A Study of Intravenous Iron Isomaltoside 1000 (Monofer®) as Mono Therapy (Without Erythropoiesis Stimulating Agents) in Comparison With Oral Iron Sulfate in Subjects With Non-myeloid Malignancies Associated With Chemotherapy Induced Anaemia (CIA)

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ClinicalTrials.gov Identifier: NCT01145638

Recruitment Status : Completed

First Posted : June 16, 2010

Results First Posted : December 3, 2015

Last Update Posted : December 3, 2015

Sponsor:

Information provided by (Responsible Party):

Pharmacosmos A/S

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Non-myeloid Malignancies Chemotherapy Induced Anaemia
Interventions	Drug: iron isomaltoside 1000 Drug: iron sulphate
Enrollment	350

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Iron Isomaltoside 1000	Iron Sulphate
Arm/Group Description	Iron isomaltoside intravenously as ...	oral iron sulphate twice a day ...
Arm/Group Description	Iron isomaltoside intravenously as bolus or infusion iron isomaltoside 1000: intravenously as bolus or infusion, 500 mg or 1000mg up to full replacement dose	oral iron sulphate twice a day iron sulphate: oral, 200 mg per day (100 mg bid),12 weeks
Period Title: Overall Study
Started	231	119
Completed	141	62
Not Completed	90	57

Baseline Characteristics

Arm/Group Title		Iron Isomaltoside 1000	Iron Sulphate	Total
Arm/Group Description		Iron isomaltoside intravenously as ...	oral iron sulphate twice a day ...	Total of all reporting groups
Arm/Group Description		Iron isomaltoside intravenously as bolus or infusion iron isomaltoside 1000: intravenously as bolus or infusion, 500 mg or 1000mg up to full replacement dose	oral iron sulphate twice a day iron sulphate: oral, 200 mg per day (100 mg bid),12 weeks	Total of all reporting groups
Overall Number of Baseline Participants		231	119	350
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	231 participants	119 participants	350 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	187 81.0%	101 84.9%	288 82.3%
	>=65 years	44 19.0%	18 15.1%	62 17.7%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	231 participants	119 participants	350 participants
	Female	151 65.4%	90 75.6%	241 68.9%
	Male	80 34.6%	29 24.4%	109 31.1%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	231 participants	119 participants	350 participants
India		133	72	205
Germany		7	3	10
Denmark		3	1	4
Spain		2	0	2
Poland		40	16	56
Russian Federation		29	18	47
Sweden		5	3	8
United States		12	6	18

Outcome Measures

1.Primary Outcome


Title	Change in Hb Concentration
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline week 4

Outcome Measure Data

Analysis Population Description

The FAS population included all the subjects who were randomised into the study, received at least one dose of the study drug, and had at least one post-baseline Hb assessment. The subjects were considered as randomised, regardless of which treatment they actually received.


Arm/Group Title	Iron Isomaltoside 1000	Iron Sulphate
Arm/Group Description:	Iron isomaltoside intravenously as ...	oral iron sulphate twice a day ...
Arm/Group Description:	Iron isomaltoside intravenously as bolus or infusion iron isomaltoside 1000: intravenously as bolus or infusion, 500 mg or 1000mg up to full replacement dose	oral iron sulphate twice a day iron sulphate: oral, 200 mg per day (100 mg bid),12 weeks
Overall Number of Participants Analyzed	192	99
Mean (Full Range) Unit of Measure: g/dL
	0.48 (-4 to 4)	0.44 (-2 to 4)

2.Secondary Outcome


Title	Change in Hemoglobin From Baseline to Week 24
Description	[Not Specified]
Description	[Not Specified]
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Iron Isomaltoside 1000	Iron Sulphate
Arm/Group Description:	Iron isomaltoside intravenously as ...	oral iron sulphate twice a day ...
Arm/Group Description:	Iron isomaltoside intravenously as bolus or infusion iron isomaltoside 1000: intravenously as bolus or infusion, 500 mg or 1000mg up to full replacement dose	oral iron sulphate twice a day iron sulphate: oral, 200 mg per day (100 mg bid),12 weeks
Overall Number of Participants Analyzed	157	72
Mean (Full Range) Unit of Measure: g/dL
	1.60 (-6.3 to 6.5)	1.78 (-5.3 to 7.4)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	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.

Arm/Group Title	Iron Isomaltoside 1000		Iron Sulphate
Arm/Group Description	Iron isomaltoside intravenously as ...		oral iron sulphate twice a day ...
Arm/Group Description	Iron isomaltoside intravenously as bolus or infusion iron isomaltoside 1000: intravenously as bolus or infusion, 500 mg or 1000mg up to full replacement dose		oral iron sulphate twice a day iron sulphate: oral, 200 mg per day (100 mg bid),12 weeks
All-Cause Mortality
	Iron Isomaltoside 1000		Iron Sulphate
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Iron Isomaltoside 1000		Iron Sulphate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/229 (13.97%)		18/112 (16.07%)
Blood and lymphatic system disorders
Anaemia ^†	2/229 (0.87%)	2	2/112 (1.79%)	2
Neutropenia ^†	2/229 (0.87%)	2	0/112 (0.00%)	0
Pancytopenia ^†	1/229 (0.44%)	1	1/112 (0.89%)	1
Cardiac disorders
Atrial fibrillation ^†	3/229 (1.31%)	3	1/112 (0.89%)	1
Cardiac failure ^†	1/229 (0.44%)	1	1/112 (0.89%)	1
Gastrointestinal disorders
Abdominal pain ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Ascites ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Gastrointestinal haemorrhage ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Gastrointestinal polyp haemorrhage ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Mouth haemorrhage ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Stomatitis ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
General disorders
Asthenia ^†	1/229 (0.44%)	1	1/112 (0.89%)	1
Sudden death ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Immune system disorders
Anaphylactic reaction ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Infections and infestations
Pneumonia ^†	2/229 (0.87%)	2	0/112 (0.00%)	0
Sepsis ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Unirary tract infection ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Injury, poisoning and procedural complications
Post procedural complication ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Investigations
Electrocardiogram abnormal ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Haemoglobin decreased ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Metabolism and nutrition disorders
Dehydration ^†	2/229 (0.87%)	2	0/112 (0.00%)	0
Hyperglycaemia ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Hypoglycaemia ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Hyponatraemia ^†	2/229 (0.87%)	2	0/112 (0.00%)	0
Musculoskeletal and connective tissue disorders
Fistula ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression ^†	8/229 (3.49%)	9	7/112 (6.25%)	7
Malignant pleural effusion ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Metastases to lung ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Metastases to meninges ^†	0/229 (0.00%)	0	1/112 (0.89%)	2
Nervous system disorders
Convulsion ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Headache ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Transient ischaemic attack ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Dyspnoe ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Epistaxis ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Pneumonia aspiration ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
Pneumothorax ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Respiratory distress ^†	0/229 (0.00%)	0	1/112 (0.89%)	1
Stridor ^†	1/229 (0.44%)	1	0/112 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Iron Isomaltoside 1000		Iron Sulphate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	173/229 (75.55%)		107/112 (95.54%)
Blood and lymphatic system disorders
Anaemia ^†	20/229 (8.73%)	22	12/112 (10.71%)	13
Leukopenia ^†	12/229 (5.24%)	13	10/112 (8.93%)	13
Neutropenia ^†	15/229 (6.55%)	21	6/112 (5.36%)	9
Thrombocytopenia ^†	11/229 (4.80%)	13	7/112 (6.25%)	11
Gastrointestinal disorders
Constipation ^†	7/229 (3.06%)	8	7/112 (6.25%)	7
Diarrhoea ^†	8/229 (3.49%)	14	10/112 (8.93%)	11
Faeces discoloured ^†	1/229 (0.44%)	1	9/112 (8.04%)	9
Nausea ^†	14/229 (6.11%)	19	8/112 (7.14%)	12
Stomatitis ^†	14/229 (6.11%)	14	5/112 (4.46%)	5
Vomiting ^†	16/229 (6.99%)	24	7/112 (6.25%)	8
General disorders
Asthenia ^†	18/229 (7.86%)	20	7/112 (6.25%)	9
Pyrexia ^†	12/229 (5.24%)	13	4/112 (3.57%)	4
Metabolism and nutrition disorders
Decreased appetite ^†	8/229 (3.49%)	8	6/112 (5.36%)	6
Skin and subcutaneous tissue disorders
Alopecia ^†	17/229 (7.42%)	17	9/112 (8.04%)	9
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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.

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.

Results Point of Contact

Name/Title: Vice President Research & Development Department

Organization: Pharmacosmos A/S

Phone: +45 59485959

EMail: llt@pharmacosmos.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Birgegård G, Henry D, Glaspy J, Chopra R, Thomsen LL, Auerbach M. A Randomized Noninferiority Trial of Intravenous Iron Isomaltoside versus Oral Iron Sulfate in Patients with Nonmyeloid Malignancies and Anemia Receiving Chemotherapy: The PROFOUND Trial. Pharmacotherapy. 2016 Apr;36(4):402-14. doi: 10.1002/phar.1729. Epub 2016 Apr 1.

Responsible Party:	Pharmacosmos A/S
ClinicalTrials.gov Identifier:	NCT01145638 History of Changes
Other Study ID Numbers:	P-Monofer-CIA-01 EudraCT no. 2009-016727-53
First Submitted:	June 15, 2010
First Posted:	June 16, 2010
Results First Submitted:	September 21, 2015
Results First Posted:	December 3, 2015
Last Update Posted:	December 3, 2015

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