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

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ClinicalTrials.gov Identifier: NCT00798369
Recruitment Status : Completed
First Posted : November 26, 2008
Results First Posted : May 16, 2011
Last Update Posted : April 10, 2012
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Acute Gout
Interventions Drug: Canakinumab
Drug: Triamcinolone acetonide
Enrollment 200
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Canakinumab 10 mg Canakinumab 25 mg Canakinumab 50 mg Canakinumab 90 mg Canakinumab 150 mg Triamcinolone Acetonide 40 mg
Hide 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
Reason Not Completed
Subject withdrew consent             0             0             1             1             0             2
Lost to Follow-up             1             1             1             0             1             0
Adminstrative problems             0             0             0             0             0             1
Arm/Group Title Canakinumab 10 mg Canakinumab 25 mg Canakinumab 50 mg Canakinumab 90 mg Canakinumab 150 mg Triamcinolone Acetonide 40 mg Total
Hide 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 Number of Baseline Participants 28 29 29 29 28 57 200
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 28 participants 29 participants 29 participants 29 participants 28 participants 57 participants 200 participants
≥18 years - 40 years 6 4 3 5 8 7 33
≥ 41 - 64 years 21 21 19 20 15 39 135
≥ 65 - 74 years 0 3 6 2 3 10 24
≥ 75 years 1 1 1 2 2 1 8
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 29 participants 29 participants 29 participants 28 participants 57 participants 200 participants
Female
2
   7.1%
3
  10.3%
2
   6.9%
5
  17.2%
0
   0.0%
2
   3.5%
14
   7.0%
Male
26
  92.9%
26
  89.7%
27
  93.1%
24
  82.8%
28
 100.0%
55
  96.5%
186
  93.0%
1.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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 197
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: mg
Target dose at 24 hrs post-baseline
37
(5.94 to 103.37)
Target dose at 48 hrs post-baseline
23
(2.87 to 96.31)
Target dose at 72 hrs post-baseline
NA [1] 
(NA to NA)
[1]
A target dose for canakinumab to be comparable to triamcinolone acetonide 40 mg could not be estimated at 72 hours as it lies below the range of all doses of canakinumab tested in this trial
2.Secondary Outcome
Title The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 28 29 28 29 27 56
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
3.Secondary Outcome
Title Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 28 29 28 29 27 56
Measure Type: Number
Unit of Measure: Percentage of Participants
64 62 71 66 89 54
4.Secondary Outcome
Title The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 28 29 28 29 27 56
Median (95% Confidence Interval)
Unit of Measure: Days
2.9
(1.0 to 4.0)
2.9
(2.0 to 3.0)
1.0
(1.0 to 2.9)
1.0
(1.0 to 2.0)
1.0
(0.5 to 2.0)
2.0
(1.0 to 3.6)
5.Secondary Outcome
Title High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 28 29 28 29 27 56
Least Squares Mean (Standard Error)
Unit of Measure: mg/L
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)
6.Secondary Outcome
Title Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 28 29 28 29 27 56
Least Squares Mean (Standard Error)
Unit of Measure: mg/L
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)
7.Secondary Outcome
Title Amount of Rescue Medication Taken for Each Treatment Group
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 28 29 28 29 27 56
Mean (Standard Deviation)
Unit of Measure: mg
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)
Time Frame End of study (8 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Canakinumab 10 mg Canakinumab 25 mg Canakinumab 50 mg Canakinumab 90 mg Canakinumab 150 mg Triamcinolone Acetonide 40 mg
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/28 (0.00%)   2/29 (6.90%)   2/29 (6.90%)   0/29 (0.00%)   0/28 (0.00%)   1/57 (1.75%) 
Infections and infestations             
Appendicitis  1  0/28 (0.00%)  1/29 (3.45%)  1/29 (3.45%)  0/29 (0.00%)  0/28 (0.00%)  0/57 (0.00%) 
Bronchitis  1  0/28 (0.00%)  1/29 (3.45%)  0/29 (0.00%)  0/29 (0.00%)  0/28 (0.00%)  0/57 (0.00%) 
Nervous system disorders             
Carotid artery stenosis  1  0/28 (0.00%)  0/29 (0.00%)  1/29 (3.45%)  0/29 (0.00%)  0/28 (0.00%)  0/57 (0.00%) 
Cerebrovascular disorder  1  0/28 (0.00%)  0/29 (0.00%)  0/29 (0.00%)  0/29 (0.00%)  0/28 (0.00%)  1/57 (1.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Canakinumab 10 mg Canakinumab 25 mg Canakinumab 50 mg Canakinumab 90 mg Canakinumab 150 mg Triamcinolone Acetonide 40 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/28 (7.14%)   7/29 (24.14%)   5/29 (17.24%)   8/29 (27.59%)   5/28 (17.86%)   8/57 (14.04%) 
Infections and infestations             
Nasopharyngitis  1  1/28 (3.57%)  1/29 (3.45%)  2/29 (6.90%)  0/29 (0.00%)  1/28 (3.57%)  2/57 (3.51%) 
Urinary tract infection  1  0/28 (0.00%)  0/29 (0.00%)  0/29 (0.00%)  1/29 (3.45%)  0/28 (0.00%)  3/57 (5.26%) 
Investigations             
Alanine aminotransferase increased  1  0/28 (0.00%)  0/29 (0.00%)  0/29 (0.00%)  2/29 (6.90%)  0/28 (0.00%)  0/57 (0.00%) 
Aspartate aminotransferase increased  1  0/28 (0.00%)  0/29 (0.00%)  0/29 (0.00%)  2/29 (6.90%)  1/28 (3.57%)  0/57 (0.00%) 
Blood uric acid increased  1  0/28 (0.00%)  0/29 (0.00%)  0/29 (0.00%)  2/29 (6.90%)  1/28 (3.57%)  0/57 (0.00%) 
Musculoskeletal and connective tissue disorders             
Bone pain  1  0/28 (0.00%)  0/29 (0.00%)  2/29 (6.90%)  0/29 (0.00%)  0/28 (0.00%)  0/57 (0.00%) 
Pain in extremity  1  0/28 (0.00%)  1/29 (3.45%)  1/29 (3.45%)  0/29 (0.00%)  0/28 (0.00%)  3/57 (5.26%) 
Nervous system disorders             
Headache  1  1/28 (3.57%)  3/29 (10.34%)  1/29 (3.45%)  2/29 (6.90%)  1/28 (3.57%)  4/57 (7.02%) 
Respiratory, thoracic and mediastinal disorders             
Oropharyngeal pain  1  0/28 (0.00%)  0/29 (0.00%)  0/29 (0.00%)  2/29 (6.90%)  1/28 (3.57%)  0/57 (0.00%) 
Skin and subcutaneous tissue disorders             
Hyperhidrosis  1  0/28 (0.00%)  2/29 (6.90%)  0/29 (0.00%)  0/29 (0.00%)  0/28 (0.00%)  0/57 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00798369     History of Changes
Other Study ID Numbers: CACZ885H2255
EudraCT 2008-004666-61
First Submitted: November 25, 2008
First Posted: November 26, 2008
Results First Submitted: January 20, 2011
Results First Posted: May 16, 2011
Last Update Posted: April 10, 2012