Targeted Dose Finding of Canakinumab (ACZ885) for Management of Acute Flare in Refractory or Contraindicated Gout Patients

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00798369
• Collaborator: (none)
• Enrollment: 200
• Locations: 75
• Arms: 6
• Duration (Months): 9
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This 8-week study is designed to determine the target dose of canakinumab (ACZ885) for the management of acute flare in gout patients who are contraindicated to Non-Steroidal anti-inflammatory drugs and/or colchicine. The efficacy of ACZ885 will be compared to the corticosteroid triamcinolone acetonide.

Condition or Disease	Intervention/Treatment	Phase
Acute Gout	Drug: Canakinumab; Drug: Canakinumab; Drug: Canakinumab; Drug: Canakinumab; Drug: Canakinumab; Drug: Triamcinolone acetonide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: An Adaptive Dose-ranging, Multi-center, Single-blind, Double-dummy, Active-controlled Trial to Determine the Target Dose of Canakinumab (ACZ885) in the Treatment of Acute Flares in Gout Patients Who Are Refractory or Contraindicated to NSAIDs and/or Colchicine
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canakinumab 10 mg Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab; Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.
Experimental: Canakinumab 25 mg Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab; Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1.
Experimental: Canakinumab 50 mg Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab; Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1.
Experimental: Canakinumab 90 mg Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab; Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1.
Experimental: Canakinumab 150 mg Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Drug: Canakinumab; Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1.
Active Comparator: Triamcinolone acetonide 40 mg Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once and placebo matching canakinumab s.c. once, on Day 1.	Drug: Triamcinolone acetonide; Randomized patients received triamcinolone acetonide 40 mg i.m. once and placebo matching canakinumab s.c. once, on Day 1.

Outcome Measures

Primary Outcome Measures

1. The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) [at 24,48 and 72 hours post-baseline]

   Mean target dose at 24, 48 and 72 hours. Four models: Emax, Logistic, Linear in log-dose, Linear were selected to describe the potential dose-response curve and hence estimate the target dose of canakinumab using baseline Visual Analog Scale (VAS) and Body Mass Index (BMI) as covariates. Target dose was defined as the dose for which the efficacy is equivalent to the efficacy of triamcinolone acetonide 40 mg and was identified by assessing the dose response relationship with regards to the pain intensity in the target joint measured on a 0- 100 mm VAS (0= no pain and 100= unbearable pain).

Secondary Outcome Measures

1. The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide [Baseline,at 72 hrs post-dose and 7 days post-dose]

   The change in pain intensity from baseline to 72 hours and 7 days post dose as measured on a 0-100 mm Visual Analog Scale(VAS): 0= no pain and 100= severe pain. Analysis of Covariance (ANCOVA) with treatment group, VAS at baseline and Body mass Index (BMI) at baseline as covariates. Change from baseline = (post-baseline measurement - baseline).

2. Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment [at 72 hours post-baseline]

   Participants scored their global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Slight and Poor.

3. The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint [Baseline, within 7 days after randomization]

   The median time in days to at least 50% reduction in Pain intensity from baseline as measured by Visual Analog Scale (VAS) for each treatment group. Participants scored their pain intensity in the target joint on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100).

4. High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group [at 72 hours and 7 days, 4 and 8 weeks post-dose]

   High sensitivity C-reactive protein (hsCRP) was determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates.

5. Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group [at 72 hours and 7 days, 4 and 8 weeks post-dose]

   Serum amyloid A (SAA) were determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates.

6. Amount of Rescue Medication Taken for Each Treatment Group [7 days after study drug administration]

   Participants who had difficulty in tolerating their pain after the 6-hour post-dose pain assessments and during the first 7 study days were allowed to take a maximum of 30 mg prednisolone (or equivalent dose of prednisone [30 mg]) orally once a day for a maximum of 5 days. In addition, participants could use 500 mg acetaminophen (paracetamol) and/or 30 mg codeine as needed during the first 7 study days. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/dose or 180 mg/day of codeine was allowed during the first 7 days of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of at least 1 gout flare prior to the Screening Visit

• Meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout.

• Presence of acute gout flare for no longer than 5 days.

• Baseline pain intensity > or = to 50 mm on the 0-100 mm VAS.

• Contraindicated for, intolerant or unresponsive to NSAIDs, colchicine or both.

Exclusion Criteria:

• Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis.

• Presence of severe renal function impairment

• Contraindication to intramuscular injection

• Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment

• Evidence of active pulmonary disease

• Live vaccinations within 3 months prior to the start of the study

• Use of forbidden therapy

Other protocol-defined inclusion/exclusion criteria applied

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group, LLC	Anniston	Alabama	United States	36207-5710
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
3	Associated Pharmaceutical Research	Buena Park	California	United States	90620
4	Northern California Institute for Bone Health	Oakland	California	United States	94609
5	San Diego Arthritis & Osteoporosis Medical Clinic	San Diego	California	United States	92108
6	Center for Clinical Trials of San Gabriel	West Covina	California	United States	91790
7	Tampa Medical Group, P.A.	Tampa	Florida	United States	33614
8	Florida Medical Clinic, PA	Zephyrhills	Florida	United States	33542
9	Harbin Clinic	Rome	Georgia	United States	30165
10	Intermountain Orthopedics	Boise	Idaho	United States	83702
11	Northwest Clinical Trials	Boise	Idaho	United States	83704
12	The Arthritis Center	Springfield	Illinois	United States	62704
13	Cotton O'Neil Clinic	Topeka	Kansas	United States	66606
14	Arthritis and Diabetes Clinic	Monroe	Louisiana	United States	71203
15	Arthritis Consultants, Inc.	St. Louis	Missouri	United States	63141
16	Billings Clinic Research Center	Billings	Montana	United States	59101
17	Montana Medical Research	Missoula	Montana	United States	59804
18	Heartland Clinical Research, Inc.	Omaha	Nebraska	United States	68134
19	New Mexico Clinical Research & Osteoporosis Center, Inc.	Albuquerque	New Mexico	United States	87106
20	Regional Clinical Research Rheumatology Assoc.	Binghamton	New York	United States	13905
21	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
22	Community Research Partners, Inc.	Varnville	South Carolina	United States	29944
23	Comprehensive Rheumatology	Hendersonville	Tennessee	United States	37075
24	MultiSpecialty Clinical Research	Johnson City	Tennessee	United States	37601
25	Integrity Clinical Research, LLC	Milan	Tennessee	United States	38358
26	Southwest Rheumatology	Mesquite	Texas	United States	75150
27	Health Research of Hampton Roads	Newport News	Virginia	United States	23606
28	Novartis Investigative site	Rosario		Argentina
29	Novartis Investigative site	Gozée		Belgium
30	Novartis Investigative site	Moncton		Canada
31	Novartis Investigative site	Mount Pearl		Canada
32	Novartis Investigative site	St. John's		Canada
33	Novartis Investigative site	Paris cedex 10		France
34	Novartis Investigative Site	Bad Nauheim		Germany
35	Novartis Investigative Site	Bautzen		Germany
36	Novartis Investigative Site	Berlin		Germany
37	Novartis Investigative Site	Chemnitz		Germany
38	Novartis Investigative Site	Dachau		Germany
39	Novartis Investigative Site	Dresden		Germany
40	Novartis Investigative Site	Frankfurt		Germany
41	Novartis Investigative Site	Georgensgmuend		Germany
42	Novartis Investigative Site	Hamburg		Germany
43	Novartis Investigative Site	Leipzig		Germany
44	Novartis Investigative Site	Loehne		Germany
45	Novartis Investigative Site	Magdeburg		Germany
46	Novartis Investigative Site	Messkirch		Germany
47	Novartis Investigative Site	Munich		Germany
48	Novartis Investigative Site	Schwabach		Germany
49	Novartis Investigative Site	Zerbst		Germany
50	Novartis Investigative site	Poznan		Poland
51	Novartis Investigative site	Szczecin		Poland
52	Novartis Investigative site	Wroclaw		Poland
53	Novartis Investigative site	Chelyabinsk		Russian Federation
54	Novartis Investigative Site	Moscow		Russian Federation
55	Novartis Investigative Site	St. Petersburg		Russian Federation
56	Novartis Investigative site	Tyumen		Russian Federation
57	Novartis Investigative Site	Yaroslavl		Russian Federation
58	Novartis Investigative site	Yekaterinburg		Russian Federation
59	Novartis Investigative site	Baden		Switzerland
60	Novartis Investigative site	Basel		Switzerland
61	Novartis Investigative site	Bern		Switzerland
62	Novartis Investigative site	Lausanne		Switzerland
63	Novartis Investigative Site	Adana		Turkey
64	Novartis Investigative Site	Ankara		Turkey
65	Novartis Investigative Site	Antalya		Turkey
66	Novartis Investigative Site	Aydin		Turkey
67	Novartis Investigative Site	Gaziantep		Turkey
68	Novartis Investigative Site	Istanbul		Turkey
69	Novartis Investigative Site	Izmir		Turkey
70	Novartis Investigative Site	Manisa		Turkey
71	Novartis Investigative site	Sihhiye/Ankara		Turkey
72	Novartis Investigative Site	Antrim		United Kingdom
73	Novartis Investigative Site	Coventry		United Kingdom
74	Novartis Investigative Site	Lancashire		United Kingdom
75	Novartis Investigative Site	Wellingborough		United Kingdom

Sponsors and Collaborators

• Novartis

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00798369
• Other Study ID Numbers: CACZ885H2255; EudraCT 2008-004666-61
• First Posted: Nov 26, 2008
• Last Update Posted: Apr 10, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by , ,: Acute flares; Gout; Anti-interleukin-1β monoclonal antibody; Colchicine; Triamcinolone acetonide
• Additional relevant MeSH terms: Gout; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Antibodies, Monoclonal; Triamcinolone diacetate

Study Results

Participant Flow

Arm/Group Title	Canakinumab 10 mg	Canakinumab 25 mg	Canakinumab 50 mg	Canakinumab 90 mg	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.
Period Title: Overall Study
STARTED	28	29	29	29	28	57
COMPLETED	27	28	27	28	27	54
NOT COMPLETED	1	1	2	1	1	3

Baseline Characteristics

Arm/Group Title	Canakinumab 10 mg	Canakinumab 25 mg	Canakinumab 50 mg	Canakinumab 90 mg	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg	Total
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.	Total of all reporting groups
Overall Participants	28	29	29	29	28	57	200
Age, Customized (participants) [Number]
≥18 years - 40 years	6 21.4%	4 13.8%	3 10.3%	5 17.2%	8 28.6%	7 12.3%	33 16.5%
≥ 41 - 64 years	21 75%	21 72.4%	19 65.5%	20 69%	15 53.6%	39 68.4%	135 67.5%
≥ 65 - 74 years	0 0%	3 10.3%	6 20.7%	2 6.9%	3 10.7%	10 17.5%	24 12%
≥ 75 years	1 3.6%	1 3.4%	1 3.4%	2 6.9%	2 7.1%	1 1.8%	8 4%
Sex: Female, Male (Count of Participants)
Female	2 7.1%	3 10.3%	2 6.9%	5 17.2%	0 0%	2 3.5%	14 7%
Male	26 92.9%	26 89.7%	27 93.1%	24 82.8%	28 100%	55 96.5%	186 93%

Outcome Measures

1. Secondary Outcome

Title	The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide
Description	The change in pain intensity from baseline to 72 hours and 7 days post dose as measured on a 0-100 mm Visual Analog Scale(VAS): 0= no pain and 100= severe pain. Analysis of Covariance (ANCOVA) with treatment group, VAS at baseline and Body mass Index (BMI) at baseline as covariates. Change from baseline = (post-baseline measurement - baseline).
Time Frame	Baseline,at 72 hrs post-dose and 7 days post-dose

Outcome Measure Data

Analysis Population Description

Full Analysis Set consisting of all participants with data for baseline and the given time point for each arm/group. Assessments up to Day 8, with 1 missing pain intensity value had it imputed. LOCF method was applied to impute post-dose measurements. Missing baseline values were replaced by the median baseline assessment

Arm/Group Title	Canakinumab 10 mg	Canakinumab 25 mg	Canakinumab 50 mg	Canakinumab 90 mg	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.
Measure Participants	28	29	28	29	27	56
72 hrs post-dose (n= 28, 28, 26, 28, 27, 53)	-48.6 (4.36)	-46.6 (4.39)	-48.6 (4.56)	-52.7 (4.35)	-62.5 (4.58)	-43.3 (3.16)
7 days post-dose (n= 26, 28, 27, 27, 26, 51)	-57.6 (4.06)	-53.9 (3.93)	-63.4 (4.00)	-61.2 (3.96)	-66.4 (4.19)	-56.0 (2.88)

2. Secondary Outcome

Title	Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment
Description	Participants scored their global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Slight and Poor.
Time Frame	at 72 hours post-baseline

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Canakinumab 10 mg	Canakinumab 25 mg	Canakinumab 50 mg	Canakinumab 90 mg	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.
Measure Participants	28	29	28	29	27	56
Number [Percentage of Participants]	64 228.6%	62 213.8%	71 244.8%	66 227.6%	89 317.9%	54 94.7%

3. Secondary Outcome

Title	The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint
Description	The median time in days to at least 50% reduction in Pain intensity from baseline as measured by Visual Analog Scale (VAS) for each treatment group. Participants scored their pain intensity in the target joint on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100).
Time Frame	Baseline, within 7 days after randomization

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Canakinumab 10 mg	Canakinumab 25 mg	Canakinumab 50 mg	Canakinumab 90 mg	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.
Measure Participants	28	29	28	29	27	56
Median (95% Confidence Interval) [Days]	2.9	2.9	1.0	1.0	1.0	2.0

4. Secondary Outcome

Title	High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group
Description	High sensitivity C-reactive protein (hsCRP) was determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates.
Time Frame	at 72 hours and 7 days, 4 and 8 weeks post-dose

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Canakinumab 10 mg	Canakinumab 25 mg	Canakinumab 50 mg	Canakinumab 90 mg	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.
Measure Participants	28	29	28	29	27	56
72 hrs post-dose (n= 27, 28, 26, 28, 25, 53)	16.7 (3.41)	7.9 (3.34)	11.7 (3.49)	13.4 (3.34)	9.2 (3.53)	13.4 (2.43)
7 days post-dose (n= 28, 29, 28, 28, 27, 55)	8.0 (3.30)	2.5 (3.23)	4.3 (3.31)	6.3 (3.29)	3.7 (3.36)	13.7 (2.35)
4 week post-dose (n= 27, 28, 27, 28, 27, 55)	3.0 (3.13)	2.9 (3.08)	2.9 (3.14)	4.8 (3.08)	4.8 (3.13)	9.2 (2.20)
8 weeks post-dose (n= 26, 28, 27, 28, 27, 54)	3.8 (1.79)	2.0 (1.72)	2.6 (1.75)	5.2 (1.72)	2.9 (1.75)	8.6 (1.24)

5. Secondary Outcome

Title	Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group
Description	Serum amyloid A (SAA) were determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates.
Time Frame	at 72 hours and 7 days, 4 and 8 weeks post-dose

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients as randomized that had at least one post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Canakinumab 10 mg	Canakinumab 25 mg	Canakinumab 50 mg	Canakinumab 90 mg	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.
Measure Participants	28	29	28	29	27	56
72 hrs post-dose (n= 26, 28, 28, 28, 27, 50)	50.1 (20.05)	27.6 (19.32)	70.7 (19.37)	29.4 (19.28)	26.9 (19.69)	52.5 (14.48)
7 days post-dose (n= 28, 28, 28, 28, 26, 49)	10.6 (10.92)	5.4 (10.91)	11.9 (10.94)	10.5 (10.89)	10.3 (11.33)	39.4 (8.26)
4 week post-dose (n= 27, 28, 27, 28, 27, 50)	4.4 (3.53)	4.2 (3.46)	4.9 (3.53)	14.3 (3.45)	6.2 (3.53)	12.9 (2.59)
8 weeks post-dose (n= 26, 26, 26, 27, 27, 48)	5.5 (3.64)	4.6 (3.64)	5.7 (3.64)	8.2 (3.56)	4.1 (3.57)	18.0 (2.68)

6. Primary Outcome

Title	The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS)
Description	Mean target dose at 24, 48 and 72 hours. Four models: Emax, Logistic, Linear in log-dose, Linear were selected to describe the potential dose-response curve and hence estimate the target dose of canakinumab using baseline Visual Analog Scale (VAS) and Body Mass Index (BMI) as covariates. Target dose was defined as the dose for which the efficacy is equivalent to the efficacy of triamcinolone acetonide 40 mg and was identified by assessing the dose response relationship with regards to the pain intensity in the target joint measured on a 0- 100 mm VAS (0= no pain and 100= unbearable pain).
Time Frame	at 24,48 and 72 hours post-baseline

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Linear Model
Arm/Group Description	The linear model was the best-fitting model out of the 4 selected models (Emax, Logistic, Linear in Log-dose, Linear)with lowest Akaike Information Criterion (AIC).
Measure Participants	197
Target dose at 24 hrs post-baseline	37
Target dose at 48 hrs post-baseline	23
Target dose at 72 hrs post-baseline	NA

7. Secondary Outcome

Title	Amount of Rescue Medication Taken for Each Treatment Group
Description	Participants who had difficulty in tolerating their pain after the 6-hour post-dose pain assessments and during the first 7 study days were allowed to take a maximum of 30 mg prednisolone (or equivalent dose of prednisone [30 mg]) orally once a day for a maximum of 5 days. In addition, participants could use 500 mg acetaminophen (paracetamol) and/or 30 mg codeine as needed during the first 7 study days. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/dose or 180 mg/day of codeine was allowed during the first 7 days of the study.
Time Frame	7 days after study drug administration

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Canakinumab 10 mg	Canakinumab 25 mg	Canakinumab 50 mg	Canakinumab 90 mg	Canakinumab 150 mg	Triamcinolone Acetonide 40 mg
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.	Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.
Measure Participants	28	29	28	29	27	56
Acetaminophen	1414.3 (2628.58)	1656.9 (4437.26)	2178.6 (2925.67)	1646.6 (3161.20)	607.4 (2250.12)	1614.3 (2958.51)
Codeine	42.9 (138.19)	78.6 (164.20)	49.3 (139.57)	27.9 (87.07)	4.4 (23.09)	52.0 (158.28)
Prednisolone/Prednisone	13.4 (36.82)	23.8 (44.03)	24.1 (59.36)	13.1 (35.37)	6.2 (24.54)	13.3 (26.13)

Adverse Events

Time Frame	End of study (8 weeks)
Arm/Group Title	Canakinumab 10 mg		Canakinumab 25 mg		Canakinumab 50 mg		Canakinumab 90 mg		Canakinumab 150 mg		Triamcinolone Acetonide 40 mg
Arm/Group Description	Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.		Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.		Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.		Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.		Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.		Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1.
All Cause Mortality
	Canakinumab 10 mg		Canakinumab 25 mg		Canakinumab 50 mg		Canakinumab 90 mg		Canakinumab 150 mg		Triamcinolone Acetonide 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Canakinumab 10 mg		Canakinumab 25 mg		Canakinumab 50 mg		Canakinumab 90 mg		Canakinumab 150 mg		Triamcinolone Acetonide 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		2/29 (6.9%)		2/29 (6.9%)		0/29 (0%)		0/28 (0%)		1/57 (1.8%)
Infections and infestations
Appendicitis	0/28 (0%)		1/29 (3.4%)		1/29 (3.4%)		0/29 (0%)		0/28 (0%)		0/57 (0%)
Bronchitis	0/28 (0%)		1/29 (3.4%)		0/29 (0%)		0/29 (0%)		0/28 (0%)		0/57 (0%)
Nervous system disorders
Carotid artery stenosis	0/28 (0%)		0/29 (0%)		1/29 (3.4%)		0/29 (0%)		0/28 (0%)		0/57 (0%)
Cerebrovascular disorder	0/28 (0%)		0/29 (0%)		0/29 (0%)		0/29 (0%)		0/28 (0%)		1/57 (1.8%)
Other (Not Including Serious) Adverse Events
	Canakinumab 10 mg		Canakinumab 25 mg		Canakinumab 50 mg		Canakinumab 90 mg		Canakinumab 150 mg		Triamcinolone Acetonide 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/28 (7.1%)		7/29 (24.1%)		5/29 (17.2%)		8/29 (27.6%)		5/28 (17.9%)		8/57 (14%)
Infections and infestations
Nasopharyngitis	1/28 (3.6%)		1/29 (3.4%)		2/29 (6.9%)		0/29 (0%)		1/28 (3.6%)		2/57 (3.5%)
Urinary tract infection	0/28 (0%)		0/29 (0%)		0/29 (0%)		1/29 (3.4%)		0/28 (0%)		3/57 (5.3%)
Investigations
Alanine aminotransferase increased	0/28 (0%)		0/29 (0%)		0/29 (0%)		2/29 (6.9%)		0/28 (0%)		0/57 (0%)
Aspartate aminotransferase increased	0/28 (0%)		0/29 (0%)		0/29 (0%)		2/29 (6.9%)		1/28 (3.6%)		0/57 (0%)
Blood uric acid increased	0/28 (0%)		0/29 (0%)		0/29 (0%)		2/29 (6.9%)		1/28 (3.6%)		0/57 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	0/28 (0%)		0/29 (0%)		2/29 (6.9%)		0/29 (0%)		0/28 (0%)		0/57 (0%)
Pain in extremity	0/28 (0%)		1/29 (3.4%)		1/29 (3.4%)		0/29 (0%)		0/28 (0%)		3/57 (5.3%)
Nervous system disorders
Headache	1/28 (3.6%)		3/29 (10.3%)		1/29 (3.4%)		2/29 (6.9%)		1/28 (3.6%)		4/57 (7%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/28 (0%)		0/29 (0%)		0/29 (0%)		2/29 (6.9%)		1/28 (3.6%)		0/57 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/28 (0%)		2/29 (6.9%)		0/29 (0%)		0/29 (0%)		0/28 (0%)		0/57 (0%)

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.