Trial Outcomes & Findings for A Randomized, Comparative, Open-label Study of IV Monofer® Administered as Maintenance Therapy by Single or Repeated Bolus Injections in Comparison With IV Iron Sucrose in Subjects With CKD-5D (NCT NCT01222884)

Last Updated: 2015-12-02

Results Overview

The primary outcome measure was the proportion of subjects who were able to maintain haemoglobin between 9.5 and 12.5 g/dL (both values included) at week 6. Haemoglobin was measured by a blood sample at the different visits. All blood samples were taken before the dialysis from the dialysis catheter. Intravenous iron was administered during dialysis, at least 30 min after the start and at least 1 h before the end of dialysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

351 participants

Primary outcome timeframe

Baseline to 6 weeks

Results posted on

2015-12-02

Participant Flow

Participant milestones

Participant milestones
Measure	Iron Isomaltoside 1000 Iron isomaltoside 1000 (Monofer)administered as 500 mg intravenous single bolus injections OR administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Monofer: Iron isomaltoside 1000 (Monofer®) administered as 500 mg intravenous single bolus injection over approximately 2 minutes	Iron Sucrose Iron sucrose administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Iron sucrose: Iron sucrose is administered undiluted in doses of 100mg at baseline, 200mg at week 2 and 200 mg at week 4 as fractionated IV bolus injections according to local Summary of Product Characteristics
Overall Study STARTED	234	117
Overall Study COMPLETED	210	113
Overall Study NOT COMPLETED	24	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized, Comparative, Open-label Study of IV Monofer® Administered as Maintenance Therapy by Single or Repeated Bolus Injections in Comparison With IV Iron Sucrose in Subjects With CKD-5D

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Iron Isomaltoside 1000 n=234 Participants Iron isomaltoside 1000 (Monofer)administered as 500 mg intravenous single bolus injections OR administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Monofer: Iron isomaltoside 1000 (Monofer®) administered as 500 mg intravenous single bolus injection over approximately 2 minutes	Iron Sucrose n=117 Participants Iron sucrose administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Iron sucrose: Iron sucrose is administered undiluted in doses of 100mg at baseline, 200mg at week 2 and 200 mg at week 4 as fractionated IV bolus injections according to local Summary of Product Characteristics	Total n=351 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	129 Participants n=5 Participants	66 Participants n=7 Participants	195 Participants n=5 Participants
Age, Categorical >=65 years	105 Participants n=5 Participants	51 Participants n=7 Participants	156 Participants n=5 Participants
Age, Continuous	60.2 years STANDARD_DEVIATION 16.2 • n=5 Participants	59.5 years STANDARD_DEVIATION 15.4 • n=7 Participants	60.0 years STANDARD_DEVIATION 15.9 • n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	43 Participants n=7 Participants	119 Participants n=5 Participants
Sex: Female, Male Male	158 Participants n=5 Participants	74 Participants n=7 Participants	232 Participants n=5 Participants
Region of Enrollment India	44 participants n=5 Participants	28 participants n=7 Participants	72 participants n=5 Participants
Region of Enrollment United Kingdom	131 participants n=5 Participants	56 participants n=7 Participants	187 participants n=5 Participants
Region of Enrollment Russian Federation	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Poland	10 participants n=5 Participants	3 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Sweden	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Switzerland	13 participants n=5 Participants	6 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Romania	14 participants n=5 Participants	12 participants n=7 Participants	26 participants n=5 Participants
Region of Enrollment Denmark	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 6 weeks

Population: The FAS population included all subjects who were randomised into the study, received at least one dose of the study drug, and had a Hb assessment. Subjects were included as randomised, regardless of which treatment they actually received.

Outcome measures

Outcome measures
Measure	Iron Isomaltoside 1000 n=226 Participants Iron isomaltoside 1000 (Monofer)administered as 500 mg intravenous single bolus injections OR administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Monofer: Iron isomaltoside 1000 (Monofer®) administered as 500 mg intravenous single bolus injection over approximately 2 minutes	Iron Sucrose n=115 Participants Iron sucrose administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Iron sucrose: Iron sucrose is administered undiluted in doses of 100mg at baseline, 200mg at week 2 and 200 mg at week 4 as fractionated IV bolus injections according to local Summary of Product Characteristics
Ability to Maintain Hemoglobin Level	82.7 percentage of participants	82.6 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks

Outcome measures

Outcome measures
Measure	Iron Isomaltoside 1000 n=216 Participants Iron isomaltoside 1000 (Monofer)administered as 500 mg intravenous single bolus injections OR administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Monofer: Iron isomaltoside 1000 (Monofer®) administered as 500 mg intravenous single bolus injection over approximately 2 minutes	Iron Sucrose n=113 Participants Iron sucrose administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Iron sucrose: Iron sucrose is administered undiluted in doses of 100mg at baseline, 200mg at week 2 and 200 mg at week 4 as fractionated IV bolus injections according to local Summary of Product Characteristics
Change in Hemoglobin Concentration	-0.07 g/dL Interval -5.5 to 2.9	-0.06 g/dL Interval -4.9 to 2.8

Adverse Events

Iron Isomaltoside 1000

Serious events: 22 serious events

Other events: 42 other events

Deaths: 0 deaths

Iron Sucrose

Serious events: 6 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Iron Isomaltoside 1000 n=230 participants at risk Iron isomaltoside 1000 (Monofer)administered as 500 mg intravenous single bolus injections OR administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Monofer: Iron isomaltoside 1000 (Monofer®) administered as 500 mg intravenous single bolus injection over approximately 2 minutes	Iron Sucrose n=114 participants at risk Iron sucrose administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Iron sucrose: Iron sucrose is administered undiluted in doses of 100mg at baseline, 200mg at week 2 and 200 mg at week 4 as fractionated IV bolus injections according to local Summary of Product Characteristics
Gastrointestinal disorders diarrhoea	2.2% 5/230 • Number of events 5 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	1.8% 2/114 • Number of events 2 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Infections and infestations nasopharyngitis	2.6% 6/230 • Number of events 6 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Infections and infestations lower respiratory tract infection	1.7% 4/230 • Number of events 5 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	2.6% 3/114 • Number of events 4 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Injury, poisoning and procedural complications fall	3.0% 7/230 • Number of events 7 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Injury, poisoning and procedural complications procedural hypotension	2.2% 5/230 • Number of events 18 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 2 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Investigations C-reactive protein increased	2.6% 6/230 • Number of events 6 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Metabolism and nutrition disorders hyperphosphataemia	2.2% 5/230 • Number of events 5 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	3.5% 4/114 • Number of events 4 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Musculoskeletal and connective tissue disorders pain in extremity	2.2% 5/230 • Number of events 6 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Nervous system disorders headache	3.0% 7/230 • Number of events 7 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	3.5% 4/114 • Number of events 5 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population

Additional Information

Vice President Research & Development Department

Pharmacosmos A/S

Phone: +45 59485959

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If Pharmacosmos or its agents has not prepared a draft for submission to a peer reviewed journal prior to 1 year following completion of the study report, the investigators have the right to publish the results. Such publications are to be submitted to Pharmacosmos for comment 30 days prior to submission for publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Iron Isomaltoside 1000 n=230 participants at risk Iron isomaltoside 1000 (Monofer)administered as 500 mg intravenous single bolus injections OR administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Monofer: Iron isomaltoside 1000 (Monofer®) administered as 500 mg intravenous single bolus injection over approximately 2 minutes	Iron Sucrose n=114 participants at risk Iron sucrose administered as 500 mg fractionated (100mg+200mg+200mg) intravenous bolus injection Iron sucrose: Iron sucrose is administered undiluted in doses of 100mg at baseline, 200mg at week 2 and 200 mg at week 4 as fractionated IV bolus injections according to local Summary of Product Characteristics
Cardiac disorders acute coronary syndrome	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Cardiac disorders acute myocardial infarction	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Gastrointestinal disorders duodenal ulcer haemorrhage	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Gastrointestinal disorders gingivalbleeding	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Gastrointestinal disorders lower gastrointestinal haemorrhage	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
General disorders puncture site haemorrhage	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
General disorders sudden death	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Hepatobiliary disorders biliary colic	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Immune system disorders hypersensitivity	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Infections and infestations arteriovenous fistula site infection	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Infections and infestations device related infection	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Infections and infestations infected fistula	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Infections and infestations lower respiratory tract infection	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Infections and infestations respiratory tract infection	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Infections and infestations staphylococcol bacteraimia	0.00% 0/230 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Injury, poisoning and procedural complications fall	1.3% 3/230 • Number of events 3 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Injury, poisoning and procedural complications arteriovenous fistula site haemorrhage	0.87% 2/230 • Number of events 2 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Injury, poisoning and procedural complications femoral neck fracture	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Injury, poisoning and procedural complications vascular graft occlusion	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Injury, poisoning and procedural complications anaesthetic complication	0.00% 0/230 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Injury, poisoning and procedural complications road traffic accident	0.00% 0/230 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Metabolism and nutrition disorders fluid overload	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Musculoskeletal and connective tissue disorders musculoskeletal pain	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Nervous system disorders brain stem infarction	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Renal and urinary disorders nephrolithiasis	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Reproductive system and breast disorders prostatitis	0.00% 0/230 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Respiratory, thoracic and mediastinal disorders dyspnoea	0.00% 0/230 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.88% 1/114 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population
Vascular disorders aortic stenosis	0.43% 1/230 • Number of events 1 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population	0.00% 0/114 The safety population included all subjects who were randomised and received at least one dose of iron isomaltoside 1000 or iron sulphate. The safety analyses was performed on the safety population