Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00995930
• Collaborator: (none)
• Enrollment: 189
• Locations: 9
• Arms: 2
• Duration (Months): 50
• Patients Per Site: 21
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will evaluate the effect of ACZ885 on vascular function in patients with documented atherosclerotic disease and T2DM or IGT.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2; Atherosclerosis; Prediabetic State	Drug: ACZ885; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized , Double Blind, Placebo-controlled, Study of the Safety, Tolerability, and Effects on Arterial Structure and Function of ACZ885 in Patients With Clinically Evident Atherosclerosis and Either T2DM or IGT
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo subcutaneous (SQ) monthly	Drug: Placebo; Matching placebo to ACZ885 was administered subcutaneously once a month for 12 months.
Experimental: ACZ885 150 mg SQ monthly	Drug: ACZ885; ACZ885 150 mg was administered subcutaneously once a month for 12 months.; Other Names: Canakinumab

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events, Serious Adverse Events and Death [12 months]

   Participants were monitored for adverse events, serious adverse events and death throughout the study.

2. Change From Baseline in Aortic Distensibility [baseline, 3 months, 12 months]

   Two axial, ECG-gated, steady state free precession (SSFP) 'cine' images were acquired during breath-hold to determine aortic distensibility. The first image was obtained at the level of the right pulmonary artery through the ascending and proximal descending aorta and the second through the distal aorta below the diaphragm. Imaging of the aorta also enabled evaluation of the plaque burden and additional vascular function measures.

3. Change From Baseline in Plaque Burden (Aortic Vessel Wall Area and Carotid Vessel Wall Area) [baseline, 3 months, 12 months]

   For assessment of atherosclerotic plaque burden of the aorta, vessel wall images of the aorta were acquired with an ECG gated double-inversion recovery (black blood) fast spin echo sequence applied breath-holding. Using an oblique sagittal image of the aorta as a pilot, serial axial images were acquired to cover a section of the descending thoracic aorta. The midpoint of the right pulmonary artery in cross section was used as the anatomical reference for the first slice in baseline and follow-up scans. For assessment of the atherosclerotic plaque burden in the carotids, vessel wall images were acquired with an axial ECG gated PD (proton density) weighted black blood sequence. The carotid bifurcation was used as the anatomical reference for all three imaging time points (baseline, 12 weeks, 48 weeks) with axial slice planes acquired below the bifurcation region. The mean values reported here for the carotid are reported for the proximal common carotid region.

Secondary Outcome Measures

1. Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error [baseline, 3 months, 12 months]

   Utilizing the SphygmoCor Device, ECG leads placed at the carotid and femoral arteries provided the measure of the pulse wave at that particular arterial location. The distance between the two vascular beds divided by the pulse wave time shift provided a measure of the pulse wave velocity.

2. Change From Baseline in Plaque Composition [baseline, 3 months, 12 months]

   During the carotid MRI acquisition, in addition to the PD weighted ECG gated double inversion fast spin echo sequences T1 and T2 weighted sequences were acquired. In combination with the PD weighted images, the multi-contrast images were analyzed to determine regions of interest with contrast patterns consistent with the presence of necrotic lipid core, calcification and fibrous tissue in participants who had complex carotid plaque present in the bifurcation region.

3. Change From Baseline in Aortic Strain [baseline, 3 months, 12 months]

   Arterial strain was computed directly from the cine SSFP images and the change in lumen diameters over the cardiac cycle. The value was independent of pulse pressure and is unitless ratio derived from the maximum to minimum lumen diameters diastole and systole, respectively..

4. Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) [baseline, 3 months, 12 months]

   Blood samples were collected to analyze hsCRP.

5. Change From Baseline in Fasting Plasma Glucose [baseline, 3 months, 12 months]

   Blood samples were collected to analyze fasting plasma glucose.

6. Change From Baseline in Hemoglobin A1c (HbA1c) [baseline, 3 months, 12 months]

   Blood samples were collected to analyze HbA1c.

7. Change From Baseline in 2 Hour Glucose Post Oral Glucose Tolerance Test (OGTT) [baseline, 3 months, 12 months]

   Blood samples were collected to analyze the 2 hour glucose post OGTT.

8. Change From Baseline in Beta Cell Function (HOMA-B) [baseline, 3 months, 12 months]

   Blood samples were collected to analyze beta cell function. Beta cell function was calculated by the Homeostasis Model Assessments (of beta cell function (HOMA-B) as follows: HOMA-B: The product of 20 and basal insulin (µU/mL) levels divided by the value of basal glucose (mmol/L) concentrations minus 3.5 [i.e., HOMA-B = 20*basal insulin/(basal glucose-3.5)].

9. Change From Baseline Insulin Resistance (HOMA-IR) [baseline, 3 months, 12 months]

   Blood samples were collected to analyze insulin resistance. Insulin resistance was calculated by the Homeostasis Model Assessments of insulin resistance (HOMA-IR)) as follows: HOMA-IR: The product of basal glucose (mmol/L) and insulin (µU/mL) levels divided by 22.5 [i.e., HOMA-IR = basal glucose*basal insulin/22.5].

10. Pharmacokinetics: ACZ885 Serum Concentrations [pre-dose, 0.167 day post dose 1, 7 days post dose 1, 14 days post dose 1, every 30 days post each dose from doses 1 through 12, 60 days post dose 12, 90 days post dose 12]

    Blood samples were collected to analyze the ACZ885 serum concentrations.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with known atherosclerotic disease and documented diagnosis of T2DM for ≤ 14 years OR IGT

• HbA1c between 6.0% and 10.0%

• On stable statin therapy or statin intolerant

• Patients who are eligible and able to participate in the study

Exclusion Criteria:

• Contraindications to MRI

• NYHA class IV Heart Failure

• NYHA class I - III heart failure with acute exacerbation in 3 months prior to screening

• Patients with type 1 diabetes

• Acute infections

• HsCRP > 30 mg/dL

• Aortic aneurysm ≥5cm

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	New York	New York	United States	10029
2	Novartis Investigative Site	Cincinnati	Ohio	United States	45219
3	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 1C8
4	Novartis Investigative Site	Mainz		Germany	55116
5	Novartis Investigative Site	Neuss		Germany	41460
6	Novartis Investigative Site	Ulm		Germany	89081
7	Novartis Investigative Site	Jerusalem		Israel	91120
8	Novartis Investigative Site	Oxford	UK	United Kingdom	OX2 6HE
9	Novartis Investigative Site	London		United Kingdom	EC1M 6BQ

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00995930
• Other Study ID Numbers: CACZ885I2206; 2009-014618-80
• First Posted: Oct 16, 2009
• Last Update Posted: Jun 29, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Atherosclerosis,; Type 2 Diabetes Mellitus, T2DM,; Cardiovascular Diseases, ACZ885, impaired glucose tolerance, IGT, Canakinumab
• Additional relevant MeSH terms: Atherosclerosis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Prediabetic State

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 1:1 ratio to each treatment arm.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Period Title: Overall Study
STARTED	94	95
Safety Analysis Set	94	95
Pharmacokinetic (PK) Analysis Set	0	95
Pharmacodynamic (PD) Analysis Set	92	92
Imaging Analysis Set	92	92
COMPLETED	73	67
NOT COMPLETED	21	28

Baseline Characteristics

Arm/Group Title	Placebo	ACZ885	Total
Arm/Group Description	SQ monthly	150 mg SQ monthly	Total of all reporting groups
Overall Participants	94	95	189
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.9 (6.92)	61.7 (7.85)	61.8 (7.38)
Sex: Female, Male (Count of Participants)
Female	14 14.9%	13 13.7%	27 14.3%
Male	80 85.1%	82 86.3%	162 85.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events, Serious Adverse Events and Death
Description	Participants were monitored for adverse events, serious adverse events and death throughout the study.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	94	95
Adverse events (serious and non-serious)	80 85.1%	77 81.1%
Serious adverse events	14 14.9%	25 26.3%
Deaths	0 0%	1 1.1%

2. Primary Outcome

Title	Change From Baseline in Aortic Distensibility
Description	Two axial, ECG-gated, steady state free precession (SSFP) 'cine' images were acquired during breath-hold to determine aortic distensibility. The first image was obtained at the level of the right pulmonary artery through the ascending and proximal descending aorta and the second through the distal aorta below the diaphragm. Imaging of the aorta also enabled evaluation of the plaque burden and additional vascular function measures.
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the imaging analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The imaging analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
3 months, proximal ascending region (n=61,63)	-0.0001 (0.0001)	0.0001 (0.0001)
12 months, proximal ascending region (n=56,55)	-0.0001 (0.0001)	-0.0001 (0.0001)

3. Primary Outcome

Title	Change From Baseline in Plaque Burden (Aortic Vessel Wall Area and Carotid Vessel Wall Area)
Description	For assessment of atherosclerotic plaque burden of the aorta, vessel wall images of the aorta were acquired with an ECG gated double-inversion recovery (black blood) fast spin echo sequence applied breath-holding. Using an oblique sagittal image of the aorta as a pilot, serial axial images were acquired to cover a section of the descending thoracic aorta. The midpoint of the right pulmonary artery in cross section was used as the anatomical reference for the first slice in baseline and follow-up scans. For assessment of the atherosclerotic plaque burden in the carotids, vessel wall images were acquired with an axial ECG gated PD (proton density) weighted black blood sequence. The carotid bifurcation was used as the anatomical reference for all three imaging time points (baseline, 12 weeks, 48 weeks) with axial slice planes acquired below the bifurcation region. The mean values reported here for the carotid are reported for the proximal common carotid region.
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the imaging analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The imaging analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
aortic, proximal ascending, 3 months (n=69,62)	14.80 (6.86)	-0.51 (6.62)
aortic, proximal ascending, 12 months (n=61,53)	30.58 (10.46)	8.71 (10.49)
carotid, mean (right and left), 3 months (n=66,59)	1.41 (1.10)	-0.29 (1.12)
carotid, mean (right and left), 12 mos. (n=55,48)	3.50 (1.51)	0.73 (1.48)

4. Secondary Outcome

Title	Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error
Description	Utilizing the SphygmoCor Device, ECG leads placed at the carotid and femoral arteries provided the measure of the pulse wave at that particular arterial location. The distance between the two vascular beds divided by the pulse wave time shift provided a measure of the pulse wave velocity.
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the imaging analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The imaging analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
pulse wave velocity, 3 months(n=45,38)	-0.39 (0.39)	-0.03 (0.39)
pulse wave velocity, 12 months(n=35,31)	-0.36 (0.35)	-0.26 (0.35)
pulse wave velocity error, 3 months (n=45,38)	-0.01 (0.05)	-0.03 (0.05)
pulse wave velocity error, 12 months (n=35,31)	-0.01 (0.06)	0.06 (0.06)

5. Secondary Outcome

Title	Change From Baseline in Plaque Composition
Description	During the carotid MRI acquisition, in addition to the PD weighted ECG gated double inversion fast spin echo sequences T1 and T2 weighted sequences were acquired. In combination with the PD weighted images, the multi-contrast images were analyzed to determine regions of interest with contrast patterns consistent with the presence of necrotic lipid core, calcification and fibrous tissue in participants who had complex carotid plaque present in the bifurcation region.
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the imaging analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The imaging analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	5	3
calcium composition, left carotid, 3 months	0.002 (0.0045)	0.003 (0.0058)
calcium composition, left carotid, 12 months	0.002 (0.0045)	0.003 (0.0058)
hemorrhage area, left carotid, 3 months	0.006 (0.0114)	-0.000 (0.0200)
hemorrhage area, left carotid, 12 months	0.018 (0.0205)	0.007 (0.0115)
lipid composition, left carotid, 3 months	0.000 (0.0000)	0.003 (0.0115)
lipid composition, left carotid, 12 months	-0.000 (0.0122)	0.007 (0.0058)
calcium composition,right carotid, 3 mos.(n=4,3)	-0.005 (0.0058)	-0.003 (0.0058)
calcium composition,right carotid, 12 mos.(n=4,3)	0.000 (0.0082)	0.000 (0.0000)
hemorrhage area,right carotid, 3 months (n=4,3)	0.003 (0.0096)	-0.000 (0.0100)
hemorrhage area, right carotid, 12 months (n=4,3)	0.008 (0.0330)	0.003 (0.0208)
lipid composition, right carotid, 3 months (n=4,3)	-0.005 (0.0058)	0.003 (0.0058)
lipid composition, right carotid, 12 mos.(n=4,3)	0.008 (0.0171)	0.017 (0.0115)

6. Secondary Outcome

Title	Change From Baseline in Aortic Strain
Description	Arterial strain was computed directly from the cine SSFP images and the change in lumen diameters over the cardiac cycle. The value was independent of pulse pressure and is unitless ratio derived from the maximum to minimum lumen diameters diastole and systole, respectively..
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the imaging analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The imaging analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
proximal ascending, 3 months(n=67,64)	-0.005 (0.005)	0.002 (0.005)
proximal ascending, 12 months(n=59,59)	0.001 (0.005)	-0.002 (0.005)

7. Secondary Outcome

Title	Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)
Description	Blood samples were collected to analyze hsCRP.
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the PD analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The PD analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
3 months (n=82,79)	0.93	0.48
12 months (n=73,68)	1.04	0.51

8. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose
Description	Blood samples were collected to analyze fasting plasma glucose.
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the PD analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The PD analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
3 months (n=79,75)	0.95	1.00
12 months (n=71,62)	0.95	0.99

9. Secondary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c)
Description	Blood samples were collected to analyze HbA1c.
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the PD analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The PD analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
3 months (n=81,77)	1.00	0.99
12 months (n=72,65)	1.00	0.96

10. Secondary Outcome

Title	Change From Baseline in 2 Hour Glucose Post Oral Glucose Tolerance Test (OGTT)
Description	Blood samples were collected to analyze the 2 hour glucose post OGTT.
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the PD analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The PD analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
3 months (n=79,74)	0.92	0.98
12 months (n=71,62)	0.93	0.95

11. Secondary Outcome

Title	Change From Baseline in Beta Cell Function (HOMA-B)
Description	Blood samples were collected to analyze beta cell function. Beta cell function was calculated by the Homeostasis Model Assessments (of beta cell function (HOMA-B) as follows: HOMA-B: The product of 20 and basal insulin (µU/mL) levels divided by the value of basal glucose (mmol/L) concentrations minus 3.5 [i.e., HOMA-B = 20*basal insulin/(basal glucose-3.5)].
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the PD analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The PD analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
HOMA-B, 3 months (n=77,70)	1.11	0.99
HOMA-B, 12 months (n=71,60)	1.03	0.91

12. Secondary Outcome

Title	Change From Baseline Insulin Resistance (HOMA-IR)
Description	Blood samples were collected to analyze insulin resistance. Insulin resistance was calculated by the Homeostasis Model Assessments of insulin resistance (HOMA-IR)) as follows: HOMA-IR: The product of basal glucose (mmol/L) and insulin (µU/mL) levels divided by 22.5 [i.e., HOMA-IR = basal glucose*basal insulin/22.5].
Time Frame	baseline, 3 months, 12 months

Outcome Measure Data

Analysis Population Description

Only participants from the PD analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The PD analysis set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Placebo	ACZ885
Arm/Group Description	SQ monthly	150 mg SQ monthly
Measure Participants	92	92
HOMA-R, 3 months (n=77,70)	1.00	1.09
HOMA-R, 12 months (n=71,60)	0.93	0.97

13. Secondary Outcome

Title	Pharmacokinetics: ACZ885 Serum Concentrations
Description	Blood samples were collected to analyze the ACZ885 serum concentrations.
Time Frame	pre-dose, 0.167 day post dose 1, 7 days post dose 1, 14 days post dose 1, every 30 days post each dose from doses 1 through 12, 60 days post dose 12, 90 days post dose 12

Outcome Measure Data

Analysis Population Description

Only participants from the PK analysis set, who had evaluable data at each time point, were included in the analysis for that time point. The PK analysis set included randomized participants from the ACZ885 arm who received at least one dose of study medication.

Arm/Group Title	ACZ885
Arm/Group Description	150 mg SQ monthly
Measure Participants	95
pre-dose (n=91)	0 (0)
0.167 day post dose 1 (n=94)	480 (648)
7 days post dose 1 (n=95)	10107 (4369)
14 days post dose 1 (n=93)	9138 (3527)
30 days post dose 1 (n=90)	5936 (2281)
30 days post dose 2 (n=86)	8136 (3299)
30 days post dose 3 (n=81)	9278 (3795)
30 days post dose 4 (n=78)	10183 (4552)
30 days post dose 5 (n=78)	10164 (4209)
30 days post dose 6 (n=77)	10254 (3916)
30 days post dose 7 (n=76)	10368 (4840)
30 days post dose 8 (n=71)	9745 (4436)
30 days post dose 9 (n=69)	10407 (3967)
30 days post dose 10 (n=71)	10635 (4697)
30 days post dose 11 (n=70)	10612 (4434)
30 days post dose 12 (n=66)	10887 (4785)
60 days post dose 12 (n=66)	4575 (2362)
90 days post dose 12 (n=88)	3241 (2883)

Adverse Events

Arm/Group Title	ACZ885 150mg		Placebo
Arm/Group Description	ACZ885 150mg		SQ monthly
All Cause Mortality
	ACZ885 150mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ACZ885 150mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/95 (26.3%)		14/94 (14.9%)
Cardiac disorders
Acute coronary syndrome	0/95 (0%)		1/94 (1.1%)
Acute myocardial infarction	2/95 (2.1%)		1/94 (1.1%)
Angina pectoris	2/95 (2.1%)		2/94 (2.1%)
Angina unstable	1/95 (1.1%)		0/94 (0%)
Atrial fibrillation	0/95 (0%)		1/94 (1.1%)
Bradycardia	0/95 (0%)		1/94 (1.1%)
Cardiac failure	1/95 (1.1%)		1/94 (1.1%)
Coronary artery disease	0/95 (0%)		2/94 (2.1%)
Myocardial ischaemia	1/95 (1.1%)		0/94 (0%)
Ear and labyrinth disorders
Sudden hearing loss	1/95 (1.1%)		0/94 (0%)
Gastrointestinal disorders
Inguinal hernia, obstructive	0/95 (0%)		1/94 (1.1%)
General disorders
Non-cardiac chest pain	1/95 (1.1%)		0/94 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/95 (0%)		1/94 (1.1%)
Infections and infestations
Epiglottitis	1/95 (1.1%)		0/94 (0%)
Furuncle	1/95 (1.1%)		0/94 (0%)
Gastroenteritis	0/95 (0%)		1/94 (1.1%)
Localised infection	1/95 (1.1%)		0/94 (0%)
Urinary tract infection	1/95 (1.1%)		0/94 (0%)
Injury, poisoning and procedural complications
Coronary artery restenosis	0/95 (0%)		1/94 (1.1%)
Fall	1/95 (1.1%)		0/94 (0%)
Femur fracture	0/95 (0%)		1/94 (1.1%)
Subdural haematoma	1/95 (1.1%)		0/94 (0%)
Investigations
Hepatic enzyme increased	1/95 (1.1%)		0/94 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/95 (0%)		1/94 (1.1%)
Hypokalaemia	0/95 (0%)		1/94 (1.1%)
Musculoskeletal and connective tissue disorders
Back pain	0/95 (0%)		1/94 (1.1%)
Gouty tophus	1/95 (1.1%)		0/94 (0%)
Lumbar spinal stenosis	0/95 (0%)		1/94 (1.1%)
Musculoskeletal chest pain	1/95 (1.1%)		0/94 (0%)
Osteoarthritis	1/95 (1.1%)		0/94 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/95 (0%)		1/94 (1.1%)
Hepatic cancer	1/95 (1.1%)		0/94 (0%)
Malignant melanoma	1/95 (1.1%)		0/94 (0%)
Myelodysplastic syndrome	1/95 (1.1%)		0/94 (0%)
Nervous system disorders
Carotid artery stenosis	0/95 (0%)		1/94 (1.1%)
Dizziness	1/95 (1.1%)		0/94 (0%)
Hydrocephalus	1/95 (1.1%)		0/94 (0%)
Intraventricular haemorrhage	1/95 (1.1%)		0/94 (0%)
Syncope	1/95 (1.1%)		0/94 (0%)
Transient ischaemic attack	2/95 (2.1%)		0/94 (0%)
Psychiatric disorders
Anxiety	1/95 (1.1%)		0/94 (0%)
Renal and urinary disorders
Nephrolithiasis	1/95 (1.1%)		0/94 (0%)
Renal failure	1/95 (1.1%)		0/94 (0%)
Reproductive system and breast disorders
Epididymitis	1/95 (1.1%)		0/94 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/95 (0%)		1/94 (1.1%)
Pulmonary oedema	0/95 (0%)		1/94 (1.1%)
Skin and subcutaneous tissue disorders
Diabetic foot	1/95 (1.1%)		0/94 (0%)
Vascular disorders
Peripheral artery thrombosis	1/95 (1.1%)		0/94 (0%)
Peripheral vascular disorder	1/95 (1.1%)		0/94 (0%)
Other (Not Including Serious) Adverse Events
	ACZ885 150mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/95 (48.4%)		65/94 (69.1%)
Gastrointestinal disorders
Diarrhoea	5/95 (5.3%)		6/94 (6.4%)
Nausea	4/95 (4.2%)		7/94 (7.4%)
Vomiting	0/95 (0%)		5/94 (5.3%)
General disorders
Asthenia	2/95 (2.1%)		5/94 (5.3%)
Fatigue	2/95 (2.1%)		8/94 (8.5%)
Influenza like illness	4/95 (4.2%)		5/94 (5.3%)
Non-cardiac chest pain	3/95 (3.2%)		8/94 (8.5%)
Infections and infestations
Nasopharyngitis	12/95 (12.6%)		18/94 (19.1%)
Upper respiratory tract infection	9/95 (9.5%)		10/94 (10.6%)
Investigations
Blood creatine phosphokinase increased	5/95 (5.3%)		3/94 (3.2%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	1/95 (1.1%)		5/94 (5.3%)
Musculoskeletal and connective tissue disorders
Back pain	4/95 (4.2%)		5/94 (5.3%)
Musculoskeletal pain	4/95 (4.2%)		7/94 (7.4%)
Nervous system disorders
Dizziness	5/95 (5.3%)		5/94 (5.3%)
Headache	4/95 (4.2%)		5/94 (5.3%)
Renal and urinary disorders
Renal failure	2/95 (2.1%)		6/94 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough	5/95 (5.3%)		2/94 (2.1%)
Skin and subcutaneous tissue disorders
Pruritus	2/95 (2.1%)		6/94 (6.4%)
Vascular disorders
Hypertension	3/95 (3.2%)		5/94 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.