Trial Outcomes & Findings for Study of the Efficacy and Safety of Secukinumab in Participants With Active Psoriatic Arthritis With Axial Skeleton Involvement (NCT NCT02721966)

NCT ID: NCT02721966

Last Updated: 2020-10-01

Results Overview

Purpose of this measure: was to demonstrate that secukinumab 150 mg s.c. is superior to placebo in the achievement of ASAS 20 response at Week 12 after superiority of 300 mg was established ASAS20 was defined as an improvement of ≥20% and absolute improvement of ≥10 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

503 participants

Primary outcome timeframe

at week 12

Results posted on

2020-10-01

Participant Flow

503 participants completed the screening period; and the randomized set consists of 498 patients because 5 participants were misrandomized

95.6% of those randomized completed period 1 and moved on to period 2; and the 85.3% completed treatment period 2.

Participant milestones

Participant milestones
Measure	AIN457 300mg Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	AIN457 150mg Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 300 mg Placebo sc injection weekly for 4 weeks and at week 8, followed by Secukinumab 300 mg sc injection every 4 week for remaining 40 weeks.	Placebo AIN457 150 mg Placebo sc injection weekly for 4 weeks and at week 8, followed by Secukinumab 150 mg sc injection every 4 week for remaining 40 weeks.	Placebo Placebo sc injections at baseline and weekly until Week 8
Overall Study STARTED	167	165	81	80	5
Overall Study Completed Period 1 & Went to Period 2	162	153	81	80	0
Overall Study COMPLETED	138	142	72	73	0
Overall Study NOT COMPLETED	29	23	9	7	5

Reasons for withdrawal

Reasons for withdrawal
Measure	AIN457 300mg Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	AIN457 150mg Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 300 mg Placebo sc injection weekly for 4 weeks and at week 8, followed by Secukinumab 300 mg sc injection every 4 week for remaining 40 weeks.	Placebo AIN457 150 mg Placebo sc injection weekly for 4 weeks and at week 8, followed by Secukinumab 150 mg sc injection every 4 week for remaining 40 weeks.	Placebo Placebo sc injections at baseline and weekly until Week 8
Overall Study Protocol Violation	1	0	0	0	0
Overall Study Withdrawal by Subject	9	2	3	7	0
Overall Study Adverse Event	4	4	3	0	0
Overall Study Death	1	0	0	0	0
Overall Study Lack of Efficacy	7	4	0	0	0
Overall Study Lost to Follow-up	0	0	3	0	0
Overall Study Physician Decision	1	1	0	0	0
Overall Study Pregnancy	1	0	0	0	0
Overall Study Did not continue to period 2	5	12	0	0	5

Baseline Characteristics

Study of the Efficacy and Safety of Secukinumab in Participants With Active Psoriatic Arthritis With Axial Skeleton Involvement

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AIN457 300mg n=167 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	AIN457 150mg n=165 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=166 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48	Total n=498 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	159 Participants n=5 Participants	156 Participants n=7 Participants	157 Participants n=5 Participants	472 Participants n=4 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	26 Participants n=4 Participants
Age, Customized <45 years old	77 Participants n=5 Participants	65 Participants n=7 Participants	72 Participants n=5 Participants	214 Participants n=4 Participants
Age, Customized >=45 years old	90 Participants n=5 Participants	100 Participants n=7 Participants	94 Participants n=5 Participants	284 Participants n=4 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	84 Participants n=7 Participants	78 Participants n=5 Participants	252 Participants n=4 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	81 Participants n=7 Participants	88 Participants n=5 Participants	246 Participants n=4 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	162 Participants n=5 Participants	159 Participants n=7 Participants	164 Participants n=5 Participants	485 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	5 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	6 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	139 Participants n=5 Participants	140 Participants n=7 Participants	146 Participants n=5 Participants	425 Participants n=4 Participants
Race/Ethnicity, Customized Not reported	17 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	35 Participants n=4 Participants

PRIMARY outcome

Timeframe: at week 12

Population: Full analysis set (FAS)

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Percentage of Participants With Response to Treatment (300 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12	66.3 percentage of participants Interval 58.4 to 73.3	62.9 percentage of participants Interval 55.2 to 70.0	31.2 percentage of participants Interval 24.6 to 38.7

SECONDARY outcome

Timeframe: at week 12

Population: Full analysis set (FAS)

Purpose of this key secondary measure: was to demonstrate that secukinumab 150 mg s.c. is superior to placebo in the achievement of ASAS 20 response at Week 12 after superiority of 300 mg was established. 300mg and 150mg are presented side by side for clarity; and to align with protocol. 300mg data is for Primary outcome; and 150mg data is for key secondary outcome ASAS20 was defined as an improvement of ≥20% and absolute improvement of ≥10 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI)

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Percentage of Participants With Response to Treatment (150 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12	66.3 percentage of participants Interval 58.4 to 73.3	62.9 percentage of participants Interval 55.2 to 70.0	31.2 percentage of participants Interval 24.6 to 38.7

SECONDARY outcome

Timeframe: at week 12

Population: Full analysis set (FAS)

Proportion of patients with response to treatment as assessed by the Assessment of spondyloarthritis international society (ASAS) 40 criteria at week 12. ASAS40 was defined as an improvement of ≥40% and absolute improvement of ≥20 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI)

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Percentage of Participants With Response to Treatment (150 mg/300 mg AIN457) as Assessed by the ASAS40 Criteria at Week 12	39.5 percentage of participants Interval 32.1 to 47.4	43.6 percentage of participants Interval 36.2 to 51.3	12.2 percentage of participants Interval 7.8 to 18.4

SECONDARY outcome

Timeframe: at week 12

Population: FAS

Bath ankylosing spondylitis disease activity index (BASDAI) 50 response BASDAI 50 response is defined as at least 50% improvement (decrease) in total BASDAI score.

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Percentage of Participants With Response to Treatment as Assessed by BASDAI50 at Week 12	32.7 percentage of particiapnts Interval 25.8 to 40.5	37.4 percentage of particiapnts Interval 30.1 to 45.4	9.8 percentage of particiapnts Interval 5.9 to 15.6

SECONDARY outcome

Timeframe: at baseline, at week 12

Population: FAS

Change from baseline in Spinal pain visual analog scale (VAS) at week 12 VAS is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptom,pain,health) orientated from the left (worst) to the right (best). VAS measures pain and stress for on a horizontal line of 100 mm, ranging from very low (0) to very high (100).

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Any Time	-28.5 scores on a scale Standard Error 1.88	-26.5 scores on a scale Standard Error 1.84	-13.6 scores on a scale Standard Error 1.83

SECONDARY outcome

Timeframe: at baseline, at week 12

Population: FAS

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Night	-30.3 scores on a scale Standard Error 1.95	-30.2 scores on a scale Standard Error 1.90	-15.2 scores on a scale Standard Error 1.89

SECONDARY outcome

Timeframe: baseline and week 12

Population: FAS

The Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index score range is 0-16, where 0 is the best outcome, and 16 the worst. The assessor determines whether the site shows tenderness and therefore would count as site with enthesitis. This is done by applying pressure to the site and getting feedback from patient about whether the site is tender.

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Change From Baseline Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index Score at Week 12	-2.2 scores on a scale Standard Error 0.22	-2.4 scores on a scale Standard Error 0.21	-1.7 scores on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: baseline and week 12

Population: FAS

The health assessment questionnaire disability index (HAQ-DI) assesses the difficulty a patient has had in the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question, level of difficulty is scored from 0 to 3 with 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. The score for each domain is the maximum (worst) score from the items/questions within the domain. Higher score indicates greater disability. Overall score was computed as the sum of the domain scores divided by the number of domains answered. The total possible score ranged from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability.

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12	-0.330 scores on a scale Standard Error 0.0360	-0.389 scores on a scale Standard Error 0.0353	-0.155 scores on a scale Standard Error 0.0351

SECONDARY outcome

Timeframe: baseline and week 12

Population: FAS

The FACIT-fatigue scale is a 13-item patient-reported measure of fatigue with a 7-day recall period. Items are scored on a 0 - 4 response scale with anchors ranging from "Not at all" to "Very much so". To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52.

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 12	8.0 scores on a scale Standard Error 0.72	7.6 scores on a scale Standard Error 0.71	4.2 scores on a scale Standard Error 0.70

SECONDARY outcome

Timeframe: baseline and week 12

Population: Full analysis set (FAS)

Statistical analysis (using ANCOVA) of change from baseline in spondyloarthritis international society (ASAS) Health Index score by visit - treatment period 1 ASAS HI is a disease-specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17-item instrument has scores ranging from 0 (good health) to 17 (poor health). Each item consists of one question that the participant needs to respond to with either "I agree" (score of 1) or "I do not agree" (score of 0). A score of "1" is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Change From Baseline in Spondyloarthritis International Society (ASAS) Health Index at Week 12	-2.9 scores on a scale Standard Error 0.29	-2.8 scores on a scale Standard Error 0.28	-1.2 scores on a scale Standard Error 0.28

SECONDARY outcome

Timeframe: at week 12

Population: Full analysis set (FAS)

American College of Rheumatology 20% (ACR20) Response at Week 12 is the % of responders with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)

Outcome measures

Outcome measures
Measure	AIN457 150mg n=157 Participants Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48	AIN457 300mg n=164 Participants Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48	Placebo AIN457 n=164 Participants Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48
Percentage of Participants With Response to Treatment as Assessed by the ACR20 Criteria at Week 12	56.5 percentage of participants Interval 47.5 to 65.1	51.6 percentage of participants Interval 43.4 to 59.8	18.5 percentage of participants Interval 13.1 to 25.5

Adverse Events

Secukinumab 300 mg

Serious events: 14 serious events

Other events: 116 other events

Deaths: 1 deaths

Secukinumab 150 mg

Serious events: 14 serious events

Other events: 108 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharma AG

Phone: 1-888-669-6682

Email: [email protected]

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. Publications from a single-site are postponed until publication of the pooled clinical trial data (i.e., data from all sites) or disclosure of trial results in their entirety
Publication restrictions are in place

Restriction type: OTHER

Measure	Secukinumab 300 mg n=248 participants at risk Secukinumab 300 mg sc. injections at baseline and weekly until Week 4 followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48 and placebo-switchers to Secukinumab at week 12 onwards	Secukinumab 150 mg n=245 participants at risk Secukinumab 150 mg sc. injections at baseline and weekly until Week 4 followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48 and placebo-switchers to Secukinumab at week 12 onwards	Placebo n=166 participants at risk Placebo sc. injections at baseline and weekly until Week 4, then at Week 8
Gastrointestinal disorders Diarrhoea	6.5% 16/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.9% 7/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 4/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Gastrointestinal disorders Vomiting	2.0% 5/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.2% 3/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.60% 1/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
General disorders Fatigue	2.4% 6/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.2% 3/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 4/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Bronchitis	4.4% 11/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	3.7% 9/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.60% 1/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Ear infection	2.0% 5/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.82% 2/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.00% 0/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Gastroenteritis	2.0% 5/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.6% 4/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.2% 2/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Nasopharyngitis	13.7% 34/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	9.0% 22/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	6.6% 11/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Pharyngitis	2.8% 7/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	5.3% 13/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	3.0% 5/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Rhinitis	3.6% 9/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.0% 5/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.00% 0/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Sinusitis	1.6% 4/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 6/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.00% 0/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Tonsillitis	2.8% 7/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.2% 3/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.00% 0/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Upper respiratory tract infection	4.8% 12/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	5.7% 14/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	3.0% 5/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Urinary tract infection	3.2% 8/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	4.5% 11/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.2% 2/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Infections and infestations Viral upper respiratory tract infection	0.40% 1/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 6/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.60% 1/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Investigations Blood creatinine increased	3.2% 8/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 6/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.00% 0/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Investigations Hepatic enzyme increased	2.0% 5/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.00% 0/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.00% 0/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 5/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.9% 7/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	3.0% 5/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Musculoskeletal and connective tissue disorders Back pain	3.6% 9/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 6/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	3.6% 6/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	1.6% 4/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.9% 7/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.60% 1/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Nervous system disorders Headache	2.8% 7/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.9% 7/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	3.6% 6/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Nervous system disorders Sciatica	0.40% 1/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 6/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.2% 2/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Respiratory, thoracic and mediastinal disorders Cough	2.8% 7/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 6/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.8% 3/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.0% 5/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	3.7% 9/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 4/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Skin and subcutaneous tissue disorders Erythema	0.00% 0/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.0% 5/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.00% 0/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Skin and subcutaneous tissue disorders Pruritus	2.0% 5/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.82% 2/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	0.60% 1/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Skin and subcutaneous tissue disorders Psoriasis	2.0% 5/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	2.4% 6/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.2% 2/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment
Vascular disorders Hypertension	1.6% 4/248 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	4.1% 10/245 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment	1.2% 2/166 • Adverse events were collected from first dose of study treatment until end of study at week 12 An Adverse Event (AE) is any untoward sign or symptom that occurs during the study treatment