Trial Outcomes & Findings for To Determine the Safety, Tolerability, Pharmacokinetics and Effect on Pain of a Single Intra-articular Administration of Canakinumab in Patients With Osteoarthritis in the Knee (NCT NCT01160822)

NCT ID: NCT01160822

Last Updated: 2012-10-30

Results Overview

An intolerance event is defined as an acute inflammatory reaction, characterized by a 30 mm increase in pain (on a 100 mm visual analog scale (VAS) and associated with a new or worsened synovial fluid effusion within 3 days following the intra-articular (i.a.) injection. If baseline VAS pain score is ≥ 70 mm, an intolerance event is defined as an increase in pain by 20 mm on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection. If baseline VAS pain score is ≥ 80 mm, an intolerance event is defined as an increase in pain by 10 mm on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection. If baseline pain score is ≥ 90 mm, an intolerance event is defined as the patients experiencing an unspecified increase in pain on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 169 participants
• Primary outcome timeframe: Baseline to Day 3
• Results posted on: 2012-10-30

Participant Flow

Participant milestones

Measure	Part A: Canakinumab 150 mg Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.	Part B: Canakinumab Participants received a single intra-articular injection of 600 mg canakinumab on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Placebo Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Naproxen Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen 500mg tablets orally twice daily for 12 weeks.
Overall Study STARTED	6	7	6	5	45	47	53
Overall Study COMPLETED	6	7	6	5	36	40	44
Overall Study NOT COMPLETED	0	0	0	0	9	7	9

Reasons for withdrawal

Measure	Part A: Canakinumab 150 mg Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.	Part B: Canakinumab Participants received a single intra-articular injection of 600 mg canakinumab on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Placebo Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Naproxen Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen 500mg tablets orally twice daily for 12 weeks.
Overall Study Adverse Event	0	0	0	0	1	2	5
Overall Study Unsatisfactory therapeutic effect	0	0	0	0	4	5	3
Overall Study Withdrawal by Subject	0	0	0	0	0	0	1
Overall Study Lost to Follow-up	0	0	0	0	1	0	0
Overall Study Administrative problems	0	0	0	0	1	0	0
Overall Study Protocol deviation	0	0	0	0	2	0	0

Baseline Characteristics

To Determine the Safety, Tolerability, Pharmacokinetics and Effect on Pain of a Single Intra-articular Administration of Canakinumab in Patients With Osteoarthritis in the Knee

Baseline characteristics by cohort

Measure	Part A: Canakinumab 150 mg n=6 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=7 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=6 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=5 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.	Part B: Canakinumab n=45 Participants Participants received a single intra-articular injection of 600 mg canakinumab on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Placebo n=47 Participants Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Naproxen n=53 Participants Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen 500mg tablets orally twice daily for 12 weeks.	Total n=169 Participants Total of all reporting groups
Age Continuous	58.3 years STANDARD_DEVIATION 12.79 • n=5 Participants	61.0 years STANDARD_DEVIATION 9.63 • n=7 Participants	64.2 years STANDARD_DEVIATION 10.68 • n=5 Participants	57.8 years STANDARD_DEVIATION 7.76 • n=4 Participants	NA years STANDARD_DEVIATION NA • n=21 Participants	NA years STANDARD_DEVIATION NA • n=8 Participants	NA years STANDARD_DEVIATION NA • n=8 Participants	60.5 years STANDARD_DEVIATION 10.07 • n=24 Participants
Age, Customized	NA years STANDARD_DEVIATION NA • n=5 Participants	NA years STANDARD_DEVIATION NA • n=7 Participants	NA years STANDARD_DEVIATION NA • n=5 Participants	NA years STANDARD_DEVIATION NA • n=4 Participants	61.4 years STANDARD_DEVIATION 8.96 • n=21 Participants	60.3 years STANDARD_DEVIATION 9.71 • n=8 Participants	62.2 years STANDARD_DEVIATION 8.10 • n=8 Participants	61.3 years STANDARD_DEVIATION 8.89 • n=24 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	31 Participants n=21 Participants	31 Participants n=8 Participants	34 Participants n=8 Participants	107 Participants n=24 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	14 Participants n=21 Participants	16 Participants n=8 Participants	19 Participants n=8 Participants	62 Participants n=24 Participants

PRIMARY outcome

Timeframe: Baseline to Day 3

Population: Safety analysis set.

An intolerance event is defined as an acute inflammatory reaction, characterized by a 30 mm increase in pain (on a 100 mm visual analog scale (VAS) and associated with a new or worsened synovial fluid effusion within 3 days following the intra-articular (i.a.) injection. If baseline VAS pain score is ≥ 70 mm, an intolerance event is defined as an increase in pain by 20 mm on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection. If baseline VAS pain score is ≥ 80 mm, an intolerance event is defined as an increase in pain by 10 mm on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection. If baseline pain score is ≥ 90 mm, an intolerance event is defined as the patients experiencing an unspecified increase in pain on a 100 mm VAS associated with new or worsened synovial fluid effusion within 3 days following the i.a. injection.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=6 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=7 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=6 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=5 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.
Part A: Number of Participants With Intolerance Events	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline and Day 4

Population: Pharmacodynamic (PD) analysis set - Patients with any available PD data and no major protocol deviations with impact on PD data, and where data were available.

After walking for 20 meters, participants were asked to assess the pain in their affected knee on a 100 mm linear visual analog scale ranging from no pain (0 mm) to unbearable pain (100 mm). A negative change from Baseline score indicates improvement.

Results are from a Bayesian analysis of covariance (ANCOVA) model, fitting baseline pain VAS score as a covariate, time by treatment as fixed effects, region and subject as random effects.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=42 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=44 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=49 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Change From Baseline to Day 4 in Pain Using 100 mm Visual Analog Scale (VAS)	-26.7 units on a scale Standard Deviation 4.05	-26.5 units on a scale Standard Deviation 3.97	-27.6 units on a scale Standard Deviation 3.82	—

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: Pharmacodynamic (PD) analysis set - Patients with any available PD data and no major protocol deviations with impact on PD data, and where data were available.

The Western Ontario and McMaster osteoarthritis Index (WOMAC) pain subscale asks patients to rate pain in the index knee joint in the last 48 hours doing different activities on a scale from none (0) to extreme pain (4). The answers are summed and the total pain subscale score ranges from 0 to 20, where higher scores indicate more pain. A negative change from Baseline score indicates improvement.

Results are from a Bayesian ANCOVA model, fitting baseline WOMAC pain score as a covariate, time by treatment as fixed effects, region and patient as random effects.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=42 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=44 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=48 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Change From Baseline to Week 4 in Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain Subscale	-3.5 units on a scale Standard Deviation 0.71	-4.0 units on a scale Standard Deviation 0.68	-4.5 units on a scale Standard Deviation 0.65	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: Pharmacodynamic (PD) analysis set - Patients with any available PD data and no major protocol deviations with impact on PD data.

After walking for 20 meters, participants were asked to assess the pain in their affected knee on a 100 mm linear visual analog scale ranging from no pain (0 mm) to unbearable pain (100 mm).

Results are from a Bayesian ANCOVA model, fitting baseline pain VAS score as a covariate, time by treatment as fixed effects, region and patient as random effects.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=43 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=44 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=49 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Change From Baseline in Pain Using 100 mm Visual Analog Scale (VAS) Week 12	-25.1 units on a scale Standard Deviation 4.14	-32.1 units on a scale Standard Deviation 4.06	-27.8 units on a scale Standard Deviation 3.94	—
Part B: Change From Baseline in Pain Using 100 mm Visual Analog Scale (VAS) Week 4	-25.6 units on a scale Standard Deviation 4.03	-31.1 units on a scale Standard Deviation 4.03	-36.1 units on a scale Standard Deviation 3.84	—
Part B: Change From Baseline in Pain Using 100 mm Visual Analog Scale (VAS) Week 8	-26.2 units on a scale Standard Deviation 4.12	-30.9 units on a scale Standard Deviation 4.06	-33.0 units on a scale Standard Deviation 3.89	—

SECONDARY outcome

Timeframe: Baseline, Day 4, Weeks 1, 2, 4, 8 and 12

Population: Pharmacodynamic (PD) analysis set - Patients with any available PD data and no major protocol deviations with impact on PD data. N is the number of participants with available data at each time point.

A responder is defined as a participant with a 50% or greater reduction from baseline on the VAS scale for pain assessment. After walking for 20 meters, participants were asked to assess the pain in their affected knee on a 100 mm linear visual analog scale ranging from no pain (0 mm) to unbearable pain (100 mm).

Outcome measures

Measure	Part A: Canakinumab 150 mg n=43 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=44 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=49 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Percentage of Responders in the Pain 100 mm Visual Analog Scale (VAS) Day 4 [N=42, 44, 48]	50.0 percentage of participants	43.2 percentage of participants	47.9 percentage of participants	—
Part B: Percentage of Responders in the Pain 100 mm Visual Analog Scale (VAS) Week 1 [N=42, 44, 48]	40.5 percentage of participants	45.5 percentage of participants	56.3 percentage of participants	—
Part B: Percentage of Responders in the Pain 100 mm Visual Analog Scale (VAS) Week 2 [N=41, 44, 48]	46.3 percentage of participants	43.2 percentage of participants	62.5 percentage of participants	—
Part B: Percentage of Responders in the Pain 100 mm Visual Analog Scale (VAS) Week 4 [N=39, 40, 46]	51.3 percentage of participants	55.0 percentage of participants	71.7 percentage of participants	—
Part B: Percentage of Responders in the Pain 100 mm Visual Analog Scale (VAS) Week 8 [N=36, 38, 43]	52.8 percentage of participants	50.0 percentage of participants	55.8 percentage of participants	—
Part B: Percentage of Responders in the Pain 100 mm Visual Analog Scale (VAS) Week 12 [N=35, 37, 41]	48.6 percentage of participants	51.4 percentage of participants	53.7 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: Pharmacodynamic (PD) analysis set - Patients with any available PD data and no major protocol deviations with impact on PD data.

The WOMAC consists of 3 subscales:

The Pain subscale asks patients to rate pain in the index knee joint in the last 48 hours during walking, using stairs, in bed, sitting or lying, and standing on a scale from none (0) to extreme pain (4). The answers are summed and the total pain subscale score ranges from 0-20.

The Stiffness subscale assesses stiffness in the index knee joint during the last 48 hours doing different activities on a scale from none (0) to extreme stiffness (4). The total stiffness subscale score ranges from 0-8.

The Physical Function subscale assesses difficulty performing daily physical activities during the last 48 hours on a scale from none (0) to extreme difficulty (4). The total physical function subscale score ranges from 0-68.

Higher scores indicate more pain/stiffness/difficulty. Results are from a Bayesian ANCOVA model, with baseline WOMAC score as a covariate, time by treatment as fixed effects, region and patient as random effects.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=43 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=44 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=49 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales Stiffness at Week 12	-1.1 units on a scale Standard Deviation 0.37	-1.7 units on a scale Standard Deviation 0.37	-1.4 units on a scale Standard Deviation 0.35	—
Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales Function at Week 4 [N=38, 39, 43]	-14.1 units on a scale Standard Deviation 1.93	-15.9 units on a scale Standard Deviation 1.93	-16.2 units on a scale Standard Deviation 1.76	—
Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales Function at Week 8 [N=35, 36, 41]	-13.7 units on a scale Standard Deviation 1.97	-14.9 units on a scale Standard Deviation 1.94	-16.1 units on a scale Standard Deviation 1.77	—
Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales Function at Week 12 [N= 33, 36, 39]	-13.4 units on a scale Standard Deviation 2.01	-16.5 units on a scale Standard Deviation 1.96	-14.4 units on a scale Standard Deviation 1.80	—
Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales Pain at Week 8	-3.7 units on a scale Standard Deviation 0.72	-4.2 units on a scale Standard Deviation 0.69	-4.6 units on a scale Standard Deviation 0.66	—
Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales Pain at Week 12	-3.2 units on a scale Standard Deviation 0.72	-4.5 units on a scale Standard Deviation 0.69	-4.0 units on a scale Standard Deviation 0.66	—
Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales Stiffness at Week 4	-1.3 units on a scale Standard Deviation 0.36	-1.5 units on a scale Standard Deviation 0.36	-1.9 units on a scale Standard Deviation 0.34	—
Part B: Change From Baseline in WOMAC Pain, Stiffness and Physical Function Subscales Stiffness at Week 8	-1.3 units on a scale Standard Deviation 0.37	-1.5 units on a scale Standard Deviation 0.36	-2.0 units on a scale Standard Deviation 0.35	—

SECONDARY outcome

Timeframe: Day 4, Weeks 1, 2, 4, 8 and 12

Population: Safety analysis set (all participants as assigned that received at least one dose of study drug).

Participants were permitted to take oral rescue medication (Acetaminophen ≤ 4 gram/day) up until 24 hours of a scheduled assessment visit during the 12-week treatment period. The estimates shown are the Kaplan-Meier estimates of the proportion of participants that took rescue medication.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=45 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=47 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=53 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Proportion of Participants Who Used Rescue Analgesic During Study Week 2	0.52 proportion of participants	0.57 proportion of participants	0.33 proportion of participants	—
Part B: Proportion of Participants Who Used Rescue Analgesic During Study Week 4	0.55 proportion of participants	0.60 proportion of participants	0.43 proportion of participants	—
Part B: Proportion of Participants Who Used Rescue Analgesic During Study Day 4	0.27 proportion of participants	0.30 proportion of participants	0.19 proportion of participants	—
Part B: Proportion of Participants Who Used Rescue Analgesic During Study Week 8	0.57 proportion of participants	0.69 proportion of participants	0.59 proportion of participants	—
Part B: Proportion of Participants Who Used Rescue Analgesic During Study Week 12	0.62 proportion of participants	0.75 proportion of participants	0.70 proportion of participants	—
Part B: Proportion of Participants Who Used Rescue Analgesic During Study Week 1	0.45 proportion of participants	0.47 proportion of participants	0.23 proportion of participants	—

SECONDARY outcome

Timeframe: Day 4

Population: Pharmacodynamic analysis set, where data were available.

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

Outcome measures

Measure	Part A: Canakinumab 150 mg n=42 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=44 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=48 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Patient's Global Assessment of Response to Treatment on Day 4 Excellent	6 participants	8 participants	4 participants	—
Patient's Global Assessment of Response to Treatment on Day 4 Good	14 participants	16 participants	20 participants	—
Patient's Global Assessment of Response to Treatment on Day 4 Poor	5 participants	5 participants	6 participants	—
Patient's Global Assessment of Response to Treatment on Day 4 Very poor	6 participants	2 participants	2 participants	—
Patient's Global Assessment of Response to Treatment on Day 4 Acceptable	11 participants	13 participants	16 participants	—

SECONDARY outcome

Timeframe: Week 2

Population: Pharmacodynamic analysis set, where data were available.

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

Outcome measures

Measure	Part A: Canakinumab 150 mg n=41 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=43 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=48 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Patient's Global Assessment of Response to Treatment at Week 2 Excellent	5 participants	6 participants	11 participants	—
Patient's Global Assessment of Response to Treatment at Week 2 Good	12 participants	16 participants	19 participants	—
Patient's Global Assessment of Response to Treatment at Week 2 Acceptable	13 participants	14 participants	12 participants	—
Patient's Global Assessment of Response to Treatment at Week 2 Poor	9 participants	5 participants	5 participants	—
Patient's Global Assessment of Response to Treatment at Week 2 Very poor	2 participants	2 participants	1 participants	—

SECONDARY outcome

Timeframe: Week 4

Population: Pharmacodynamic analysis set, where data were available.

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

Outcome measures

Measure	Part A: Canakinumab 150 mg n=39 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=40 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=46 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Patient's Global Assessment of Response to Treatment at Week 4 Excellent	5 participants	6 participants	9 participants	—
Patient's Global Assessment of Response to Treatment at Week 4 Good	15 participants	16 participants	18 participants	—
Patient's Global Assessment of Response to Treatment at Week 4 Acceptable	10 participants	10 participants	13 participants	—
Patient's Global Assessment of Response to Treatment at Week 4 Poor	8 participants	6 participants	4 participants	—
Patient's Global Assessment of Response to Treatment at Week 4 Very poor	1 participants	2 participants	2 participants	—

SECONDARY outcome

Timeframe: Week 8

Population: Pharmacodynamic analysis set, where data were available.

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

Outcome measures

Measure	Part A: Canakinumab 150 mg n=36 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=38 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=43 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Patient's Global Assessment of Response to Treatment at Week 8 Good	9 participants	19 participants	18 participants	—
Patient's Global Assessment of Response to Treatment at Week 8 Acceptable	11 participants	8 participants	9 participants	—
Patient's Global Assessment of Response to Treatment at Week 8 Poor	9 participants	5 participants	5 participants	—
Patient's Global Assessment of Response to Treatment at Week 8 Very poor	2 participants	1 participants	1 participants	—
Patient's Global Assessment of Response to Treatment at Week 8 Excellent	5 participants	5 participants	10 participants	—

SECONDARY outcome

Timeframe: Week 12

Population: Pharmacodynamic analysis set, where data were available.

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

Outcome measures

Measure	Part A: Canakinumab 150 mg n=35 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=37 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=41 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Patient's Global Assessment of Response to Treatment at Week 12 Excellent	4 participants	8 participants	7 participants	—
Patient's Global Assessment of Response to Treatment at Week 12 Good	12 participants	13 participants	15 participants	—
Patient's Global Assessment of Response to Treatment at Week 12 Acceptable	7 participants	14 participants	13 participants	—
Patient's Global Assessment of Response to Treatment at Week 12 Poor	11 participants	2 participants	5 participants	—
Patient's Global Assessment of Response to Treatment at Week 12 Very poor	1 participants	0 participants	1 participants	—

SECONDARY outcome

Timeframe: Day 4

Population: Pharmacodynamic analysis set, where data were available.

The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=42 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=44 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=48 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Physician's Global Assessment of Response to Treatment at Day 4 Good	11 participants	18 participants	21 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Day 4 Acceptable	16 participants	14 participants	13 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Day 4 Poor	4 participants	3 participants	7 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Day 4 Very poor	3 participants	2 participants	1 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Day 4 Excellent	8 participants	7 participants	6 participants	—

SECONDARY outcome

Timeframe: Week 2

Population: Pharmacodynamic analysis set, where data were available.

The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=40 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=44 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=48 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Physician's Global Assessment of Response to Treatment at Week 2 Excellent	7 participants	5 participants	15 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 2 Good	15 participants	20 participants	20 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 2 Acceptable	10 participants	13 participants	9 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 2 Poor	6 participants	4 participants	4 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 2 Very poor	2 participants	2 participants	0 participants	—

SECONDARY outcome

Timeframe: Week 4

Population: Pharmacodynamic analysis set, where data were available.

The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=39 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=40 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=46 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Physician's Global Assessment of Response to Treatment at Week 4 Poor	5 participants	3 participants	4 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 4 Very poor	1 participants	1 participants	0 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 4 Excellent	4 participants	5 participants	9 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 4 Good	15 participants	20 participants	21 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 4 Acceptable	14 participants	11 participants	12 participants	—

SECONDARY outcome

Timeframe: Week 8

Population: Pharmacodynamic analysis set, where data were available.

The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=36 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=38 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=43 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Physician's Global Assessment of Response to Treatment at Week 8 Excellent	5 participants	3 participants	9 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 8 Acceptable	10 participants	11 participants	13 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 8 Poor	7 participants	2 participants	5 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 8 Very poor	1 participants	0 participants	0 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 8 Good	13 participants	22 participants	16 participants	—

SECONDARY outcome

Timeframe: Week 12

Population: Pharmacodynamic analysis set, where data were available.

The study physician made a global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Poor, Very Poor.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=35 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=37 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=41 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo Participants received a single intra-articular injection of canakinumab-matching placebo.
Part B: Physician's Global Assessment of Response to Treatment at Week 12 Excellent	5 participants	7 participants	10 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 12 Good	13 participants	16 participants	15 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 12 Acceptable	6 participants	12 participants	8 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 12 Poor	9 participants	2 participants	7 participants	—
Part B: Physician's Global Assessment of Response to Treatment at Week 12 Very poor	2 participants	0 participants	1 participants	—

SECONDARY outcome

Timeframe: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

Population: Pharmacokinetic analysis set where data were available.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=6 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=6 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=6 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=39 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.
Maximum Observed Plasma Concentration of Canakinumab (Cmax)	23.0 µg/mL Standard Deviation 8.54	34.8 µg/mL Standard Deviation 11.3	65.5 µg/mL Standard Deviation 14.5	77.8 µg/mL Standard Deviation 22.8

SECONDARY outcome

Timeframe: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

Population: Pharmacokinetic analysis set where data were available.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=6 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=6 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=6 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=39 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.
Time to Reach the Maximum Observed Plasma Concentration of Canakinumab (Tmax)	96.2 hours Interval 74.6 to 164.0	86.7 hours Interval 71.8 to 174.0	144 hours Interval 71.5 to 197.0	95.9 hours Interval 46.3 to 335.0

SECONDARY outcome

Timeframe: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

Population: Pharmacokinetic analysis set where data were available.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=6 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=6 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=6 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=35 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.
Area Under the Concentration Time Curve up to the Last Measurable Concentration (AUClast)	16900 µg*day/mL Standard Deviation 4430	30700 µg*day/mL Standard Deviation 8380	56100 µg*day/mL Standard Deviation 23900	71900 µg*day/mL Standard Deviation 23800

SECONDARY outcome

Timeframe: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

Population: Pharmacokinetic analysis set where data were available.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=5 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=6 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=5 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=33 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.
Area Under the Concentration Time Curve From Time Zero to Infinity AUC(0-inf)	16900 µg*day/mL Standard Deviation 4780	32400 µg*day/mL Standard Deviation 8010	49300 µg*day/mL Standard Deviation 16100	78300 µg*day/mL Standard Deviation 28000

SECONDARY outcome

Timeframe: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

Population: Pharmacokinetic analysis set where data were available.

The time it takes for the concentration level of canakinumab to fall to 50% of the original value.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=5 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=6 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=5 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=34 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.
Terminal Phase Half-life (t1/2) of Canakinumab	539 hours Standard Deviation 47.1	578 hours Standard Deviation 145	474 hours Standard Deviation 93.6	736 hours Standard Deviation 243

SECONDARY outcome

Timeframe: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

Population: Pharmacokinetic analysis set, where data were available.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=5 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=6 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=5 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=33 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.
Apparent Clearance of Canakinumab From Plasma (CL/F)	9.58 mL/hr Standard Deviation 3.08	9.66 mL/hr Standard Deviation 2.03	13.3 mL/hr Standard Deviation 4.27	8.65 mL/hr Standard Deviation 3.02

SECONDARY outcome

Timeframe: Day 1, pre-dose and 1, 3, 6 and 8 hours post-dose (Part A only), Day 2, 4, 8, 15, 29, 57, 85 and 126.

Population: Pharmacokinetic analysis set, where data were available.

Outcome measures

Measure	Part A: Canakinumab 150 mg n=5 Participants Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=6 Participants Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=5 Participants Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=33 Participants Participants received a single intra-articular injection of canakinumab-matching placebo.
Apparent Volume of Distribution During Terminal Phase (Vz/F)	7320 mL Standard Deviation 1870	8060 mL Standard Deviation 2830	8930 mL Standard Deviation 3000	8910 mL Standard Deviation 4070

Adverse Events

Part A: Canakinumab 150 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part A: Canakinumab 300 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part A: Canakinumab 600 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Part B: Canakinumab

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Part B: Placebo

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

Part B: Naproxen

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A: Canakinumab 150 mg n=6 participants at risk Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=7 participants at risk Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=6 participants at risk Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=5 participants at risk Participants received a single intra-articular injection of canakinumab-matching placebo.	Part B: Canakinumab n=45 participants at risk Participants received a single intra-articular injection of 600 mg canakinumab on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Placebo n=47 participants at risk Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Naproxen n=53 participants at risk Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen 500mg tablets orally twice daily for 12 weeks.
Cardiac disorders Myocardial infarction	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	2.1% 1/47	0.00% 0/53
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	1.9% 1/53
General disorders Non-cardiac chest pain	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	2.1% 1/47	0.00% 0/53
Infections and infestations Cellulitis	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Infections and infestations Diverticulitis	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	2.1% 1/47	0.00% 0/53
Infections and infestations Influenza	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	1.9% 1/53
Infections and infestations Tooth infection	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	1.9% 1/53
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	1.9% 1/53
Metabolism and nutrition disorders Dehydration	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Nervous system disorders Cerebrovascular accident	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	2.1% 1/47	0.00% 0/53
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	1.9% 1/53
Vascular disorders Orthostatic hypotension	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	0.00% 0/53

Other adverse events

Measure	Part A: Canakinumab 150 mg n=6 participants at risk Participants received a single intra-articular injection of 150 mg canakinumab.	Part A: Canakinumab 300 mg n=7 participants at risk Participants received a single intra-articular injection of 300 mg canakinumab.	Part A: Canakinumab 600 mg n=6 participants at risk Participants received a single intra-articular injection of 600 mg canakinumab.	Part A: Placebo n=5 participants at risk Participants received a single intra-articular injection of canakinumab-matching placebo.	Part B: Canakinumab n=45 participants at risk Participants received a single intra-articular injection of 600 mg canakinumab on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Placebo n=47 participants at risk Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen matching placebo tablets orally twice daily for 12 weeks.	Part B: Naproxen n=53 participants at risk Participants received a single intra-articular injection of canakinumab matching placebo on Day 1 and naproxen 500mg tablets orally twice daily for 12 weeks.
Ear and labyrinth disorders Cerumen impaction	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Eye disorders Retinal tear	0.00% 0/6	14.3% 1/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	0.00% 0/45	2.1% 1/47	3.8% 2/53
Gastrointestinal disorders Diarrhoea	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	6.7% 3/45	8.5% 4/47	3.8% 2/53
Gastrointestinal disorders Dyspepsia	0.00% 0/6	14.3% 1/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	5.7% 3/53
Gastrointestinal disorders Nausea	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	0.00% 0/45	8.5% 4/47	3.8% 2/53
Gastrointestinal disorders Vomiting	0.00% 0/6	14.3% 1/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	2.1% 1/47	1.9% 1/53
General disorders Chest discomfort	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
General disorders Fatigue	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	1.9% 1/53
General disorders Pain	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	1.9% 1/53
Infections and infestations Bronchitis	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	4.4% 2/45	0.00% 0/47	5.7% 3/53
Infections and infestations Cellulitis	0.00% 0/6	28.6% 2/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Infections and infestations Gastroenteritis viral	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	5.7% 3/53
Infections and infestations Influenza	0.00% 0/6	14.3% 1/7	0.00% 0/6	0.00% 0/5	4.4% 2/45	8.5% 4/47	3.8% 2/53
Infections and infestations Nasopharyngitis	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	6.7% 3/45	4.3% 2/47	13.2% 7/53
Infections and infestations Sinusitis	0.00% 0/6	14.3% 1/7	0.00% 0/6	20.0% 1/5	2.2% 1/45	2.1% 1/47	1.9% 1/53
Infections and infestations Staphylococcal infection	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Infections and infestations Tooth abscess	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Infections and infestations Upper respiratory tract infection	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	2.2% 1/45	2.1% 1/47	0.00% 0/53
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Injury, poisoning and procedural complications Arthropod sting	16.7% 1/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Injury, poisoning and procedural complications Contusion	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	2.1% 1/47	5.7% 3/53
Injury, poisoning and procedural complications Excoriation	16.7% 1/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Metabolism and nutrition disorders Fluid retention	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Metabolism and nutrition disorders Hypokalaemia	16.7% 1/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6	28.6% 2/7	16.7% 1/6	0.00% 0/5	8.9% 4/45	12.8% 6/47	5.7% 3/53
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	2.2% 1/45	2.1% 1/47	7.5% 4/53
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	2.2% 1/45	0.00% 0/47	0.00% 0/53
Musculoskeletal and connective tissue disorders Neuropathic arthropathy	0.00% 0/6	14.3% 1/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	7.5% 4/53
Nervous system disorders Dizziness	0.00% 0/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	6.4% 3/47	3.8% 2/53
Nervous system disorders Headache	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	11.1% 5/45	12.8% 6/47	3.8% 2/53
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	16.7% 1/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	3.8% 2/53
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	2.2% 1/45	6.4% 3/47	1.9% 1/53
Skin and subcutaneous tissue disorders Dermatitis	16.7% 1/6	0.00% 0/7	0.00% 0/6	0.00% 0/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Skin and subcutaneous tissue disorders Seborrhoea	0.00% 0/6	0.00% 0/7	0.00% 0/6	20.0% 1/5	0.00% 0/45	0.00% 0/47	0.00% 0/53
Vascular disorders Hypertension	0.00% 0/6	0.00% 0/7	16.7% 1/6	0.00% 0/5	0.00% 0/45	4.3% 2/47	1.9% 1/53

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 (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER