Study of MCI-196 in Chronic Kidney Disease Stage V Subjects on Dialysis With Hyperphosphatemia

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00772382
• Collaborator: (none)
• Enrollment: 116
• Locations: 21
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective of this study is to demonstrate the long-term safety and tolerability of MCI-196 in the subjects with stage V chronic kidney disease on dialysis with hyperphosphatemia.

The secondary objective of this study is to assess the long-term efficacy of flexible doses of MCI-196.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multi-center, Open Label, Flexible Dose, Long Term Safety Study of MCI-196 in Chronic Kidney Disease Stage V Subjects on Dialysis With Hyperphosphatemia
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MCI-196	Drug: MCI-196; 3g to 15g/day (3 times a day), Tablet, 52 weeks of flexible dose; Other Names: Colestilan(INN) Colestimide(JAN) CHOLEBINE® BindRen®

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events (AE) [52 weeks]

Secondary Outcome Measures

1. The Change in Serum Phosphorus From Baseline to Week 52 [52 weeks]

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 have stable phosphate control

• Subjects on stabilized phosphorus diet

• Subjects undergoing regular dialysis treatment

• Females 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 him/her 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/L

• 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 HIV 1 and 2 antibodies

• 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		Los Angeles	California	United States
2		Orange	California	United States
3		Tarzana	California	United States
4		Orlando	Florida	United States
5		Pembroke Pines	Florida	United States
6		Atlanta	Georgia	United States
7		Gurnee	Illinois	United States
8		Evansville	Indiana	United States
9		Baton Rouge	Louisiana	United States
10		New Orleans	Louisiana	United States
11		Northport	New York	United States
12		Durham	North Carolina	United States
13		Oklahoma City	Oklahoma	United States
14		Nashville	Tennessee	United States
15		Houston	Texas	United States
16		Burlington	Vermont	United States
17		Chesapeake	Virginia	United States
18		Kamloops	British Columbia	Canada
19		London	Ontario	Canada
20		Toronto	Ontario	Canada
21		Montreal	Quebec	Canada

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: NCT00772382
• Other Study ID Numbers: MCI-196-A06
• First Posted: Oct 15, 2008
• 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
Arm/Group Description	3, 6, 9, 12, or 15 g/ day as titrated
Period Title: Overall Study
STARTED	116
COMPLETED	61
NOT COMPLETED	55

Baseline Characteristics

Arm/Group Title	MCI-196
Arm/Group Description	3, 6, 9, 12, or 15 g/ day as titrated
Overall Participants	116
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (13.8)
Sex: Female, Male (Count of Participants)
Female	40 34.5%
Male	76 65.5%

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events (AE)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MCI-196
Arm/Group Description	3, 6, 9, 12, or 15 g/ day as titrated
Measure Participants	116
At least 1 treatment-emergent AE	109 94%
At least 1 drug-related treatment-emergent AE	50 43.1%
At least 1 treatment-emergent serious AE	63 54.3%

2. Secondary Outcome

Title	The Change in Serum Phosphorus From Baseline to Week 52
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) with last observation carried forward (LOCF). (ITT population included all enrolled subjects who took at least one dose of study medication and had at least one post-enrollment efficacy value after the start of study medication.)

Arm/Group Title	MCI-196
Arm/Group Description	3, 6, 9, 12, or 15 g/ day as titrated
Measure Participants	116
Mean (95% Confidence Interval) [mg/dL]	-1.18 (2.05)

Adverse Events

Time Frame	52 weeks
Arm/Group Title	MCI-196
Arm/Group Description	3, 6, 9, 12, or 15 g/ day as titrated
All Cause Mortality
	MCI-196
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	MCI-196
	Affected / at Risk (%)	# Events
Total	63/116 (54.3%)
Blood and lymphatic system disorders
Anaemia	3/116 (2.6%)
Pancytopenia	1/116 (0.9%)
Haemorrhagic anaemia	2/116 (1.7%)
Cardiac disorders
Cardiac failure congestive	7/116 (6%)
Angina pectoris	3/116 (2.6%)
Coronary artery disease	9/116 (7.8%)
Cardiac discomfort	1/116 (0.9%)
Acute myocardial infarction	2/116 (1.7%)
Atrial fibrillation	5/116 (4.3%)
Myocardial ischaemia	1/116 (0.9%)
Angina unstable	1/116 (0.9%)
Cardiomyopathy	1/116 (0.9%)
Cardiac arrest	3/116 (2.6%)
Atrial flutter	1/116 (0.9%)
Supraventricular tachycardia	1/116 (0.9%)
Congenital, familial and genetic disorders
Gastrointestinal arteriovenous malformation	1/116 (0.9%)
Gastrointestinal disorders
Ascites	1/116 (0.9%)
Pneumatosis intestinalis	1/116 (0.9%)
Constipation	1/116 (0.9%)
Dysphagia	1/116 (0.9%)
Gastritis	1/116 (0.9%)
Gastrointestinal haemorrhage	1/116 (0.9%)
Nausea	1/116 (0.9%)
Vomiting	2/116 (1.7%)
Diarrhoea	1/116 (0.9%)
Abdominal pain	1/116 (0.9%)
Pancreatitis	1/116 (0.9%)
Mallory-Weiss syndrome	1/116 (0.9%)
Upper gastrointestinal haemorrhage	1/116 (0.9%)
Oesophageal stenosis	1/116 (0.9%)
General disorders
Pyrexia	3/116 (2.6%)
Catheter related complication	3/116 (2.6%)
Non-cardiac chest pain	3/116 (2.6%)
Chest pain	1/116 (0.9%)
Hepatobiliary disorders
Cholecystitis	1/116 (0.9%)
Infections and infestations
Bacteraemia	2/116 (1.7%)
Pharyngeal abscess	1/116 (0.9%)
Diabetic foot infection	1/116 (0.9%)
Pneumonia	7/116 (6%)
Sepsis	6/116 (5.2%)
Gastroenteritis	2/116 (1.7%)
Urinary tract infection	5/116 (4.3%)
Wound infection staphylococcal	1/116 (0.9%)
Wound infection	1/116 (0.9%)
Escherichia urinary tract infection	1/116 (0.9%)
Gangrene	3/116 (2.6%)
Peritonitis bacterial	1/116 (0.9%)
Bronchitis	1/116 (0.9%)
Cellulitis	3/116 (2.6%)
Bacterial sepsis	1/116 (0.9%)
Arteriovenous graft site infection	1/116 (0.9%)
Helicobacter gastritis	1/116 (0.9%)
Injury, poisoning and procedural complications
Fall	1/116 (0.9%)
Femur fracture	1/116 (0.9%)
Tibia fracture	1/116 (0.9%)
Arteriovenous graft thrombosis	3/116 (2.6%)
Arteriovenous fistula occlusion	1/116 (0.9%)
Arteriovenous fistula aneurysm	1/116 (0.9%)
Hip fracture	1/116 (0.9%)
In-stent coronary artery restenosis	1/116 (0.9%)
Vena cava injury	1/116 (0.9%)
Arteriovenous fistula site complication	1/116 (0.9%)
Procedural pain	1/116 (0.9%)
Investigations
Ammonia increased	1/116 (0.9%)
International normalised ratio increased	1/116 (0.9%)
Metabolism and nutrition disorders
Fluid overload	5/116 (4.3%)
Diabetic ketoacidosis	1/116 (0.9%)
Hyperglycaemia	1/116 (0.9%)
Hyperkalaemia	6/116 (5.2%)
Calciphylaxis	2/116 (1.7%)
Electrolyte imbalance	1/116 (0.9%)
Hypoglycaemia	2/116 (1.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/116 (0.9%)
Musculoskeletal pain	1/116 (0.9%)
Osteoarthritis	1/116 (0.9%)
Back pain	1/116 (0.9%)
Muscular weakness	1/116 (0.9%)
Pain in extremity	1/116 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic	1/116 (0.9%)
Prostate cancer	1/116 (0.9%)
Nervous system disorders
Transient ischaemic attack	1/116 (0.9%)
Lacunar infarction	1/116 (0.9%)
Metabolic encephalopathy	1/116 (0.9%)
Partial seizures	1/116 (0.9%)
Cerebrovascular accident	3/116 (2.6%)
Carotid artery stenosis	2/116 (1.7%)
Psychiatric disorders
Mental status changes	1/116 (0.9%)
Drug abuse	1/116 (0.9%)
Renal and urinary disorders
Lupus nephritis	1/116 (0.9%)
Azotaemia	1/116 (0.9%)
Renal failure acute	1/116 (0.9%)
Hydronephrosis	1/116 (0.9%)
Renal cyst ruptured	1/116 (0.9%)
Nephrolithiasis	1/116 (0.9%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	3/116 (2.6%)
Dyspnoea	5/116 (4.3%)
Pulmonary fibrosis	1/116 (0.9%)
Acute pulmonary oedema	1/116 (0.9%)
Respiratory failure	3/116 (2.6%)
Hypoxia	2/116 (1.7%)
Pleuritic pain	1/116 (0.9%)
Chronic obstructive pulmonary disease	2/116 (1.7%)
Pneumonitis	1/116 (0.9%)
Epistaxis	1/116 (0.9%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/116 (0.9%)
Vascular disorders
Hypertensive crisis	3/116 (2.6%)
Arteriosclerosis obliterans	1/116 (0.9%)
Haemorrhage	1/116 (0.9%)
Jugular vein thrombosis	1/116 (0.9%)
Malignant hypertension	2/116 (1.7%)
Superior vena caval occlusion	1/116 (0.9%)
Vena cava thrombosis	1/116 (0.9%)
Accelerated hypertension	1/116 (0.9%)
Peripheral arterial occlusive disease	1/116 (0.9%)
Venous stenosis	1/116 (0.9%)
Peripheral vascular disorder	1/116 (0.9%)
Deep vein thrombosis	2/116 (1.7%)
Hypotension	2/116 (1.7%)
Steal syndrome	1/116 (0.9%)
Other (Not Including Serious) Adverse Events
	MCI-196
	Affected / at Risk (%)	# Events
Total	106/116 (91.4%)
Blood and lymphatic system disorders
Anaemia	8/116 (6.9%)
Thrombocytopenia	2/116 (1.7%)
Leukocytosis	1/116 (0.9%)
Leukopenia	2/116 (1.7%)
Cardiac disorders
Atrial fibrillation	4/116 (3.4%)
Bradycardia	2/116 (1.7%)
Angina pectoris	5/116 (4.3%)
Diastolic dysfunction	1/116 (0.9%)
Coronary artery occlusion	1/116 (0.9%)
Tachycardia	2/116 (1.7%)
Atrioventricular block first degree	1/116 (0.9%)
Cardiac failure congestive	1/116 (0.9%)
Conduction disorder	1/116 (0.9%)
Bundle branch block left	1/116 (0.9%)
Cardiac tamponade	1/116 (0.9%)
Cardiomyopathy	1/116 (0.9%)
Atrial flutter	1/116 (0.9%)
Cardiomegaly	2/116 (1.7%)
Supraventricular tachycardia	1/116 (0.9%)
Mitral valve incompetence	1/116 (0.9%)
Tachyarrhythmia	1/116 (0.9%)
Coronary artery disease	1/116 (0.9%)
Congenital, familial and genetic disorders
Atrial septal defect	1/116 (0.9%)
Ear and labyrinth disorders
Inner ear inflammation	1/116 (0.9%)
Sudden hearing loss	1/116 (0.9%)
Endocrine disorders
Hypothyroidism	2/116 (1.7%)
Hyperparathyroidism secondary	2/116 (1.7%)
Eye disorders
Scleral haemorrhage	1/116 (0.9%)
Eye swelling	1/116 (0.9%)
Ocular hyperaemia	1/116 (0.9%)
Conjunctivitis allergic	1/116 (0.9%)
Conjunctivitis	1/116 (0.9%)
Cataract	1/116 (0.9%)
Eye irritation	1/116 (0.9%)
Gastrointestinal disorders
Abdominal discomfort	7/116 (6%)
Abdominal distension	1/116 (0.9%)
Ascites	5/116 (4.3%)
Diarrhoea	23/116 (19.8%)
Flatulence	2/116 (1.7%)
Impaired gastric emptying	1/116 (0.9%)
Vomiting	24/116 (20.7%)
Nausea	26/116 (22.4%)
Abdominal pain	5/116 (4.3%)
Oesophagitis	1/116 (0.9%)
Reflux gastritis	1/116 (0.9%)
Abdominal pain upper	1/116 (0.9%)
Abdominal pain lower	2/116 (1.7%)
Hypoaesthesia oral	1/116 (0.9%)
Constipation	11/116 (9.5%)
Dyspepsia	10/116 (8.6%)
Stomatitis	1/116 (0.9%)
Haematochezia	1/116 (0.9%)
Dysphagia	2/116 (1.7%)
Faecaloma	1/116 (0.9%)
Ileus	2/116 (1.7%)
Colitis	1/116 (0.9%)
Toothache	2/116 (1.7%)
Abdominal adhesions	1/116 (0.9%)
Diverticulum intestinal	1/116 (0.9%)
Haemorrhoids	1/116 (0.9%)
Polyp colorectal	1/116 (0.9%)
Glossodynia	1/116 (0.9%)
Gastrointestinal haemorrhage	1/116 (0.9%)
Rectal haemorrhage	2/116 (1.7%)
Umbilical hernia, obstructive	1/116 (0.9%)
Colonic polyp	1/116 (0.9%)
Hiatus hernia	1/116 (0.9%)
Gastrooesophageal reflux disease	2/116 (1.7%)
Melaena	1/116 (0.9%)
Oesophageal stenosis	1/116 (0.9%)
General disorders
Pyrexia	9/116 (7.8%)
Chest discomfort	3/116 (2.6%)
Asthenia	2/116 (1.7%)
Malaise	4/116 (3.4%)
Oedema peripheral	8/116 (6.9%)
Chest pain	4/116 (3.4%)
Feeling hot	1/116 (0.9%)
Non-cardiac chest pain	2/116 (1.7%)
Feeling cold	1/116 (0.9%)
Face oedema	3/116 (2.6%)
Fatigue	2/116 (1.7%)
Local swelling	1/116 (0.9%)
Localised oedema	1/116 (0.9%)
Chills	4/116 (3.4%)
Pain	1/116 (0.9%)
Influenza like illness	2/116 (1.7%)
Gait disturbance	2/116 (1.7%)
Catheter related complication	1/116 (0.9%)
Vessel puncture site haemorrhage	1/116 (0.9%)
Inflammation	1/116 (0.9%)
Catheter site pain	1/116 (0.9%)
Hepatobiliary disorders
Gallbladder polyp	1/116 (0.9%)
Immune system disorders
Seasonal allergy	2/116 (1.7%)
Infections and infestations
Herpes zoster	1/116 (0.9%)
Lower respiratory tract infection	1/116 (0.9%)
Clostridial infection	3/116 (2.6%)
Pulmonary tuberculosis	1/116 (0.9%)
Urinary tract infection	8/116 (6.9%)
Cellulitis	2/116 (1.7%)
Gangrene	2/116 (1.7%)
Localised infection	1/116 (0.9%)
Nail infection	1/116 (0.9%)
Osteomyelitis	1/116 (0.9%)
Gastroenteritis	3/116 (2.6%)
Bronchitis	6/116 (5.2%)
Nasopharyngitis	11/116 (9.5%)
Sinusitis	1/116 (0.9%)
Enterococcal infection	2/116 (1.7%)
Postoperative wound infection	1/116 (0.9%)
Upper respiratory tract infection	9/116 (7.8%)
Bacterial disease carrier	1/116 (0.9%)
Subcutaneous abscess	1/116 (0.9%)
Arteriovenous fistula site infection	3/116 (2.6%)
Tooth abscess	1/116 (0.9%)
Clostridium difficile colitis	1/116 (0.9%)
Pneumonia	2/116 (1.7%)
Furuncle	1/116 (0.9%)
Peritonitis bacterial	1/116 (0.9%)
Ear infection	1/116 (0.9%)
Hepatitis C	1/116 (0.9%)
Onychomycosis	1/116 (0.9%)
Catheter related infection	1/116 (0.9%)
Catheter site infection	1/116 (0.9%)
Pleural infection bacterial	1/116 (0.9%)
Staphylococcal infection	2/116 (1.7%)
Graft infection	1/116 (0.9%)
Wound infection staphylococcal	1/116 (0.9%)
Oral candidiasis	1/116 (0.9%)
Oesophageal candidiasis	1/116 (0.9%)
Injury, poisoning and procedural complications
Contusion	2/116 (1.7%)
Fall	3/116 (2.6%)
Haemodialysis-induced symptom	13/116 (11.2%)
Procedural hypertension	1/116 (0.9%)
Arteriovenous fistula site complication	11/116 (9.5%)
Mouth injury	1/116 (0.9%)
Procedural dizziness	1/116 (0.9%)
Skin laceration	2/116 (1.7%)
Arteriovenous fistula occlusion	1/116 (0.9%)
Excoriation	3/116 (2.6%)
Joint sprain	1/116 (0.9%)
Wound	1/116 (0.9%)
Arteriovenous graft site haemorrhage	1/116 (0.9%)
Procedural pain	3/116 (2.6%)
Vascular graft complication	1/116 (0.9%)
Venous injury	1/116 (0.9%)
Foot fracture	1/116 (0.9%)
Arteriovenous fistula aneurysm	2/116 (1.7%)
Arteriovenous fistula site haemorrhage	4/116 (3.4%)
Ulna fracture	1/116 (0.9%)
Limb injury	1/116 (0.9%)
Arteriovenous graft thrombosis	3/116 (2.6%)
Arteriovenous fistula thrombosis	2/116 (1.7%)
Procedural hypotension	2/116 (1.7%)
Post procedural complication	1/116 (0.9%)
Investigations
Breath sounds abnormal	3/116 (2.6%)
Blood cholesterol increased	1/116 (0.9%)
Blood parathyroid hormone increased	1/116 (0.9%)
Methicillin-resistant staphylococcal aureus test positive	1/116 (0.9%)
Electrocardiogram QT prolonged	1/116 (0.9%)
Blood glucose increased	1/116 (0.9%)
Hepatic enzyme increased	1/116 (0.9%)
Blood phosphorus increased	1/116 (0.9%)
Venous pressure increased	1/116 (0.9%)
Ammonia increased	1/116 (0.9%)
Gram stain positive	1/116 (0.9%)
Weight decreased	2/116 (1.7%)
Vitamin D decreased	1/116 (0.9%)
Liver function test abnormal	1/116 (0.9%)
Cardiac murmur	2/116 (1.7%)
Blood creatine phosphokinase increased	2/116 (1.7%)
Chest X-ray abnormal	1/116 (0.9%)
Cardiovascular function test abnormal	1/116 (0.9%)
Activated partial thromboplastin time abnormal	1/116 (0.9%)
International normalised ratio abnormal	1/116 (0.9%)
Prothrombin time abnormal	1/116 (0.9%)
Electrocardiogram T wave abnormal	1/116 (0.9%)
Gamma-glutamyltransferase increased	1/116 (0.9%)
Prostatic specific antigen increased	1/116 (0.9%)
Blood glucose decreased	2/116 (1.7%)
Blood culture positive	1/116 (0.9%)
Metabolism and nutrition disorders
Decreased appetite	14/116 (12.1%)
Hypoglycaemia	5/116 (4.3%)
Hyperkalaemia	7/116 (6%)
Hypocalcaemia	7/116 (6%)
Hypokalaemia	4/116 (3.4%)
Hyperhomocysteinaemia	1/116 (0.9%)
Hypomagnesaemia	1/116 (0.9%)
Metabolic acidosis	1/116 (0.9%)
Diabetes mellitus	3/116 (2.6%)
Hypercalcaemia	2/116 (1.7%)
Iron deficiency	1/116 (0.9%)
Folate deficiency	2/116 (1.7%)
Vitamin D deficiency	1/116 (0.9%)
Hypernatraemia	1/116 (0.9%)
Hypoalbuminaemia	1/116 (0.9%)
Hypophosphataemia	1/116 (0.9%)
Hypervolaemia	2/116 (1.7%)
Increased appetite	1/116 (0.9%)
Musculoskeletal and connective tissue disorders
Muscle tightness	1/116 (0.9%)
Osteoporosis	1/116 (0.9%)
Arthralgia	7/116 (6%)
Neck pain	2/116 (1.7%)
Pain in extremity	8/116 (6.9%)
Joint swelling	3/116 (2.6%)
Musculoskeletal pain	4/116 (3.4%)
Muscle spasms	6/116 (5.2%)
Myalgia	1/116 (0.9%)
Costochondritis	1/116 (0.9%)
Back pain	3/116 (2.6%)
Osteopenia	1/116 (0.9%)
Flank pain	1/116 (0.9%)
Arthritis	1/116 (0.9%)
Bursitis	1/116 (0.9%)
Trigger finger	1/116 (0.9%)
Pain in jaw	1/116 (0.9%)
Groin pain	1/116 (0.9%)
Muscular weakness	1/116 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm	1/116 (0.9%)
Melanocytic naevus	1/116 (0.9%)
Nervous system disorders
Post herpetic neuralgia	1/116 (0.9%)
Cerebrovascular accident	1/116 (0.9%)
Hemiparesis	1/116 (0.9%)
Hypoaesthesia	3/116 (2.6%)
Dizziness	9/116 (7.8%)
Headache	11/116 (9.5%)
Paraesthesia	1/116 (0.9%)
Facial palsy	2/116 (1.7%)
Syncope	1/116 (0.9%)
Dementia	2/116 (1.7%)
Somnolence	1/116 (0.9%)
Altered state of consciousness	1/116 (0.9%)
Presyncope	1/116 (0.9%)
Tremor	1/116 (0.9%)
Aphasia	1/116 (0.9%)
Restless legs syndrome	1/116 (0.9%)
Carotid artery occlusion	1/116 (0.9%)
Carotid artery stenosis	1/116 (0.9%)
Psychiatric disorders
Delirium	1/116 (0.9%)
Confusional state	3/116 (2.6%)
Insomnia	9/116 (7.8%)
Stress	1/116 (0.9%)
Anxiety	4/116 (3.4%)
Drug abuse	1/116 (0.9%)
Depression	2/116 (1.7%)
Renal and urinary disorders
Urinary tract disorder	1/116 (0.9%)
Azotaemia	1/116 (0.9%)
Haematuria	1/116 (0.9%)
Polyuria	1/116 (0.9%)
Renal failure chronic	1/116 (0.9%)
Reproductive system and breast disorders
Erectile dysfunction	2/116 (1.7%)
Respiratory, thoracic and mediastinal disorders
Cough	11/116 (9.5%)
Oropharyngeal pain	1/116 (0.9%)
Dyspnoea	13/116 (11.2%)
Orthopnoea	1/116 (0.9%)
Pleural effusion	4/116 (3.4%)
Sleep apnoea syndrome	1/116 (0.9%)
Pulmonary oedema	2/116 (1.7%)
Wheezing	2/116 (1.7%)
Nasal congestion	2/116 (1.7%)
Pulmonary fibrosis	1/116 (0.9%)
Rhonchi	2/116 (1.7%)
Dyspnoea exertional	3/116 (2.6%)
Chylothorax	1/116 (0.9%)
Productive cough	2/116 (1.7%)
Hypoxia	3/116 (2.6%)
Pneumothorax	1/116 (0.9%)
Atelectasis	3/116 (2.6%)
Pleural rub	1/116 (0.9%)
Rales	2/116 (1.7%)
Pulmonary congestion	1/116 (0.9%)
Pulmonary hypertension	1/116 (0.9%)
Tachypnoea	1/116 (0.9%)
Acute respiratory distress syndrome	1/116 (0.9%)
Epistaxis	1/116 (0.9%)
Hypercapnia	1/116 (0.9%)
Lung infiltration	1/116 (0.9%)
Respiratory failure	1/116 (0.9%)
Skin and subcutaneous tissue disorders
Dermatitis	1/116 (0.9%)
Eczema	1/116 (0.9%)
Skin ulcer	5/116 (4.3%)
Rash generalised	1/116 (0.9%)
Pruritus	5/116 (4.3%)
Blister	1/116 (0.9%)
Ecchymosis	1/116 (0.9%)
Hyperkeratosis	1/116 (0.9%)
Periorbital oedema	2/116 (1.7%)
Post inflammatory pigmentation change	1/116 (0.9%)
Pruritus generalised	2/116 (1.7%)
Rash	1/116 (0.9%)
Rash pruritic	1/116 (0.9%)
Erythema	3/116 (2.6%)
Urticaria	1/116 (0.9%)
Acne	1/116 (0.9%)
Skin lesion	1/116 (0.9%)
Vascular disorders
Hypotension	10/116 (8.6%)
Hypertension	9/116 (7.8%)
Orthostatic hypotension	2/116 (1.7%)
Arteriosclerosis obliterans	1/116 (0.9%)
Air embolism	1/116 (0.9%)
Haematoma	1/116 (0.9%)
Jugular vein distension	1/116 (0.9%)
Vasodilatation	1/116 (0.9%)
Venous occlusion	1/116 (0.9%)
Peripheral arterial occlusive disease	1/116 (0.9%)
Arterial thrombosis limb	1/116 (0.9%)
Aortic dilatation	1/116 (0.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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