Trial Outcomes & Findings for Efficacy and Safety of Peginesatide (AF37702) in the Treatment of Anemia in Participants With Chronic Kidney Disease (NCT NCT00314795)

Last Updated: 2019-03-14

Results Overview

Percentage of participants who experienced increase and maintain hemoglobin levels (two consecutive values) greater than or equal to the lower limit (11 g/dL) in the absence of red blood cell transfusion in the previous 28 days by week 24 were reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Up to Week 24

Results posted on

2019-03-14

Participant Flow

Participants took part in the study at 5 investigative sites in Europe from 06-Apr-2006 to 31-Oct-2016.

Participants with a diagnosis of chronic renal failure (CRF) with confirmed antibody-mediated pure red cell aplasia (PRCA) were enrolled to receive peginesatide subcutaneous injection up to 0.3 mg/kg, once every 4 weeks for up to 60 months.

Participant milestones

Participant milestones
Measure	Peginesatide Peginesatide 0.05 mg/kg injection, subcutaneously followed by peginesatide 0.1 mg/kg injection, subcutaneously once every 4 weeks for up to 60 months. Individual dose of peginesatide injection was modified based on hemoglobin levels. Dose adjustments were made in order to achieve and maintain hemoglobin in the target range of 10.0-12.0 g/dL.
Overall Study STARTED	22
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Peginesatide Peginesatide 0.05 mg/kg injection, subcutaneously followed by peginesatide 0.1 mg/kg injection, subcutaneously once every 4 weeks for up to 60 months. Individual dose of peginesatide injection was modified based on hemoglobin levels. Dose adjustments were made in order to achieve and maintain hemoglobin in the target range of 10.0-12.0 g/dL.
Overall Study Adverse Event	8
Overall Study Death	4
Overall Study Reason not Specified	3
Overall Study Renal Transplant	3
Overall Study Participants Withdrew Consent	2

Baseline Characteristics

Here, number analyzed are the participants who were evaluated for this baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Peginesatide n=22 Participants Peginesatide 0.05 mg/kg injection, subcutaneously followed by peginesatide 0.1 mg/kg injection, subcutaneously once every 4 weeks for up to 60 months. Individual dose of peginesatide injection was modified based on hemoglobin levels. Dose adjustments were made in order to achieve and maintain hemoglobin in the target range of 10.0-12.0 g/dL.
Age, Continuous	73.3 years STANDARD_DEVIATION 13.65 • n=22 Participants
Sex: Female, Male Female	5 Participants n=22 Participants
Sex: Female, Male Male	17 Participants n=22 Participants
Race/Ethnicity, Customized Asian	4 Participants n=22 Participants
Race/Ethnicity, Customized Caucasian	17 Participants n=22 Participants
Race/Ethnicity, Customized Other	1 Participants n=22 Participants
Region of Enrollment France	6 Participants n=22 Participants
Region of Enrollment Germany	8 Participants n=22 Participants
Region of Enrollment United Kingdom	8 Participants n=22 Participants
Height	168.1 cm STANDARD_DEVIATION 9.66 • n=21 Participants • Here, number analyzed are the participants who were evaluated for this baseline measure.
Weight	67.6 kg STANDARD_DEVIATION 12.31 • n=22 Participants
Body Mass Index (BMI)	23.8 kg/m^2 STANDARD_DEVIATION 2.41 • n=21 Participants • Here, number analyzed are the participants who were evaluated for this baseline measure.
Baseline Hemoglobin (Hgb)	96.5 g/L STANDARD_DEVIATION 16.11 • n=22 Participants
Baseline Ferritin	2332.0 ug/L STANDARD_DEVIATION 1695.02 • n=21 Participants • Here, number analyzed are the participants who were evaluated for this baseline measure.
Baseline Transferrin Saturation	79.2 % transferrin STANDARD_DEVIATION 21.87 • n=19 Participants • Here, number analyzed are the participants who were evaluated for this baseline measure.
Baseline Anti-erythropoietin (EPO) Antibody Titers	94.1 U/mL STANDARD_DEVIATION 217.08 • n=22 Participants
Bone Marrow Evaluation Aplasia of Erythropoese	1 Participants n=22 Participants
Bone Marrow Evaluation Erythroblastopenia (EBP)	1 Participants n=22 Participants
Bone Marrow Evaluation EBP 0% normal values for other cell lineages	1 Participants n=22 Participants
Bone Marrow Evaluation Erythroid series absent	1 Participants n=22 Participants
Bone Marrow Evaluation Erythroid severe HYP no decrease in other lineages	1 Participants n=22 Participants
Bone Marrow Evaluation Erythropoietic hypoplasia	1 Participants n=22 Participants
Bone Marrow Evaluation Hpc BM with reduced EL consistent with dgn of pure	1 Participants n=22 Participants
Bone Marrow Evaluation HYP of erythropoiesis staining of iron in BM retic	1 Participants n=22 Participants
Bone Marrow Evaluation Normal	1 Participants n=22 Participants
Bone Marrow Evaluation PRCA	8 Participants n=22 Participants
Bone Marrow Evaluation PRCA / Bone Marrow Trephine	1 Participants n=22 Participants
Bone Marrow Evaluation Pure Red Cell Aplasia	2 Participants n=22 Participants
Bone Marrow Evaluation Red cell aplasia	1 Participants n=22 Participants
Bone Marrow Evaluation Red cell hypoplasia	1 Participants n=22 Participants

PRIMARY outcome

Timeframe: Up to Week 24

Population: Efficacy endpoint data was not collected due to low patient enrollment and the drug was withdrawn from the market.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 26 weeks prior to enrollment up to end of study (up to 60 months)

Population: Efficacy endpoint data was not collected due to low patient enrollment and the drug was withdrawn from the market.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 26 weeks prior to enrollment up to end of study (up to 60 months)

Population: Efficacy endpoint data was not collected due to low patient enrollment and the drug was withdrawn from the market.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 60 months

Population: Efficacy endpoint data was not collected due to low patient enrollment and the drug was withdrawn from the market.

The time between first dose administered and the initial achievement of a Hgb increase ≥11 g/dL for two consecutive visits was calculated for each participant as the number of days between the first dose administration date and the earlier of (1) the study termination date \[i.e. censor date\] and (2) the first date of an Hgb increase ≥ 11 g/dL for two consecutive visits without whole blood or RBC transfusion during the previous 28 days. Time to initial Hgb increase ≥ 11 g/dL will be calculated for each participant as the minimum of censor date and increase date minus the first dose date plus 1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From signing of informed consent form up to Month 60

Population: Safety analysis set included all participants who received at least one dose of study drug.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Outcome measures

Outcome measures
Measure	Peginesatide n=22 Participants Peginesatide 0.05 mg/kg injection, subcutaneously followed by peginesatide 0.1 mg/kg injection, subcutaneously once every 4 weeks for up to 60 months. Individual dose of peginesatide injection was modified based on hemoglobin levels. Dose adjustments were made in order to achieve and maintain hemoglobin in the target range of 10.0-12.0 g/dL.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation SAEs	17 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation AEs Leading to Study Drug Discontinuation	3 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation AEs	22 Participants

Adverse Events

Peginesatide

Serious events: 17 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Peginesatide n=22 participants at risk Peginesatide 0.05 mg/kg injection, subcutaneously followed by peginesatide 0.1 mg/kg injection, subcutaneously once every 4 weeks for up to 60 months. Individual dose of peginesatide injection was modified based on hemoglobin levels. Dose adjustments were made in order to achieve and maintain hemoglobin in the target range of 10.0-12.0 g/dL.
Blood and lymphatic system disorders Anaemia	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Blood and lymphatic system disorders Neutropenia	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Acute myocardial infarction	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Angina pectoris	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Atrial fibrillation	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Atrial flutter	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Atrioventricular block	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Atrioventricular block complete	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Cardiac arrest	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Cardiac failure	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Cardiac failure acute	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Myocardial infarction	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Eye disorders Optic ischaemic neuropathy	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Gastrointestinal disorders Anal prolapse	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
General disorders Chest Pain	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
General disorders Death	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
General disorders Sudden death	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
General disorders Vascular stent restenosis	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Cytomegalovirus infection	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Disseminated tuberculosis	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Endocarditis	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Escherichia bacteraemia	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Gangrene	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Lower respiratory tract infection	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Pneumocystis jirovecii pneumonia	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Pneumonia	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Urinary tract infection	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Urosepsis	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Femur fracture	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Coronary artery restenosis	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Peritoneal dialysis complication	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Shunt occlusion	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Investigations C-reactive protein increased	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Investigations Drug specific antibody present	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Investigations Haematocrit decreased	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Metabolism and nutrition disorders Fluid overload	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Metabolism and nutrition disorders Hyperkalaemia	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal cancer metastatic	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer recurrent	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Nervous system disorders Vascular dementia	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Renal and urinary disorders Renal salt-wasting syndrome	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Vascular disorders Aortic stenosis	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Vascular disorders Blood pressure inadequately controlled	4.5% 1/22 • From signing of informed consent form up to Month 60 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.
Vascular disorders Femoral artery aneurysm	4.5% 1/22 • From signing of informed consent form up to Month 60 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.

Other adverse events

Other adverse events
Measure	Peginesatide n=22 participants at risk Peginesatide 0.05 mg/kg injection, subcutaneously followed by peginesatide 0.1 mg/kg injection, subcutaneously once every 4 weeks for up to 60 months. Individual dose of peginesatide injection was modified based on hemoglobin levels. Dose adjustments were made in order to achieve and maintain hemoglobin in the target range of 10.0-12.0 g/dL.
Musculoskeletal and connective tissue disorders Osteoarthritis	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Cardiac disorders Palpitations	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Ear and labyrinth disorders Tinnitus	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Eye disorders Cataract	18.2% 4/22 • From signing of informed consent form up to Month 60 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.
Gastrointestinal disorders Diarrhoea	45.5% 10/22 • From signing of informed consent form up to Month 60 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.
Gastrointestinal disorders Constipation	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Gastrointestinal disorders Toothache	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Gastrointestinal disorders Vomitting	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Gastrointestinal disorders Nausea	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
General disorders Oedema peripheral	31.8% 7/22 • From signing of informed consent form up to Month 60 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.
General disorders Asthenia	27.3% 6/22 • From signing of informed consent form up to Month 60 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.
General disorders Fatigue	22.7% 5/22 • From signing of informed consent form up to Month 60 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.
General disorders Non-cardiac chest pain	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
General disorders Pyrexia	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Hepatobiliary disorders Hepatomegaly	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Immune system disorders Drug hypersensitivity	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Immune system disorders Seasonal allergy	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Nasopharyngitis	45.5% 10/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Bronchitis	27.3% 6/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Urinary tract infection	27.3% 6/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Upper respiratory tract infection	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Cystitis	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Cytomegalovirus infection	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Lower respiratory tract infection	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Infections and infestations Respiratory tract infection	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Fall	36.4% 8/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Skin abrasion	22.7% 5/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Contusion	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Heat exhaustion	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Injury, poisoning and procedural complications Procedural hypotension	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Investigations Haemoglobin decreased	27.3% 6/22 • From signing of informed consent form up to Month 60 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.
Investigations Weight decreased	18.2% 4/22 • From signing of informed consent form up to Month 60 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.
Investigations Blood pressure increased	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Investigations Blood phosphorus increased	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Investigations Blood potassium increased	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Investigations Liver function test increased	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Investigations Platelet count decreased	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Investigations Reticulocyte count decreased	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Metabolism and nutrition disorders Decreased appetite	18.2% 4/22 • From signing of informed consent form up to Month 60 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.
Metabolism and nutrition disorders Fluid overload	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Musculoskeletal and connective tissue disorders Arthralgia	22.7% 5/22 • From signing of informed consent form up to Month 60 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.
Musculoskeletal and connective tissue disorders Back pain	22.7% 5/22 • From signing of informed consent form up to Month 60 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.
Musculoskeletal and connective tissue disorders Muscke spasms	22.7% 5/22 • From signing of informed consent form up to Month 60 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Nervous system disorders Dizziness	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Nervous system disorders Headache	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Nervous system disorders Restless legs syndrome	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Nervous system disorders Sciatica	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Renal and urinary disorders Haematuria	18.2% 4/22 • From signing of informed consent form up to Month 60 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.
Renal and urinary disorders Chronic kidney disease	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Respiratory, thoracic and mediastinal disorders Cough	22.7% 5/22 • From signing of informed consent form up to Month 60 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Respiratory, thoracic and mediastinal disorders Rales	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Skin and subcutaneous tissue disorders Eczema	18.2% 4/22 • From signing of informed consent form up to Month 60 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.
Skin and subcutaneous tissue disorders Pruritus Generalised	9.1% 2/22 • From signing of informed consent form up to Month 60 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.
Vascular disorders Hypertension	27.3% 6/22 • From signing of informed consent form up to Month 60 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.
Vascular disorders Haematoma	13.6% 3/22 • From signing of informed consent form up to Month 60 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.
Vascular disorders Hypotension	13.6% 3/22 • From signing of informed consent form up to Month 60 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER