88%)	32/163 (19.63%)
Vomiting ^{† 1}
# participants affected / at risk	17/167 (10.18%)	23/163 (14.11%)	15/163 (9.20%)
Constipation ^{† 1}
# participants affected / at risk	12/167 (7.19%)	16/163 (9.82%)	18/163 (11.04%)
Gastrooesophageal reflux disease ^{† 1}
# participants affected / at risk	12/167 (7.19%)	9/163 (5.52%)	5/163 (3.07%)
Abdominal pain ^{† 1}
# participants affected / at risk	9/167 (5.39%)	5/163 (3.07%)	7/163 (4.29%)
Abdominal pain upper ^{† 1}
# participants affected / at risk	8/167 (4.79%)	6/163 (3.68%)	9/163 (5.52%)
General disorders
Oedema peripheral ^{† 1}
# participants affected / at risk	45/167 (26.95%)	26/163 (15.95%)	34/163 (20.86%)
Fatigue ^{† 1}
# participants affected / at risk	15/167 (8.98%)	18/163 (11.04%)	14/163 (8.59%)
Asthenia ^{† 1}
# participants affected / at risk	12/167 (7.19%)	8/163 (4.91%)	8/163 (4.91%)
Pain ^{† 1}
# participants affected / at risk	10/167 (5.99%)	2/163 (1.23%)	3/163 (1.84%)
Infections and infestations
Nasopharyngitis ^{† 1}
# participants affected / at risk	22/167 (13.17%)	19/163 (11.66%)	24/163 (14.72%)
Urinary tract infection ^{† 1}
# participants affected / at risk	22/167 (13.17%)	22/163 (13.50%)	22/163 (13.50%)
Upper respiratory tract infection ^{† 1}
# participants affected / at risk	12/167 (7.19%)	15/163 (9.20%)	19/163 (11.66%)
Bronchitis ^{† 1}
# participants affected / at risk	5/167 (2.99%)	14/163 (8.59%)	13/163 (7.98%)
Sinusitis ^{† 1}
# participants affected / at risk	5/167 (2.99%)	5/163 (3.07%)	12/163 (7.36%)
Injury, poisoning and procedural complications
Fall ^{† 1}
# participants affected / at risk	16/167 (9.58%)	11/163 (6.75%)	10/163 (6.13%)
Contusion ^{† 1}
# participants affected / at risk	13/167 (7.78%)	11/163 (6.75%)	5/163 (3.07%)
Metabolism and nutrition disorders
Hyperkalaemia ^{† 1}
# participants affected / at risk	23/167 (13.77%)	24/163 (14.72%)	23/163 (14.11%)
Hyperphosphataemia ^{† 1}
# participants affected / at risk	16/167 (9.58%)	6/163 (3.68%)	15/163 (9.20%)
Gout ^{† 1}
# participants affected / at risk	11/167 (6.59%)	4/163 (2.45%)	9/163 (5.52%)
Hypoglycaemia ^{† 1}
# participants affected / at risk	10/167 (5.99%)	11/163 (6.75%)	6/163 (3.68%)
Iron deficiency ^{† 1}
# participants affected / at risk	10/167 (5.99%)	4/163 (2.45%)	4/163 (2.45%)
Metabolic acidosis ^{† 1}
# participants affected / at risk	10/167 (5.99%)	3/163 (1.84%)	8/163 (4.91%)
Anorexia ^{† 1}
# participants affected / at risk	9/167 (5.39%)	4/163 (2.45%)	7/163 (4.29%)
Hypokalaemia ^{† 1}
# participants affected / at risk	6/167 (3.59%)	7/163 (4.29%)	9/163 (5.52%)
Musculoskeletal and connective tissue disorders
Arthralgia ^{† 1}
# participants affected / at risk	23/167 (13.77%)	16/163 (9.82%)	14/163 (8.59%)
Back pain ^{† 1}
# participants affected / at risk	21/167 (12.57%)	18/163 (11.04%)	10/163 (6.13%)
Pain in extremity ^{† 1}
# participants affected / at risk	14/167 (8.38%)	17/163 (10.43%)	17/163 (10.43%)
Musculoskeletal pain ^{† 1}
# participants affected / at risk	9/167 (5.39%)	10/163 (6.13%)	7/163 (4.29%)
Muscle spasms ^{† 1}
# participants affected / at risk	8/167 (4.79%)	4/163 (2.45%)	14/163 (8.59%)
Nervous system disorders
Dizziness ^{† 1}
# participants affected / at risk	17/167 (10.18%)	20/163 (12.27%)	20/163 (12.27%)
Headache ^{† 1}
# participants affected / at risk	15/167 (8.98%)	15/163 (9.20%)	12/163 (7.36%)
Psychiatric disorders
Insomnia ^{† 1}
# participants affected / at risk	13/167 (7.78%)	7/163 (4.29%)	7/163 (4.29%)
Depression ^{† 1}
# participants affected / at risk	11/167 (6.59%)	7/163 (4.29%)	7/163 (4.29%)
Anxiety ^{† 1}
# participants affected / at risk	10/167 (5.99%)	7/163 (4.29%)	3/163 (1.84%)
Renal and urinary disorders
Renal failure chronic ^{† 1}
# participants affected / at risk	9/167 (5.39%)	4/163 (2.45%)	13/163 (7.98%)
Respiratory, thoracic and mediastinal disorders
Cough ^{† 1}
# participants affected / at risk	16/167 (9.58%)	17/163 (10.43%)	15/163 (9.20%)
Dyspnoea ^{† 1}
# participants affected / at risk	12/167 (7.19%)	17/163 (10.43%)	16/163 (9.82%)
Vascular disorders
Hypertension ^{† 1}
# participants affected / at risk	32/167 (19.16%)	24/163 (14.72%)	34/163 (20.86%)
Hypotension ^{† 1}
# participants affected / at risk	15/167 (8.98%)	13/163 (7.98%)	18/163 (11.04%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA (11.0)

More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Vice President, Clinical Development
Organization: Affymax
phone: 650-812-8700
e-mail: info@affymax.com

Publications of Results:

Macdougall IC, Provenzano R, Sharma A, Spinowitz BS, Schmidt RJ, Pergola PE, Zabaneh RI, Tong-Starksen S, Mayo MR, Tang H, Polu KR, Duliege AM, Fishbane S; PEARL Study Groups. Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis. N Engl J Med. 2013 Jan 24;368(4):320-32. doi: 10.1056/NEJMoa1203166.

Publications automatically indexed to this study:

Fishbane S, Schiller B, Locatelli F, Covic AC, Provenzano R, Wiecek A, Levin NW, Kaplan M, Macdougall IC, Francisco C, Mayo MR, Polu KR, Duliege AM, Besarab A; EMERALD Study Groups. Peginesatide in patients with anemia undergoing hemodialysis. N Engl J Med. 2013 Jan 24;368(4):307-19. doi: 10.1056/NEJMoa1203165.

Responsible Party:	Affymax
ClinicalTrials.gov Identifier:	NCT00598442 History of Changes
Other Study ID Numbers:	AFX01-13, 2007-004146-32
Study First Received:	January 10, 2008
Results First Received:	April 26, 2012
Last Updated:	February 6, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board Bulgaria: Bulgarian Drug Agency Bulgaria: Ethics committee Czech Republic: State Institute for Drug Control Czech Republic: Ethics Committee Germany: Federal Institute for Drugs and Medical Devices Germany: Ethics Commission Hungary: National Institute of Pharmacy Hungary: Scientific and Medical Research Council Ethics Committee Italy: The Italian Medicines Agency Italy: Ethics Committee Poland: The Central Register of Clinical Trials Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Poland: Ethics Committee Romania: National Medicines Agency Romania: Ethics Committee United Kingdom: Medicines and Healthcare Products Regulatory Agency United Kingdom: Research Ethics Committee

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