Trial Outcomes & Findings for A Study of the Efficacy of Canakinumab in Prevention of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy (Core Study) and a Long-term Study of the Efficacy and Safety of Canakinumab in Patients With Gout (Extension Study) (NCT NCT00819585)
NCT ID: NCT00819585
Last Updated: 2018-07-17
Results Overview
A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
432 participants
Primary outcome timeframe
Baseline of the core study to Week 16
Results posted on
2018-07-17
Participant Flow
A total of 432 participants were enrolled in the study.
Participant milestones
| Measure |
Core Study: Canakinumab 25 mg
Participants received canakinumab 25 mg subcutaneously (sc) on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 50 mg
Participants received canakinumab 50 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 100 mg
Participants received canakinumab 100 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 200 mg
Participants received canakinumab 200 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 300 mg
Participants received canakinumab 300 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab q4wk
Participants received canakinumab 50 mg sc on Days 1 and 29; canakinumab 25 mg sc on Days 57 and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Colchicine 0.5 mg
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
Extension Study: Group A
Participants who were randomized to canakinumab in the core study and were treated with canakinumab for at least 1 flare in the extension study.
|
Extension Study: Group B
Patients who were randomized to canakinumab in the core study but did not receive treatment with canakinumab in the extension study.
|
Extension Study: Group C
Patients who were randomized to colchicine in the core study and were treated with canakinumab for at least 1 flare in the extension study.
|
Extension Study: Group D
Patients who were randomized to colchicine in the core study but did not receive treatment with canakinumab in the extension study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Core Study
STARTED
|
55
|
54
|
54
|
54
|
53
|
54
|
108
|
0
|
0
|
0
|
0
|
|
Core Study
Received Study Medication
|
55
|
54
|
54
|
54
|
53
|
53
|
108
|
0
|
0
|
0
|
0
|
|
Core Study
COMPLETED
|
49
|
48
|
48
|
49
|
50
|
52
|
95
|
0
|
0
|
0
|
0
|
|
Core Study
NOT COMPLETED
|
6
|
6
|
6
|
5
|
3
|
2
|
13
|
0
|
0
|
0
|
0
|
|
Extension Study
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
75
|
181
|
25
|
60
|
|
Extension Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
75
|
173
|
24
|
58
|
|
Extension Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
8
|
1
|
2
|
Reasons for withdrawal
| Measure |
Core Study: Canakinumab 25 mg
Participants received canakinumab 25 mg subcutaneously (sc) on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 50 mg
Participants received canakinumab 50 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 100 mg
Participants received canakinumab 100 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 200 mg
Participants received canakinumab 200 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 300 mg
Participants received canakinumab 300 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab q4wk
Participants received canakinumab 50 mg sc on Days 1 and 29; canakinumab 25 mg sc on Days 57 and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Colchicine 0.5 mg
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
Extension Study: Group A
Participants who were randomized to canakinumab in the core study and were treated with canakinumab for at least 1 flare in the extension study.
|
Extension Study: Group B
Patients who were randomized to canakinumab in the core study but did not receive treatment with canakinumab in the extension study.
|
Extension Study: Group C
Patients who were randomized to colchicine in the core study and were treated with canakinumab for at least 1 flare in the extension study.
|
Extension Study: Group D
Patients who were randomized to colchicine in the core study but did not receive treatment with canakinumab in the extension study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Core Study
Adverse Event
|
2
|
1
|
1
|
4
|
1
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Core Study
Abnormal Laboratory Value(s)
|
2
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Core Study
Unsatisfactory Therapeutic Effect
|
0
|
1
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Core Study
Subject No Longer Requires Study Drug
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Core Study
Subject Withdrew Consent
|
0
|
3
|
2
|
1
|
0
|
0
|
3
|
0
|
0
|
0
|
0
|
|
Core Study
Lost to Follow-up
|
2
|
1
|
2
|
0
|
1
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Core Study
Administrative Problems
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Core Study
Death
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Core Study
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
1
|
3
|
0
|
0
|
0
|
0
|
|
Extension Study
Abnormal Laboratory Value(s)
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Extension Study
Subject Withdrew Consent
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
3
|
0
|
1
|
|
Extension Study
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
1
|
1
|
|
Extension Study
Death
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
Baseline Characteristics
A Study of the Efficacy of Canakinumab in Prevention of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy (Core Study) and a Long-term Study of the Efficacy and Safety of Canakinumab in Patients With Gout (Extension Study)
Baseline characteristics by cohort
| Measure |
Core Study: Canakinumab 25 mg
n=55 Participants
Participants received canakinumab 25 mg subcutaneously (sc) on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 50 mg
n=54 Participants
Participants received canakinumab 50 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 100 mg
n=54 Participants
Participants received canakinumab 100 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 200 mg
n=54 Participants
Participants received canakinumab 200 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab 300 mg
n=53 Participants
Participants received canakinumab 300 mg sc on Day 1; canakinumab placebo sc on Days 29, 57, and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Canakinumab q4wk
n=53 Participants
Participants received canakinumab 50 mg sc on Days 1 and 29; canakinumab 25 mg sc on Days 57 and 85; and colchicine placebo orally once daily for 16 weeks.
|
Core Study: Colchicine 0.5 mg
n=108 Participants
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
Total
n=431 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
50.7 Years
STANDARD_DEVIATION 9.72 • n=39 Participants
|
54.4 Years
STANDARD_DEVIATION 12.18 • n=41 Participants
|
51.3 Years
STANDARD_DEVIATION 12.41 • n=35 Participants
|
52.6 Years
STANDARD_DEVIATION 10.78 • n=31 Participants
|
52.4 Years
STANDARD_DEVIATION 11.30 • n=146 Participants
|
52.8 Years
STANDARD_DEVIATION 10.38 • n=19 Participants
|
52.4 Years
STANDARD_DEVIATION 10.69 • n=147 Participants
|
52.4 Years
STANDARD_DEVIATION 11.02 • n=193 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
4 Participants
n=31 Participants
|
2 Participants
n=146 Participants
|
4 Participants
n=19 Participants
|
7 Participants
n=147 Participants
|
26 Participants
n=193 Participants
|
|
Sex: Female, Male
Male
|
55 Participants
n=39 Participants
|
51 Participants
n=41 Participants
|
48 Participants
n=35 Participants
|
50 Participants
n=31 Participants
|
51 Participants
n=146 Participants
|
49 Participants
n=19 Participants
|
101 Participants
n=147 Participants
|
405 Participants
n=193 Participants
|
PRIMARY outcome
Timeframe: Baseline of the core study to Week 16Population: Full Analysis Set (FAS): All patients as randomized that had at least 1 post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.
A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
Outcome measures
| Measure |
Canakinumab 25 mg
n=55 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=54 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
n=54 Participants
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
n=54 Participants
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
n=53 Participants
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
n=54 Participants
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
n=108 Participants
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Core Study: Mean Number of Gout Flares Per Participant
|
0.5 Gout flares
Standard Deviation 1.03
|
0.4 Gout flares
Standard Deviation 1.82
|
0.2 Gout flares
Standard Deviation 0.53
|
0.4 Gout flares
Standard Deviation 1.35
|
0.2 Gout flares
Standard Deviation 0.53
|
0.7 Gout flares
Standard Deviation 2.24
|
0.7 Gout flares
Standard Deviation 1.00
|
SECONDARY outcome
Timeframe: up to 16 weeks after randomizationPopulation: The Full Analysis Set (FAS) consisted of all patients as randomized that had at least 1 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.
Outcome measures
| Measure |
Canakinumab 25 mg
n=55 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=54 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
n=54 Participants
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
n=54 Participants
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
n=53 Participants
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
n=54 Participants
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Core Study: Mean Number of Gout Flares for the Repeat Dose Regimen of Canakinumab as Compared to the Single Doses of Canakinumab
|
0.48 gout flares per patient
Standard Error 0.204
|
0.43 gout flares per patient
Standard Error 0.207
|
0.22 gout flares per patient
Standard Error 0.209
|
0.38 gout flares per patient
Standard Error 0.205
|
0.21 gout flares per patient
Standard Error 0.209
|
0.68 gout flares per patient
Standard Error 0.209
|
—
|
SECONDARY outcome
Timeframe: Baseline of the core study to Week 16Population: Full Analysis Set (FAS): All patients as randomized that had at least 1 post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.
The percentage of participants experiencing at least 1 gout flare within 16 weeks after randomization. A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
Outcome measures
| Measure |
Canakinumab 25 mg
n=55 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=54 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
n=54 Participants
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
n=54 Participants
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
n=53 Participants
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
n=54 Participants
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
n=108 Participants
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Core Study: Percentage of Participants With at Least 1 Gout Flare Within 16 Weeks After Randomization
|
27.3 Percentage of participants
|
16.7 Percentage of participants
|
14.8 Percentage of participants
|
18.5 Percentage of participants
|
15.1 Percentage of participants
|
16.7 Percentage of participants
|
44.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Days 2, 4, 6, and Weeks 2, 4, 6, 10, and 16 of the core studyPopulation: Full Analysis Set (FAS): All patients as randomized that had at least 1 post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.
A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
Outcome measures
| Measure |
Canakinumab 25 mg
n=55 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=54 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
n=54 Participants
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
n=54 Participants
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
n=53 Participants
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
n=54 Participants
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
n=108 Participants
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Core Study: Percentage of Participants With Gout Flare at Different Time Points
2 days post-dose
|
5.5 Percentage of participants
Interval 1.79 to 15.96
|
3.7 Percentage of participants
Interval 0.94 to 14.01
|
3.7 Percentage of participants
Interval 0.94 to 14.01
|
3.7 Percentage of participants
Interval 0.94 to 14.01
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
3.8 Percentage of participants
Interval 0.96 to 14.26
|
5.6 Percentage of participants
Interval 2.53 to 11.95
|
|
Core Study: Percentage of Participants With Gout Flare at Different Time Points
4 days post-dose
|
10.9 Percentage of participants
Interval 5.05 to 22.68
|
3.7 Percentage of participants
Interval 0.94 to 14.01
|
3.7 Percentage of participants
Interval 0.94 to 14.01
|
3.7 Percentage of participants
Interval 0.94 to 14.01
|
5.7 Percentage of participants
Interval 1.86 to 16.53
|
3.8 Percentage of participants
Interval 0.96 to 14.26
|
10.2 Percentage of participants
Interval 5.77 to 17.64
|
|
Core Study: Percentage of Participants With Gout Flare at Different Time Points
6 days post-dose
|
12.7 Percentage of participants
Interval 6.28 to 24.85
|
5.6 Percentage of participants
Interval 1.83 to 16.24
|
3.7 Percentage of participants
Interval 0.94 to 14.01
|
7.4 Percentage of participants
Interval 2.85 to 18.54
|
5.7 Percentage of participants
Interval 1.86 to 16.53
|
3.8 Percentage of participants
Interval 0.96 to 23.56
|
11.1 Percentage of participants
Interval 6.47 to 18.74
|
|
Core Study: Percentage of Participants With Gout Flare at Different Time Points
4 weeks post-dose
|
14.5 Percentage of participants
Interval 7.55 to 26.99
|
9.3 Percentage of participants
Interval 3.96 to 20.83
|
7.4 Percentage of participants
Interval 2.85 to 18.54
|
13.0 Percentage of participants
Interval 6.4 to 25.28
|
11.4 Percentage of participants
Interval 5.27 to 23.56
|
15.1 Percentage of participants
Interval 7.85 to 27.92
|
25.1 Percentage of participants
Interval 17.93 to 34.38
|
|
Core Study: Percentage of Participants With Gout Flare at Different Time Points
10 weeks post-dose
|
22.5 Percentage of participants
Interval 13.43 to 36.26
|
13.1 Percentage of participants
Interval 6.46 to 25.52
|
11.2 Percentage of participants
Interval 5.19 to 23.22
|
16.8 Percentage of participants
Interval 9.11 to 29.79
|
11.4 Percentage of participants
Interval 5.27 to 23.56
|
17.0 Percentage of participants
Interval 9.22 to 30.09
|
37.5 Percentage of participants
Interval 29.06 to 47.43
|
|
Core Study: Percentage of Participants With Gout Flare at Different Time Points
6 weeks post-dose
|
16.5 Percentage of participants
Interval 8.96 to 29.39
|
11.1 Percentage of participants
Interval 5.15 to 23.07
|
9.3 Percentage of participants
Interval 3.98 to 20.91
|
13.0 Percentage of participants
Interval 6.4 to 25.28
|
11.4 Percentage of participants
Interval 5.27 to 23.56
|
27.92 Percentage of participants
Interval 7.85 to 27.92
|
32.6 Percentage of participants
Interval 24.58 to 42.3
|
|
Core Study: Percentage of Participants With Gout Flare at Different Time Points
2 weeks post-dose
|
14.5 Percentage of participants
Interval 7.55 to 26.99
|
7.4 Percentage of participants
Interval 2.85 to 18.54
|
7.4 Percentage of participants
Interval 2.85 to 18.54
|
11.1 Percentage of participants
Interval 5.15 to 23.07
|
7.5 Percentage of participants
Interval 2.9 to 18.87
|
11.3 Percentage of participants
Interval 5.25 to 23.48
|
16.7 Percentage of participants
Interval 10.85 to 25.14
|
|
Core Study: Percentage of Participants With Gout Flare at Different Time Points
16 weeks post-dose
|
28.7 Percentage of participants
Interval 18.34 to 43.1
|
17.3 Percentage of participants
Interval 9.37 to 30.66
|
15.1 Percentage of participants
Interval 7.82 to 27.87
|
18.8 Percentage of participants
Interval 10.59 to 32.19
|
15.3 Percentage of participants
Interval 7.96 to 28.29
|
17.0 Percentage of participants
Interval 9.22 to 30.09
|
45.8 Percentage of participants
Interval 36.76 to 55.87
|
SECONDARY outcome
Timeframe: Baseline of the core study to Week 16Population: Full Analysis Set (FAS): All patients as randomized that had at least 1 post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.
Participants rated the intensity of pain in the most affected joint on a 0-100 mm visual analog scale, which ranged from no pain (left end, 0) to unbearable pain (right end, 100). Participants assessed pain intensity on the day of onset of the gout flare and in the morning of the 6 following days.
Outcome measures
| Measure |
Canakinumab 25 mg
n=55 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=54 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
n=54 Participants
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
n=54 Participants
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
n=53 Participants
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
n=54 Participants
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
n=108 Participants
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares
Day 6 (n=6, 1, 1, 2, 1, 3, 18)
|
19.6 Units on a scale
Standard Deviation 14.14
|
44.0 Units on a scale
Standard Deviation 0.0
|
0.0 Units on a scale
Standard Deviation 0.0
|
57.5 Units on a scale
Standard Deviation 60.10
|
12.0 Units on a scale
Standard Deviation 0.0
|
43.5 Units on a scale
Standard Deviation 24.38
|
33.7 Units on a scale
Standard Deviation 26.66
|
|
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares
Day 5 (n=7, 2, 1, 3, 2, 4, 22)
|
19.3 Units on a scale
Standard Deviation 14.79
|
48.0 Units on a scale
Standard Deviation 5.66
|
0.0 Units on a scale
Standard Deviation 0.0
|
54.8 Units on a scale
Standard Deviation 43.38
|
13.0 Units on a scale
Standard Deviation 0.0
|
41.4 Units on a scale
Standard Deviation 33.63
|
31.8 Units on a scale
Standard Deviation 29.91
|
|
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares
Day 1 (n=15, 9, 8, 9, 8, 9, 48)
|
41.1 Units on a scale
Standard Deviation 31.01
|
44.6 Units on a scale
Standard Deviation 15.82
|
56.3 Units on a scale
Standard Deviation 26.72
|
53.0 Units on a scale
Standard Deviation 27.99
|
52.2 Units on a scale
Standard Deviation 19.40
|
66.1 Units on a scale
Standard Deviation 15.07
|
53.1 Units on a scale
Standard Deviation 24.18
|
|
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares
Day 2 (n=12, 7, 6, 5, 5, 7, 44)
|
44.8 Units on a scale
Standard Deviation 30.06
|
40.1 Units on a scale
Standard Deviation 26.73
|
46.2 Units on a scale
Standard Deviation 35.11
|
19.8 Units on a scale
Standard Deviation 32.05
|
43.1 Units on a scale
Standard Deviation 17.62
|
59.3 Units on a scale
Standard Deviation 23.53
|
42.8 Units on a scale
Standard Deviation 24.37
|
|
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares
Day 3 (n=10, 4, 4, 4, 4, 5, 38)
|
31.5 Units on a scale
Standard Deviation 20.82
|
49.5 Units on a scale
Standard Deviation 18.48
|
49.5 Units on a scale
Standard Deviation 25.29
|
56.7 Units on a scale
Standard Deviation 40.91
|
26.3 Units on a scale
Standard Deviation 14.64
|
58.0 Units on a scale
Standard Deviation 27.59
|
38.1 Units on a scale
Standard Deviation 23.37
|
|
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares
Day 7 (n=6, 0, 1, 2, 1, 2, 16)
|
20.9 Units on a scale
Standard Deviation 16.91
|
NA Units on a scale
Standard Deviation NA
No data is available
|
0.0 Units on a scale
Standard Deviation 0.0
|
35.0 Units on a scale
Standard Deviation 49.50
|
0.0 Units on a scale
Standard Deviation 0.0
|
52.0 Units on a scale
Standard Deviation 11.31
|
33.0 Units on a scale
Standard Deviation 22.16
|
|
Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares
Day 4 (n=7, 3, 2, 3, 3, 6, 31)
|
31.8 Units on a scale
Standard Deviation 16.77
|
46.3 Units on a scale
Standard Deviation 10.60
|
16.5 Units on a scale
Standard Deviation 23.33
|
63.5 Units on a scale
Standard Deviation 33.0
|
11.0 Units on a scale
Standard Deviation 11.0
|
49.4 Units on a scale
Standard Deviation 27.73
|
30.5 Units on a scale
Standard Deviation 26.68
|
SECONDARY outcome
Timeframe: Baseline of the core study to Week 16Population: Full Analysis Set (FAS): All patients as randomized that had at least 1 post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.
Participants assessed the intensity of pain in the most affected joint on a 5-point Likert scale, which ranged from 1 to 5 (1=None, 2=Mild, 3=Moderate, 4=Severe, 5=Extreme). Participants assessed pain intensity on the day of onset of the gout flare and in the morning of the 6 following days.
Outcome measures
| Measure |
Canakinumab 25 mg
n=55 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=54 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
n=54 Participants
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
n=54 Participants
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
n=53 Participants
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
n=54 Participants
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
n=108 Participants
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares
Day 3 (n=10, 4, 4, 4, 4, 6, 38)
|
2.4 Units on a scale
Standard Deviation 0.73
|
3.1 Units on a scale
Standard Deviation 0.63
|
2.3 Units on a scale
Standard Deviation 0.96
|
3.0 Units on a scale
Standard Deviation 1.15
|
2.3 Units on a scale
Standard Deviation 0.50
|
3.4 Units on a scale
Standard Deviation 1.07
|
2.7 Units on a scale
Standard Deviation 0.76
|
|
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares
Day 4 (n=7, 3, 2, 3, 3, 7, 31)
|
2.6 Units on a scale
Standard Deviation 0.57
|
2.7 Units on a scale
Standard Deviation 0.58
|
1.5 Units on a scale
Standard Deviation 0.71
|
3.0 Units on a scale
Standard Deviation 1.00
|
1.7 Units on a scale
Standard Deviation 0.58
|
3.2 Units on a scale
Standard Deviation 1.08
|
2.4 Units on a scale
Standard Deviation 0.90
|
|
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares
Day 5 (n=7, 2, 1, 3, 2, 4, 22)
|
2.2 Units on a scale
Standard Deviation 0.69
|
2.5 Units on a scale
Standard Deviation 0.71
|
1.0 Units on a scale
Standard Deviation 0
|
3.2 Units on a scale
Standard Deviation 1.76
|
1.5 Units on a scale
Standard Deviation 0.71
|
2.7 Units on a scale
Standard Deviation 1.28
|
2.6 Units on a scale
Standard Deviation 0.95
|
|
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares
Day 1 (n=15, 8, 8, 9, 8, 9, 48)
|
2.8 Units on a scale
Standard Deviation 0.88
|
3.1 Units on a scale
Standard Deviation 0.65
|
3.5 Units on a scale
Standard Deviation 1.20
|
3.2 Units on a scale
Standard Deviation 0.92
|
3.1 Units on a scale
Standard Deviation 0.35
|
3.8 Units on a scale
Standard Deviation 0.60
|
3.2 Units on a scale
Standard Deviation 0.77
|
|
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares
Day 2 (n=12, 6, 6, 5, 5, 7, 44)
|
2.9 Units on a scale
Standard Deviation 0.92
|
2.6 Units on a scale
Standard Deviation 1.02
|
3.3 Units on a scale
Standard Deviation 1.51
|
2.2 Units on a scale
Standard Deviation 1.10
|
2.9 Units on a scale
Standard Deviation 0.74
|
3.5 Units on a scale
Standard Deviation 1.05
|
3.0 Units on a scale
Standard Deviation 0.86
|
|
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares
Day 6 (n=6, 1, 1, 2, 2, 3, 18)
|
2.4 Units on a scale
Standard Deviation 0.49
|
3.0 Units on a scale
Standard Deviation 0.0
|
1.0 Units on a scale
Standard Deviation 0.0
|
3.5 Units on a scale
Standard Deviation 2.12
|
1.5 Units on a scale
Standard Deviation 0.71
|
2.9 Units on a scale
Standard Deviation 0.84
|
2.5 Units on a scale
Standard Deviation 1.05
|
|
Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares
Day 7 (n=6, 0, 1, 2, 1, 2, 16)
|
2.4 Units on a scale
Standard Deviation 0.49
|
NA Units on a scale
Standard Deviation NA
No participants analyzed.
|
1.0 Units on a scale
Standard Deviation 0.0
|
2.5 Units on a scale
Standard Deviation 2.12
|
1.0 Units on a scale
Standard Deviation 0.0
|
3.3 Units on a scale
Standard Deviation 0.47
|
2.4 Units on a scale
Standard Deviation 0.81
|
SECONDARY outcome
Timeframe: Days 15, 29, 57, 85, 113, and 141 of the core studyPopulation: Full Analysis Set (FAS): All patients as randomized that had at least 1 post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.
The study physician made a global assessment of the participant's response to treatment on a 5-point Likert scale (Very good, Good, Fair, Poor, Very poor) at Days 15, 29, 57, 85, 113, and 141. The category 'Not assessed' includes missing data and 'not done'. The number of participants in each of the 5 categories of the Likert scale are reported.
Outcome measures
| Measure |
Canakinumab 25 mg
n=55 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=54 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
n=54 Participants
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
n=54 Participants
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
n=53 Participants
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
n=54 Participants
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
n=108 Participants
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 15 - Good
|
28 Participants
|
24 Participants
|
23 Participants
|
26 Participants
|
21 Participants
|
20 Participants
|
42 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 15 - Fair
|
5 Participants
|
4 Participants
|
3 Participants
|
4 Participants
|
0 Participants
|
3 Participants
|
16 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 15 - Poor
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
3 Participants
|
4 Participants
|
6 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 15 - Very poor
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 15 - Not assessed
|
3 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 29: Very good
|
26 Participants
|
24 Participants
|
25 Participants
|
24 Participants
|
27 Participants
|
27 Participants
|
39 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 29- Good
|
23 Participants
|
22 Participants
|
22 Participants
|
26 Participants
|
23 Participants
|
22 Participants
|
42 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 29 - Fair
|
2 Participants
|
4 Participants
|
5 Participants
|
3 Participants
|
2 Participants
|
2 Participants
|
19 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 29 - Poor
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 29 - Very poor
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 29 - Not assessed
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 57- Good
|
21 Participants
|
20 Participants
|
16 Participants
|
21 Participants
|
18 Participants
|
20 Participants
|
43 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 57 - Fair
|
5 Participants
|
3 Participants
|
6 Participants
|
4 Participants
|
4 Participants
|
3 Participants
|
9 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 57 - Poor
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
3 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 57 - Not assessed
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
4 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 85: Very good
|
27 Participants
|
31 Participants
|
32 Participants
|
32 Participants
|
31 Participants
|
29 Participants
|
43 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 85 - Good
|
20 Participants
|
17 Participants
|
15 Participants
|
16 Participants
|
17 Participants
|
17 Participants
|
41 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 85 - Fair
|
3 Participants
|
2 Participants
|
5 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
12 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 113 : Very good
|
24 Participants
|
29 Participants
|
30 Participants
|
26 Participants
|
29 Participants
|
32 Participants
|
50 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 113 - Very poor
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 113 - Not Assessed
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
8 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 141 - Good
|
16 Participants
|
20 Participants
|
19 Participants
|
12 Participants
|
14 Participants
|
14 Participants
|
36 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 141 - Poor
|
1 Participants
|
1 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 15: Very good
|
19 Participants
|
23 Participants
|
24 Participants
|
23 Participants
|
27 Participants
|
25 Participants
|
40 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 57: Very good
|
25 Participants
|
27 Participants
|
28 Participants
|
27 Participants
|
30 Participants
|
28 Participants
|
46 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 57 - Very poor
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 85 - - Poor
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 85 - Very poor
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 85 - Not assessed
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
5 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 113 - Good
|
18 Participants
|
18 Participants
|
18 Participants
|
20 Participants
|
20 Participants
|
15 Participants
|
36 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 113 - Fair
|
5 Participants
|
3 Participants
|
2 Participants
|
3 Participants
|
1 Participants
|
3 Participants
|
7 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 113 - Poor
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 141 : Very good
|
26 Participants
|
25 Participants
|
24 Participants
|
31 Participants
|
32 Participants
|
32 Participants
|
41 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 141 - Fair
|
6 Participants
|
2 Participants
|
3 Participants
|
6 Participants
|
2 Participants
|
3 Participants
|
16 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 141 - Very poor
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale
Day 141 - Not Assessed
|
0 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline of the extension study until 7 days after the onset of the first gout flare (up to 24 weeks)Population: Efficacy set: All Group A and C participants who received at least 1 dose of canakinumab during the extension study.
Participant's rated the intensity of pain in the most affected joint during the first flare on a 0-100 mm visual analog scale, which ranged from no pain (left end, 0) to unbearable pain (right end, 100). Assessments were made pre-dose and 24 hours, 3 days, 4 days, and an average of 5-7 days post-dose
Outcome measures
| Measure |
Canakinumab 25 mg
n=65 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=19 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare
24 hours (n=65, 18)
|
23.8 Units on a scale
Standard Deviation 23.32
|
29.0 Units on a scale
Standard Deviation 22.85
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare
3 days (n=54, 15)
|
12.4 Units on a scale
Standard Deviation 16.82
|
6.8 Units on a scale
Standard Deviation 9.03
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare
4 days (n=54, 15)
|
8.8 Units on a scale
Standard Deviation 14.32
|
2.7 Units on a scale
Standard Deviation 5.06
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare
Pre-dose (n=65, 19)
|
61.3 Units on a scale
Standard Deviation 27.13
|
71.8 Units on a scale
Standard Deviation 20.86
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare
5-7 days (n=52, 13)
|
8.1 Units on a scale
Standard Deviation 15.86
|
2.1 Units on a scale
Standard Deviation 4.70
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline of the extension study until the end of the study (up to 24 weeks)Population: Efficacy set: All Group A and C participants who received at least 1 dose of canakinumab during the extension study.
Study participants made a global assessment of their response to treatment on a 5-point Likert scale (Excellent, Good, Acceptable, Slight, Poor) at the control visit 7±2 days following each of their first 3 flares. The number of participants in each of the 5 categories of the Likert scale are reported.
Outcome measures
| Measure |
Canakinumab 25 mg
n=63 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=21 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Slight (63, 21)
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Poor (63, 21)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Slight (3, 1)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Excellent (63, 21)
|
40 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Good (63, 21)
|
17 Participants
|
14 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Acceptable (63, 21)
|
5 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Excellent (11, 5)
|
4 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Good (11, 5)
|
6 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Acceptable (11, 5)
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Slight (11, 5)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Poor (11, 5)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Excellent (3, 1)
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Good (3, 1)
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Acceptable (3, 1)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Poor (3, 1)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline of the extension study until the end of the study (up to 24 weeks)Population: Efficacy set: All Group A and C participants who received at least 1 dose of canakinumab during the extension study.
The study physician made a global assessment of the participant's response to treatment on a 5-point Likert scale (Very good, Good, Fair, Poor, Very poor) at the control visit 7±2 days following each of the first 3 flares. The category 'Not assessed' includes missing data and 'not done'. The number of participants in each of the 5 categories of the Likert scale are reported.
Outcome measures
| Measure |
Canakinumab 25 mg
n=69 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=23 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Good (69, 23)
|
28 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Very Good (12, 5)
|
5 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Good (12, 5)
|
7 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Fair (12, 5)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Good (3, 1)
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Very Good (69, 23)
|
37 Participants
|
13 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Fair (69, 23)
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Poor (69, 23)
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 1: Very Poor (69, 23)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Poor (12, 5)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 2: Very Poor (12, 5)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Very Good (3, 1)
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Fair (3, 1)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Poor (3, 1)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale
Gout Flare 3: Very Poor (3, 1)
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline of the extension study until the end of the study (up to 24 weeks)Population: Efficacy set: All Group A and C participants who received at least 1 dose of canakinumab during the extension study.
Tenderness was rated on a 0-3 point scale: 0="no pain", 1=patient states that "there is pain", 2=patient states "there is pain and winces", and 3=patient states "there is pain, winces and withdraws" on palpation or passive movement of the most affected joint. Swelling was rated on a 0-3 point scale: 0="no swelling", 1="palpable", 2="visible", and 3=bulging beyond the joint margins". Erythema was rated as present, absent, or not assessable. Assessments were performed at the flare and control visits.
Outcome measures
| Measure |
Canakinumab 25 mg
n=69 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=24 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Tenderness Flare Visit: Pain and winces
|
23 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Tenderness Flare Visit: Pain, winces and withdraws
|
17 Participants
|
12 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Tenderness Control Visit: Pain
|
8 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Tenderness Control Visit: Pain and winces
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Tenderness Control Visit: Pain, winces and withdra
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Erythema Control Visit: Not assessed
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Erythema Control Visit: Absent
|
66 Participants
|
24 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Erythema Flare Visit: Not assessed
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Erythema Control Visit: Present
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Tenderness Flare Visit: No pain
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Tenderness Flare Visit: Pain
|
27 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Tenderness Control Visit: No pain
|
60 Participants
|
21 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Joint Swelling Flare Visit: No swelling
|
5 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Joint Swelling Flare Visit: Palpable
|
20 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Joint Swelling Flare Visit: Visible
|
31 Participants
|
17 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Joint Swelling Flare Visit: Bulging beyond joint
|
13 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Joint Swelling Control Visit: No swelling
|
61 Participants
|
22 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Joint Swelling Control Visit: Palpable
|
6 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Joint Swelling Control Visit: Visible
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Joint Swelling Control Visit: Bulging beyond joint
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Erythema Flare Visit: Absent
|
21 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare
Erythema Flare Visit: Present
|
44 Participants
|
20 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline of the extension study until the end of the study (up to 24 weeks)Population: Efficacy set: All Group A and C participants who received at least 1 dose of canakinumab during the extension study.
The amount of naproxen and prednisolone taken after receiving treatment for each of the first 3 flares was recorded.
Outcome measures
| Measure |
Canakinumab 25 mg
n=68 Participants
Canakinumab 25 mg subcutaneously (s.c.) once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 50 mg
n=24 Participants
Canakinumab 50 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 100 mg
Canakinumab 100 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 200 mg
Canakinumab 200 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab 300 mg
Canakinumab 300 mg s.c. once at Day 1, placebo s.c. at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Canakinumab q4wk
Canakinumab 50 mg s.c. at Days 1, and 29 followed by canakinumab 25 mg s.c. on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg- 300 mg) for 24 weeks.
|
Core Study: Colchicine 0.5 mg
Participants received colchicine 0.5 mg orally once daily for 16 weeks and canakinumab placebo sc on Days 1, 29, 57, and 85.
|
|---|---|---|---|---|---|---|---|
|
Extension Study: Amount of Rescue Medication Taken
Gout Flare 1: Naproxen (n=68, 24)
|
1086.8 mg
Standard Deviation 1592.72
|
954.6 mg
Standard Deviation 1130.19
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Amount of Rescue Medication Taken
Gout Flare 1: Prednisolone (68, 24)
|
4.6 mg
Standard Deviation 20.84
|
4.2 mg
Standard Deviation 20.41
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Amount of Rescue Medication Taken
Gout Flare 2: Naproxen (n=12, 5)
|
650.0 mg
Standard Deviation 642.79
|
200.0 mg
Standard Deviation 447.21
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Amount of Rescue Medication Taken
Gout Flare 2: Prednisolone (12, 5)
|
1.3 mg
Standard Deviation 3.11
|
0.0 mg
Standard Deviation 0.00
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Amount of Rescue Medication Taken
Gout Flare 3: Naproxen (n=4, 1)
|
250.0 mg
Standard Deviation 500.00
|
0.0 mg
Standard Deviation 0.00
|
—
|
—
|
—
|
—
|
—
|
|
Extension Study: Amount of Rescue Medication Taken
Gout Flare 3: Prednisolone (4, 1)
|
0.0 mg
Standard Deviation 0.00
|
0.0 mg
Standard Deviation 0.00
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Core Study: ACZ 25 mg
Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths
Core Study: ACZ 50 mg
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
Core Study: ACZ 100 mg
Serious events: 3 serious events
Other events: 14 other events
Deaths: 0 deaths
Core Study: ACZ 200 mg
Serious events: 3 serious events
Other events: 14 other events
Deaths: 0 deaths
Core Study: ACZ 300 mg
Serious events: 3 serious events
Other events: 15 other events
Deaths: 0 deaths
Core Study: ACZ Q4wk mg
Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths
Core Study: Colch 0.5 mg
Serious events: 6 serious events
Other events: 21 other events
Deaths: 0 deaths
Extension Study: Group A
Serious events: 4 serious events
Other events: 21 other events
Deaths: 0 deaths
Extension Study: Group B
Serious events: 6 serious events
Other events: 19 other events
Deaths: 0 deaths
Extension Study: Group C
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Extension Study: Group D
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Core Study: ACZ 25 mg
n=55 participants at risk
Core study: ACZ 25 mg
|
Core Study: ACZ 50 mg
n=54 participants at risk
Core study: ACZ 50 mg
|
Core Study: ACZ 100 mg
n=54 participants at risk
Core study: ACZ 100 mg
|
Core Study: ACZ 200 mg
n=54 participants at risk
Core study: ACZ 200 mg
|
Core Study: ACZ 300 mg
n=53 participants at risk
Core study: ACZ 300 mg
|
Core Study: ACZ Q4wk mg
n=53 participants at risk
Core study: ACZ Q4wk mg
|
Core Study: Colch 0.5 mg
n=108 participants at risk
Core study: Colch 0.5 mg
|
Extension Study: Group A
n=75 participants at risk
Extension study: Group A
|
Extension Study: Group B
n=181 participants at risk
Extension study: Group B
|
Extension Study: Group C
n=25 participants at risk
Extension study: Group C
|
Extension Study: Group D
n=60 participants at risk
Extension study: Group D
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Cardiac disorders
Myocardial fibrosis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.00%
0/55
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
1.3%
1/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
1.3%
1/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Infections and infestations
Ear infection
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
1.9%
1/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Infections and infestations
Erysipelas
|
1.8%
1/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Infections and infestations
Gangrene
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Infections and infestations
Pneumonia
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
1.9%
1/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Infections and infestations
Sepsis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Gun shot wound
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Heat exhaustion
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
1.7%
1/60
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
1.8%
1/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Gouty tophus
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
1.3%
1/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/55
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Nervous system disorders
Stupor
|
0.00%
0/55
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/55
|
0.00%
0/54
|
1.9%
1/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/55
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
1.3%
1/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
0.00%
0/53
|
0.00%
0/108
|
1.3%
1/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
Other adverse events
| Measure |
Core Study: ACZ 25 mg
n=55 participants at risk
Core study: ACZ 25 mg
|
Core Study: ACZ 50 mg
n=54 participants at risk
Core study: ACZ 50 mg
|
Core Study: ACZ 100 mg
n=54 participants at risk
Core study: ACZ 100 mg
|
Core Study: ACZ 200 mg
n=54 participants at risk
Core study: ACZ 200 mg
|
Core Study: ACZ 300 mg
n=53 participants at risk
Core study: ACZ 300 mg
|
Core Study: ACZ Q4wk mg
n=53 participants at risk
Core study: ACZ Q4wk mg
|
Core Study: Colch 0.5 mg
n=108 participants at risk
Core study: Colch 0.5 mg
|
Extension Study: Group A
n=75 participants at risk
Extension study: Group A
|
Extension Study: Group B
n=181 participants at risk
Extension study: Group B
|
Extension Study: Group C
n=25 participants at risk
Extension study: Group C
|
Extension Study: Group D
n=60 participants at risk
Extension study: Group D
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.5%
3/55
|
1.9%
1/54
|
3.7%
2/54
|
5.6%
3/54
|
1.9%
1/53
|
0.00%
0/53
|
1.9%
2/108
|
2.7%
2/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Gastrointestinal disorders
Nausea
|
3.6%
2/55
|
1.9%
1/54
|
5.6%
3/54
|
0.00%
0/54
|
0.00%
0/53
|
1.9%
1/53
|
0.93%
1/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Infections and infestations
Nasopharyngitis
|
9.1%
5/55
|
3.7%
2/54
|
3.7%
2/54
|
0.00%
0/54
|
0.00%
0/53
|
5.7%
3/53
|
0.93%
1/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
3.3%
2/60
|
|
Infections and infestations
Upper respiratory tract infection
|
3.6%
2/55
|
1.9%
1/54
|
3.7%
2/54
|
5.6%
3/54
|
1.9%
1/53
|
5.7%
3/53
|
3.7%
4/108
|
6.7%
5/75
|
2.2%
4/181
|
4.0%
1/25
|
0.00%
0/60
|
|
Investigations
Alanine aminotransferase increased
|
5.5%
3/55
|
1.9%
1/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Investigations
Aspartate aminotransferase increased
|
5.5%
3/55
|
1.9%
1/54
|
0.00%
0/54
|
1.9%
1/54
|
0.00%
0/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.55%
1/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
3.7%
2/54
|
1.9%
1/53
|
0.00%
0/53
|
0.00%
0/108
|
0.00%
0/75
|
0.55%
1/181
|
8.0%
2/25
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.3%
4/55
|
9.3%
5/54
|
7.4%
4/54
|
3.7%
2/54
|
5.7%
3/53
|
3.8%
2/53
|
2.8%
3/108
|
5.3%
4/75
|
3.3%
6/181
|
0.00%
0/25
|
1.7%
1/60
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.5%
3/55
|
5.6%
3/54
|
1.9%
1/54
|
5.6%
3/54
|
0.00%
0/53
|
0.00%
0/53
|
3.7%
4/108
|
1.3%
1/75
|
1.1%
2/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Nervous system disorders
Headache
|
7.3%
4/55
|
5.6%
3/54
|
1.9%
1/54
|
3.7%
2/54
|
11.3%
6/53
|
5.7%
3/53
|
5.6%
6/108
|
4.0%
3/75
|
1.1%
2/181
|
4.0%
1/25
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/55
|
1.9%
1/54
|
3.7%
2/54
|
3.7%
2/54
|
1.9%
1/53
|
0.00%
0/53
|
0.00%
0/108
|
5.3%
4/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/55
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/54
|
5.7%
3/53
|
0.00%
0/53
|
0.93%
1/108
|
0.00%
0/75
|
0.00%
0/181
|
0.00%
0/25
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.8%
1/55
|
1.9%
1/54
|
0.00%
0/54
|
0.00%
0/54
|
0.00%
0/53
|
5.7%
3/53
|
0.93%
1/108
|
1.3%
1/75
|
0.00%
0/181
|
0.00%
0/25
|
1.7%
1/60
|
|
Vascular disorders
Hypertension
|
10.9%
6/55
|
3.7%
2/54
|
3.7%
2/54
|
9.3%
5/54
|
7.5%
4/53
|
3.8%
2/53
|
0.93%
1/108
|
8.0%
6/75
|
1.7%
3/181
|
8.0%
2/25
|
0.00%
0/60
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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 (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER