Trial Outcomes & Findings for Study of Power Doppler Ultrasound (PDUS) to Measure Response of Secukinumab Treatment in Patients With Active Psoriatic Arthritis (PsA) (NCT NCT02662985)

Last Updated: 2021-12-07

Results Overview

Mixed model repeated measures (MMRM) analysis of change in Global OMERACT-EULAR Synovitis Score (GLOESS) score at Week 12 (observed data) to compare treatments The range for the GLOESS score is 0 to 144. GLOESS is the ultrasound scoring system measured for 24 pairs of joints. The scoring is from 0 to 3 for each joint; so the minimum score can be 0 and maximum can be 144.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

166 participants

Primary outcome timeframe

12 weeks

Results posted on

2021-12-07

Participant Flow

166 participants enrolled in 17 countries

83 partcipants were randomized to each group

Participant milestones

Participant milestones
Measure	Group 1 - Secukinumab (150 mg + 300 mg) In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Group 2 - Placebo/Secukinumab In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label 150 or 300 mg secukinumab every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients
Treatment Period 1 STARTED	83	83
Treatment Period 1 COMPLETED	82	79
Treatment Period 1 NOT COMPLETED	1	4
Treatment Period 2 STARTED	82	79
Treatment Period 2 COMPLETED	81	78
Treatment Period 2 NOT COMPLETED	1	1
Treatment Period 3 (Extension Period) STARTED	81	78
Treatment Period 3 (Extension Period) COMPLETED	75	69
Treatment Period 3 (Extension Period) NOT COMPLETED	6	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1 - Secukinumab (150 mg + 300 mg) In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Group 2 - Placebo/Secukinumab In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label 150 or 300 mg secukinumab every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients
Treatment Period 1 Adverse Event	0	2
Treatment Period 1 Protocol Violation	0	1
Treatment Period 1 Physician Decision	1	0
Treatment Period 1 Withdrawal by Subject	0	1
Treatment Period 2 Lack of Efficacy	0	1
Treatment Period 2 Lost to Follow-up	1	0
Treatment Period 3 (Extension Period) Withdrew before entering period	4	4
Treatment Period 3 (Extension Period) Adverse Event	1	1
Treatment Period 3 (Extension Period) Lack of Efficacy	0	1
Treatment Period 3 (Extension Period) Withdrawal by Subject	1	2
Treatment Period 3 (Extension Period) Death	0	1

Baseline Characteristics

Study of Power Doppler Ultrasound (PDUS) to Measure Response of Secukinumab Treatment in Patients With Active Psoriatic Arthritis (PsA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 - Secukinumab (150 mg + 300 mg) n=83 Participants In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Group 2 - Placebo/Secukinumab (150 mg + 300 mg) n=83 Participants In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label secukinumab 150 or 300 mg every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients	Total n=166 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
Age, Categorical Between 18 and 65 years	76 Participants n=5 Participants	79 Participants n=7 Participants	155 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	46.7 years STANDARD_DEVIATION 12.35 • n=5 Participants	46.7 years STANDARD_DEVIATION 12.08 • n=7 Participants	46.7 years STANDARD_DEVIATION 12.18 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	46 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	37 Participants n=7 Participants	75 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	75 Participants n=5 Participants	75 Participants n=7 Participants	150 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native American	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Full analysis set (FAS): The FAS comprised all patients from the Randomized set to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	Group 1 - Secukinumab (150 mg + 300 mg) n=83 Participants In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Group 2 - Placebo/Secukinumab n=81 Participants In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label 150 or 300 mg secukinumab every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients
Difference Between Secukinumab and Placebo in Terms of Joint Synovitis as Measured by the Power Doppler Ultrasonography (PDUS) Global OMERACT-EULAR Synovitis Score (GLOESS)	-9.05 Adjusted Mean Change in scores Standard Error 0.94	-5.86 Adjusted Mean Change in scores Standard Error 0.93

SECONDARY outcome

Timeframe: Week 12

Population: Full Analysis Set (FAS)

ACR 20 responder has ≥ 20% improvement in TJC and SJC and \>20% improvement in 3 of the following 5 domains: patient's assessment of disease activity, physician's assessment of disease activity, patient's

Outcome measures

Outcome measures
Measure	Group 1 - Secukinumab (150 mg + 300 mg) n=83 Participants In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Group 2 - Placebo/Secukinumab n=83 Participants In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label 150 or 300 mg secukinumab every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients
Proportion of Participants With American College of Rheumatology (ACR)-20 Response	56 Participants	26 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Full Analysis Set (FAS)

ACR 50 responder has ≥ 50% improvement in TJC and SJC and \>25% improvement in 3 of the following 5 domains: patient's assessment of disease activity, physician's assessment of disease activity, patient's assessment of PsA pain, HAQ-DI, or hsCRP.

Outcome measures

Outcome measures
Measure	Group 1 - Secukinumab (150 mg + 300 mg) n=83 Participants In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Group 2 - Placebo/Secukinumab n=83 Participants In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label 150 or 300 mg secukinumab every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients
Proportion of Participants With American College of Rheumatology (ACR)-50 Response	38 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Full Analysis Set (FAS)

Repeated measures mixed effect (MMRM) analysis of SPARCC total score change from baseline to Week 12 between the 2 treatment groups. SPARCC index ranges from 0 to 16.

Outcome measures

Outcome measures
Measure	Group 1 - Secukinumab (150 mg + 300 mg) n=83 Participants In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Group 2 - Placebo/Secukinumab n=81 Participants In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label 150 or 300 mg secukinumab every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients
Spondyloarthritis Research Consortium of Canada (SPARCC)	-2.23 Adjusted mean change in scores Standard Error 0.29	-1.57 Adjusted mean change in scores Standard Error 0.29

Adverse Events

Treatment Group 1 - Secukinumab (150+300 mg)

Serious events: 9 serious events

Other events: 79 other events

Deaths: 1 deaths

Treatnent Group 2 - Placebo/Secukinumab

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Group 1 - Secukinumab (150+300 mg) n=161 participants at risk In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Treatnent Group 2 - Placebo/Secukinumab n=83 participants at risk In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label 150 or 300 mg secukinumab every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients
Cardiac disorders Acute myocardial infarction	1.2% 2/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Cardiac disorders Atrial fibrillation	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Cardiac disorders Coronary artery stenosis	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Gastrointestinal disorders Diarrhoea	0.00% 0/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	1.2% 1/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations COVID-19	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Injury, poisoning and procedural complications Femur fracture	0.00% 0/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	1.2% 1/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Injury, poisoning and procedural complications Incisional hernia	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Metabolism and nutrition disorders Malnutrition	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Reproductive system and breast disorders Ovarian cyst	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Reproductive system and breast disorders Uterine polyp	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 (862) 778-8300

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. 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 or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER

Measure	Treatment Group 1 - Secukinumab (150+300 mg) n=161 participants at risk In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 (although primary outcome was to week 12 only) In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52	Treatnent Group 2 - Placebo/Secukinumab n=83 participants at risk In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label 150 or 300 mg secukinumab every 4 weeks from Week 12, as follows, based on their severity of skin disease at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients
Eye disorders Dry eye	1.9% 3/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	3.6% 3/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Gastrointestinal disorders Abdominal pain	3.1% 5/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	3.6% 3/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Gastrointestinal disorders Constipation	2.5% 4/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	1.2% 1/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Gastrointestinal disorders Diarrhoea	4.3% 7/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	7.2% 6/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Gastrointestinal disorders Nausea	2.5% 4/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	1.2% 1/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
General disorders Asthenia	2.5% 4/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	1.2% 1/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
General disorders Fatigue	2.5% 4/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations Bronchitis	5.0% 8/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	2.4% 2/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations Gastroenteritis	2.5% 4/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	1.2% 1/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations Influenza	4.3% 7/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	3.6% 3/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations Nasopharyngitis	11.8% 19/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	4.8% 4/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations Oral herpes	2.5% 4/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	1.2% 1/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations Pharyngitis	3.1% 5/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	0.00% 0/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations Upper respiratory tract infection	2.5% 4/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	2.4% 2/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Infections and infestations Urinary tract infection	6.2% 10/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	3.6% 3/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Injury, poisoning and procedural complications Fall	0.62% 1/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	2.4% 2/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 3/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	3.6% 3/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Musculoskeletal and connective tissue disorders Back pain	2.5% 4/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	2.4% 2/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Nervous system disorders Dizziness	1.2% 2/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	2.4% 2/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Nervous system disorders Headache	8.1% 13/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	3.6% 3/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Respiratory, thoracic and mediastinal disorders Cough	5.6% 9/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	2.4% 2/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	2.4% 2/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.2% 2/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	2.4% 2/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Vascular disorders Hypertension	5.6% 9/161 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period	1.2% 1/83 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for 12 weeks. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period