A Phase 3, Randomized, Double Blind, Placebo-Controlled, Multi-Center, Withdrawal Study of MCI-196 in CKD on Dialysis With Hyperphosphatemia

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00506441
• Collaborator: (none)
• Enrollment: 245
• Locations: 39
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a phase III multi-centre study in three periods: the first period is a phosphate binder washout for 4 weeks, the second period is an open-label, flexible dose titration, the third period is a placebo-controlled withdrawal comparing MCI-196 with placebo for 4 weeks.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease; Dialysis; Hyperphosphatemia	Drug: MCI-196; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 245 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-center, Withdrawal Study Comparing MCI-196 v.s Placebo Following A 12-Week Dose Titration Period With MCI-196 in Stage V Subjects on Dialysis With Hyperphosphatemia
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: MCI-196; 3g to 15g/day (3 times a day), Tablet, 12 weeks of flexible dose (Open-label) and 4 weeks of double blind; Other Names: Colestilan(INN) Colestimide(JAN) CHOLEBINE® BindRen®
Placebo Comparator: 2	Drug: Placebo; 3g to 15g/day (3 times a day), Tablet, 4 weeks of double blind

Outcome Measures

Primary Outcome Measures

1. The Change in Serum Phosphorus From Week 12 to Week 16 [4 weeks (Week 12 to Week 16)]

   The changes in serum phosphorus (mg/dL) from Week 12 to Week 16 (last observation post Week 12)

Secondary Outcome Measures

1. Change From Baseline in Serum Phosphorus [12 weeks (Week 0 to Week 12)]

2. Change From Baseline in PTH [12 weeks]

3. Change From Baseline in Calcium [12 weeks]

4. Change From Baseline in Calcium x Phosphorus Ion Product [12 weeks]

5. Change From Baseline in Total Cholesterol [12 weeks]

6. Change From Baseline in LDL Cholesterol [12 weeks]

7. Change From Baseline in HDL Cholesterol [12 weeks]

8. Change From Baseline in VLDL Cholesterol [12 weeks]

9. Change From Baseline in Triglyceride [12 weeks]

10. Incidence of Adverse Events [12 weeks (Week 0-12) and 4 weeks (Week 12-16)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, and is >=18 years old

• Stable hemodialysis or peritoneal dialysis

• Subjects has Stable phosphate control

• Subjects on Stabilized phosphorus diet

• Subjects undergoing regular dialysis treatment

• Female and of child-bearing potential have a negative serum pregnancy test.

• Male subjects must agree to use appropriate contraception.

Exclusion Criteria:

• Current clinically significant medical comorbidities, which may substantially compromise subject safety, or expose them to undue risk, or interfere significantly with study procedures and which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study.

• serum albumin level < 3.0g/dL

• PTH level > 1000pg/mL

• Hemoglobin level < 8mg/dL

• A History of significant gastrointestinal motility problems

• Biliary obstruction or proven liver dysfunction

• A positive test for hepatitis B surface antigen, hepatitis C antibody or HIV 1 and 2 antibodies

• A clinically significant severe lactose intolerance or sensitivity

• A history of substance or alcohol abuse within the last year.

• Seizure disorders

• A history of drug or other allergy

• using cholestyramine, colestipol or colesevelam

• Schedule to receive a kidney transplant within the next 6 months

• Participation in a clinical study with any experimental medication in the last 30 days or an experimental biological product within the last 90 days prior to signing of informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Glendale	Arizona	United States
2		Tempe	Arizona	United States
3		Hot Springs	Arkansas	United States
4		Paragould	Arkansas	United States
5		Pine Bluff	Arkansas	United States
6		Fountain Valley	California	United States
7		La Mesa	California	United States
8		Long Beach	California	United States
9		Lynwood	California	United States
10		Orange	California	United States
11		San Diego	California	United States
12		Whittier	California	United States
13		Brandon	Florida	United States
14		Hudson	Florida	United States
15		Lauderdale Lakes	Florida	United States
16		Tampa	Florida	United States
17		Augusta	Georgia	United States
18		Decatur	Georgia	United States
19		Macon	Georgia	United States
20		Evanston	Illinois	United States
21		Evergreen Park	Illinois	United States
22		Fort Wayne	Indiana	United States
23		Shreveport	Louisiana	United States
24		Springfield	Massachusetts	United States
25		Eatontown	New Jersey	United States
26		Flushing	New York	United States
27		Springfield Gardens	New York	United States
28		Allentown	Pennsylvania	United States
29		Lewistown	Pennsylvania	United States
30		Philadelphia	Pennsylvania	United States
31		Columbia	South Carolina	United States
32		Orangeburg	South Carolina	United States
33		Sumter	South Carolina	United States
34		San Antonio	Texas	United States
35		Alexandria	Virginia	United States
36		Portsmouth	Virginia	United States
37		Richmond	Virginia	United States
38		West Allis	Wisconsin	United States
39		San Juan		Puerto Rico

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Principal Investigator: Professor, Information at Mitsubishi Pharma America

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT00506441
• Other Study ID Numbers: MCI-196-A05
• First Posted: Jul 25, 2007
• Last Update Posted: Sep 15, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Mitsubishi Tanabe Pharma Corporation: Chronic Kidney Disease; Dialysis; Hyperphosphatemia; Phosphate binder
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hyperphosphatemia

Study Results

Participant Flow

Arm/Group Title	MCI-196	Placebo
Arm/Group Description	Open-label Period (Week 0 -12) ; 3, 6, 9, 12, or 15 g/ day as titrated Double-blind Period (Week 12 - 16) ; dose level at the end of dose titration in the Open-label period	Double-blind Period (Week 12 - 16) ; dose level at the end of dose titration in the Open-label period
Period Title: Period 1; Open-label Period
STARTED	245	0
COMPLETED	169	0
NOT COMPLETED	76	0
Period Title: Period 1; Open-label Period
STARTED	85	84
COMPLETED	82	79
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	MCI-196
Arm/Group Description	Open-label Period (Week 0 - 12) ; 3, 6, 9, 12, or 15 g/ day as titrated Double-blind Period (Week 12 - 16) ; dose level at the end of dose titration in the Open-label period
Overall Participants	245
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.8 (12.9)
Sex: Female, Male (Count of Participants)
Female	99 40.4%
Male	146 59.6%

Outcome Measures

1. Primary Outcome

Title	The Change in Serum Phosphorus From Week 12 to Week 16
Description	The changes in serum phosphorus (mg/dL) from Week 12 to Week 16 (last observation post Week 12)
Time Frame	4 weeks (Week 12 to Week 16)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) 2 (The ITT2 population included all subjects who complete 12-weeks, receive a randomization number and receive at least one dose of study medication in the placebo-controlled withdrawal phase, either MCI-196 or placebo, and have at least one central phosphorus value after 12-weeks.)

Arm/Group Title	MCI-196 (Double-blind Period)	Placebo (Double-blind Period)
Arm/Group Description	Double-blind Period (Week 12 - 16) ; dose level at the end of dose titration in the Open-label period	Double-blind Period (Week 12 - 16) ; dose level at the end of dose titration in the Open-label period
Measure Participants	85	83
Mean (Standard Deviation) [mg / dL]	-0.04 (1.49)	0.71 (1.71)

2. Secondary Outcome

Title	Change From Baseline in Serum Phosphorus
Time Frame	12 weeks (Week 0 to Week 12)

Outcome Measure Data

Analysis Population Description

ITT1 (The ITT1 population included all enrolled subjects who have taken at least one dose of study medication and have at least one central phosphorus value after the start of study medication.)

Arm/Group Title	MCI-196 (Open-label Period)
Arm/Group Description	3, 6, 9, 12, or 15g/day as titrated (Week 0 -12)
Measure Participants	241
Mean (95% Confidence Interval) [mg/dL]	-1.54

3. Secondary Outcome

Title	Change From Baseline in PTH
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Change From Baseline in Calcium
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Change From Baseline in Calcium x Phosphorus Ion Product
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Change From Baseline in Total Cholesterol
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Change From Baseline in LDL Cholesterol
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Change From Baseline in HDL Cholesterol
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Change From Baseline in VLDL Cholesterol
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Change From Baseline in Triglyceride
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Incidence of Adverse Events
Time Frame	12 weeks (Week 0-12) and 4 weeks (Week 12-16)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	12 weeks (Week 0-12) and 4 weeks (Week 12 - 16)
Adverse Event Reporting Description	Open-label Period is 12 weeks from Week 0 to Week 12. Double-Blind Period is 4 weeks after randomization at Week 12.
Arm/Group Title	MCI-196 (Open-label Period)		MCI-196 (Double-blind Period)		Placebo (Double-blind Period)
Arm/Group Description	3, 6, 9, 12, or 15 g/ day as titrated (Week 0-12)		dose level at the end of dose titration in the Open-label period (Week 12-16) One subject who was randomized to placebo and another subject who was randomized to MCI-196 took both placebo and MCI-196 during the double-blind period. They have therefore been included in the MCI-196 group for the safety evaluation for the double-blind period.		dose level at the end of dose titration in the Open-label period (Week 12-16) One subject who was randomized to placebo and another subject who was randomized to MCI-196 took both placebo and MCI-196 during the double-blind period. They have therefore been included in the MCI-196 group for the safety evaluation for the double-blind period.
All Cause Mortality
	MCI-196 (Open-label Period)		MCI-196 (Double-blind Period)		Placebo (Double-blind Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MCI-196 (Open-label Period)		MCI-196 (Double-blind Period)		Placebo (Double-blind Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/245 (15.1%)		10/86 (11.6%)		7/83 (8.4%)
Blood and lymphatic system disorders
Anaemia	3/245 (1.2%)		0/86 (0%)		1/83 (1.2%)
Coagulopathy	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Cardiac disorders
Angina unstable	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Myocardial infarction	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Atrial fibrillation	2/245 (0.8%)		1/86 (1.2%)		1/83 (1.2%)
Acute myocardial infarction	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Atrioventricular block complete	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Bradycardia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Cardiomyopathy	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Angina pectoris	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Cardiac failure congestive	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Pericarditis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Pericardial effusion	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Cardiac arrest	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Endocrine disorders
Goitre	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Gastrointestinal disorders
Duodenitis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Gastritis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Small intestinal haemorrhage	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Pancreatitis acute	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Nausea	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Vomiting	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Peritoneal haemorrhage	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Peritonitis	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Upper gastrointestinal haemorrhage	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Diverticulitis intestinal haemorrhagic	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Diabetic gastroparesis	0/245 (0%)	0	1/86 (1.2%)	0	0/83 (0%)	0
Enteritis	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
General disorders
Non-cardiac chest pain	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Pyrexia	3/245 (1.2%)		0/86 (0%)		0/83 (0%)
Catheter site haemorrhage	1/245 (0.4%)		0/86 (0%)		1/83 (1.2%)
Chest pain	1/245 (0.4%)		0/86 (0%)		1/83 (1.2%)
Hepatobiliary disorders
Cholelithiasis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Infections and infestations
Sepsis	2/245 (0.8%)		1/86 (1.2%)		0/83 (0%)
Pneumonia	3/245 (1.2%)		2/86 (2.3%)		0/83 (0%)
Subcutaneous abscess	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Cellulitis	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Bronchitis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Arteriovenous graft site infection	1/245 (0.4%)		0/86 (0%)		1/83 (1.2%)
Staphylococcal infection	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Osteomyelitis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Gangrene	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Staphylococcal bacteraemia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Gastroenteritis	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Septic shock	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Urinary tract infection	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Catheter related infection	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Injury, poisoning and procedural complications
Vascular graft complication	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Humerus fracture	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Arteriovenous graft thrombosis	3/245 (1.2%)		0/86 (0%)		0/83 (0%)
In-stent coronary artery restenosis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Vascular graft occlusion	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Arteriovenous fistula occlusion	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Arteriovenous fistula site haemorrhage	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Graft thrombosis	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Investigations
Liver function test abnormal	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Colonoscopy abnormal	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Hyperkalaemia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Diabetes mellitus inadequate control	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Fluid overload	3/245 (1.2%)		0/86 (0%)		0/83 (0%)
Diabetic foot	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Musculoskeletal and connective tissue disorders
Neck pain	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Neuropathic arthropathy	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Metastases to liver	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Nervous system disorders
Transient ischaemic attack	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Syncope	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Haemorrhagic stroke	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Psychiatric disorders
Delirium	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Renal and urinary disorders
Hydronephrosis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Renal cyst	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Dyspnoea	1/245 (0.4%)		1/86 (1.2%)		0/83 (0%)
Acute respiratory failure	1/245 (0.4%)		1/86 (1.2%)		0/83 (0%)
Chronic obstructive pulmonary disease	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Tracheal stenosis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Pulmonary oedema	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Asthma	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Wheezing	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Hypoxia	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Vascular disorders
Hypertension	3/245 (1.2%)		1/86 (1.2%)		0/83 (0%)
Hypotension	3/245 (1.2%)		0/86 (0%)		1/83 (1.2%)
Shock haemorrhagic	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Superior vena caval occlusion	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Accelerated hypertension	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Other (Not Including Serious) Adverse Events
	MCI-196 (Open-label Period)		MCI-196 (Double-blind Period)		Placebo (Double-blind Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	161/245 (65.7%)		34/86 (39.5%)		25/83 (30.1%)
Blood and lymphatic system disorders
Thrombocytopenia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Anaemia	1/245 (0.4%)		1/86 (1.2%)		0/83 (0%)
Haemorrhagic anaemia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Cardiac disorders
Cardiac failure acute	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Sinus tachycardia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Atrial fibrillation	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Cardiac failure congestive	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Conduction disorder	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Bradycardia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Cardiomegaly	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Bundle branch block	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Myocardial ischaemia	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Bundle branch block right	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Tachycardia	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Ear and labyrinth disorders
Hypoacusis	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Ear pain	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Endocrine disorders
Hypothyroidism	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Hyperparathyroidism secondary	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Eye disorders
Vision blurred	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Conjunctivitis	3/245 (1.2%)		1/86 (1.2%)		0/83 (0%)
Visual impairment	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Lacrimation increased	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Cataract	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Eye haemorrhage	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Ocular hyperaemia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Eye swelling	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Gastrointestinal disorders
Nausea	21/245 (8.6%)		4/86 (4.7%)		0/83 (0%)
Diarrhoea	22/245 (9%)		3/86 (3.5%)		3/83 (3.6%)
Abdominal pain	5/245 (2%)		0/86 (0%)		0/83 (0%)
Diverticulum	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Melaena	1/245 (0.4%)		1/86 (1.2%)		0/83 (0%)
Dyspepsia	12/245 (4.9%)		0/86 (0%)		0/83 (0%)
Vomiting	18/245 (7.3%)		3/86 (3.5%)		0/83 (0%)
Abdominal discomfort	4/245 (1.6%)		1/86 (1.2%)		0/83 (0%)
Abdominal distension	5/245 (2%)		0/86 (0%)		0/83 (0%)
Hiatus hernia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Constipation	15/245 (6.1%)		1/86 (1.2%)		0/83 (0%)
Gastrooesophageal reflux disease	3/245 (1.2%)		0/86 (0%)		0/83 (0%)
Abdominal pain upper	4/245 (1.6%)		0/86 (0%)		1/83 (1.2%)
Dry mouth	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Hyperchlorhydria	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Flatulence	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Abdominal mass	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Peritonitis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Tooth disorder	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Haemorrhoids	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Abdominal pain	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Lip pain	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
General disorders
Chills	3/245 (1.2%)		0/86 (0%)		0/83 (0%)
Malaise	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Oedema peripheral	6/245 (2.4%)		3/86 (3.5%)		1/83 (1.2%)
Chest pain	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Pyrexia	6/245 (2.4%)		1/86 (1.2%)		0/83 (0%)
Asthenia	7/245 (2.9%)		0/86 (0%)		0/83 (0%)
Fatigue	4/245 (1.6%)		2/86 (2.3%)		0/83 (0%)
Gait disturbance	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Generalised oedema	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Oedema	4/245 (1.6%)		2/86 (2.3%)		1/83 (1.2%)
Influenza like illness	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Tenderness	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Face oedema	3/245 (1.2%)		0/86 (0%)		0/83 (0%)
Hepatobiliary disorders
Cholelithiasis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Immune system disorders
Drug hypersensitivity	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Seasonal allergy	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Infections and infestations
Diverticulitis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Urinary tract infection	6/245 (2.4%)		0/86 (0%)		3/83 (3.6%)
Influenza	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Cellulitis	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Hordeolum	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Nasopharyngitis	4/245 (1.6%)		1/86 (1.2%)		2/83 (2.4%)
Tooth infection	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Upper respiratory tract infection	9/245 (3.7%)		0/86 (0%)		0/83 (0%)
Gastroenteritis	1/245 (0.4%)		1/86 (1.2%)		0/83 (0%)
Bronchitis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Staphylococcal sepsis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Ear infection	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Lymphangitis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Lower respiratory tract infection	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Infection	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Arteriovenous fistula site infection	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Hepatitis C	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Fungal infection	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Localised infection	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Eyelid infection	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Infected skin ulcer	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Arteriovenous graft site infection	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Eye infection	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula site haematoma	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Arteriovenous fistula site complication	11/245 (4.5%)		1/86 (1.2%)		1/83 (1.2%)
Limb injury	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Fall	2/245 (0.8%)		1/86 (1.2%)		0/83 (0%)
Arteriovenous fistula thrombosis	3/245 (1.2%)		1/86 (1.2%)		1/83 (1.2%)
Arteriovenous graft thrombosis	6/245 (2.4%)		0/86 (0%)		0/83 (0%)
Vascular graft complication	2/245 (0.8%)		0/86 (0%)		2/83 (2.4%)
Rib fracture	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Vascular access complication	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Arteriovenous fistula site haemorrhage	1/245 (0.4%)		1/86 (1.2%)		0/83 (0%)
Haemodialysis-induced symptom	5/245 (2%)		1/86 (1.2%)		1/83 (1.2%)
Procedural hypotension	1/245 (0.4%)		0/86 (0%)		1/83 (1.2%)
Procedural pain	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Excoriation	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Muscle strain	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Arteriovenous graft site haemorrhage	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Graft haemorrhage	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Procedural hypertension	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Investigations
Blood phosphorus increased	4/245 (1.6%)		0/86 (0%)		0/83 (0%)
Blood phosphorus decreased	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Electrocardiogram QT prolonged	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Body temperature increased	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Prothrombin time prolonged	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Weight decreased	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Blood triglycerides increased	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Carbon dioxide decreased	2/245 (0.8%)		0/86 (0%)		1/83 (1.2%)
High density lipoprotein decreased	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Urine output decreased	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Very low density lipoprotein increased	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Vitamin D decreased	1/245 (0.4%)		0/86 (0%)		1/83 (1.2%)
Blood alkaline phosphatase increased	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Blood calcium decreased	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Blood parathyroid hormone increased	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Cardiac murmur	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Gamma-glutamyltransferase increased	0/245 (0%)		1/86 (1.2%)		1/83 (1.2%)
Osteocalcin increased	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Metabolism and nutrition disorders
Iron deficiency	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Decreased appetite	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Hypocalcaemia	6/245 (2.4%)		0/86 (0%)		0/83 (0%)
Hyperkalaemia	2/245 (0.8%)		1/86 (1.2%)		0/83 (0%)
Fluid overload	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Metabolic acidosis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Hypercalcaemia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Calcium deficiency	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Hypoglycaemia	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Hypokalaemia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Folate deficiency	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Vitamin D deficiency	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Dehydration	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Musculoskeletal and connective tissue disorders
Back pain	11/245 (4.5%)		0/86 (0%)		0/83 (0%)
Muscular weakness	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Pain in extremity	8/245 (3.3%)		1/86 (1.2%)		1/83 (1.2%)
Arthralgia	2/245 (0.8%)		3/86 (3.5%)		1/83 (1.2%)
Pain in jaw	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Musculoskeletal chest pain	1/245 (0.4%)		1/86 (1.2%)		1/83 (1.2%)
Musculoskeletal pain	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Muscle spasms	5/245 (2%)		0/86 (0%)		1/83 (1.2%)
Arthritis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Neck pain	3/245 (1.2%)		0/86 (0%)		1/83 (1.2%)
Intervertebral disc protrusion	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Nervous system disorders
Sinus headache	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Headache	10/245 (4.1%)		1/86 (1.2%)		2/83 (2.4%)
Paraesthesia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Syncope	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Somnolence	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Neuropathy peripheral	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Dizziness postural	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Dizziness	5/245 (2%)		3/86 (3.5%)		0/83 (0%)
Restless legs syndrome	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Dysgeusia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Psychiatric disorders
Anxiety	4/245 (1.6%)		0/86 (0%)		1/83 (1.2%)
Insomnia	5/245 (2%)		1/86 (1.2%)		0/83 (0%)
Sleep disorder	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Mental status changes	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Disorientation	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Renal and urinary disorders
Nephrolithiasis	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Dysuria	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Renal pain	0/245 (0%)		1/86 (1.2%)		0/83 (0%)
Reproductive system and breast disorders
Menorrhagia	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	5/245 (2%)		1/86 (1.2%)		1/83 (1.2%)
Sleep apnoea syndrome	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Dyspnoea	11/245 (4.5%)		0/86 (0%)		1/83 (1.2%)
Oropharyngeal pain	3/245 (1.2%)		0/86 (0%)		0/83 (0%)
Pleural effusion	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Epistaxis	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Wheezing	3/245 (1.2%)		0/86 (0%)		1/83 (1.2%)
Productive cough	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Bronchospasm	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Rhinorrhoea	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Throat irritation	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Dysphonia	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	3/245 (1.2%)		0/86 (0%)		0/83 (0%)
Pruritus	6/245 (2.4%)		2/86 (2.3%)		0/83 (0%)
Dry skin	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Rash	2/245 (0.8%)		0/86 (0%)		0/83 (0%)
Skin discolouration	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Pain of skin	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Keloid scar	0/245 (0%)		0/86 (0%)		1/83 (1.2%)
Vascular disorders
Hypotension	4/245 (1.6%)		1/86 (1.2%)		0/83 (0%)
Hypertension	6/245 (2.4%)		0/86 (0%)		1/83 (1.2%)
Haematoma	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Hot flush	1/245 (0.4%)		0/86 (0%)		0/83 (0%)
Intermittent claudication	0/245 (0%)		0/86 (0%)		1/83 (1.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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