Trial Outcomes & Findings for Study of Safety, Tolerability, and Efficacy of Secukinumab in Subjects With Moderate to Severe Palmoplantar Psoriasis (NCT NCT01806597)

Last Updated: 2018-02-22

Results Overview

palmoplantar Investigator's Global Assessment (ppIGA) response after 16 weeks of treatment. To be considered a ppIGA responder at Week 16, a subject must have ppIGA of 0 or 1 at Week 16 and a reduction of at least 2 points on the ppIGA scale from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

205 participants

Primary outcome timeframe

Week 16

Results posted on

2018-02-22

Participant Flow

Week 16 was considered the first dose of Treatment Period 2. Week 132 visit was the final visit of Treatment Period 2, and no study treatment was administered at this visit.

Patients who completed Period 2 \& patients who prematurely discontinued treatment or withdrew from study entered the treatment-free Follow-up (FU) Period (no study treatment was administered during Period) included only 1 visit at Week 140 (End of FU), which was 8 weeks after the end of Period 2 \& 12 weeks after the last dose of study drug.

Participant milestones

Participant milestones
Measure	AIN457 150mg AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo - AIN457 150 mg all placebo patients who were re-randomized to secukinumab 150 mg at re-randomization	Placebo - AIN457 300mg all placebo patients who were re-randomized to AIN457 300 mg at re-randomization	Placebo placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.	Any AIN457 Dose All patients who were injected with AIN457
Period 1 (Baseline to Week 16) STARTED	68	69	0	0	68	0
Period 1 (Baseline to Week 16) COMPLETED	63	64	0	0	63	0
Period 1 (Baseline to Week 16) NOT COMPLETED	5	5	0	0	5	0
Treatment Period 2 (Week 16 to Week 132) STARTED	63	64	31	31	1	0
Treatment Period 2 (Week 16 to Week 132) COMPLETED	24	44	17	20	0	0
Treatment Period 2 (Week 16 to Week 132) NOT COMPLETED	39	20	14	11	1	0
Follow-up Period (Week 132 to Week 140) STARTED	0	0	0	0	3	161
Follow-up Period (Week 132 to Week 140) COMPLETED	0	0	0	0	3	149
Follow-up Period (Week 132 to Week 140) NOT COMPLETED	0	0	0	0	0	12

Reasons for withdrawal

Reasons for withdrawal
Measure	AIN457 150mg AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo - AIN457 150 mg all placebo patients who were re-randomized to secukinumab 150 mg at re-randomization	Placebo - AIN457 300mg all placebo patients who were re-randomized to AIN457 300 mg at re-randomization	Placebo placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.	Any AIN457 Dose All patients who were injected with AIN457
Period 1 (Baseline to Week 16) Adverse Event	1	1	0	0	2	0
Period 1 (Baseline to Week 16) Lack of Efficacy	1	0	0	0	1	0
Period 1 (Baseline to Week 16) Protocol Violation	0	1	0	0	0	0
Period 1 (Baseline to Week 16) Withdrawal by Subject	3	2	0	0	2	0
Period 1 (Baseline to Week 16) Physician Decision	0	1	0	0	0	0
Treatment Period 2 (Week 16 to Week 132) Adverse Event	9	6	4	3	1	0
Treatment Period 2 (Week 16 to Week 132) Lack of Efficacy	12	5	3	1	0	0
Treatment Period 2 (Week 16 to Week 132) Lost to Follow-up	2	0	0	0	0	0
Treatment Period 2 (Week 16 to Week 132) Physician Decision	1	1	0	0	0	0
Treatment Period 2 (Week 16 to Week 132) Protocol Violation	2	0	0	0	0	0
Treatment Period 2 (Week 16 to Week 132) study terminated by sponsor	0	1	0	1	0	0
Treatment Period 2 (Week 16 to Week 132) Withdrawal by Subject	10	5	6	5	0	0
Treatment Period 2 (Week 16 to Week 132) non-compliance with study treatment	2	2	1	1	0	0
Treatment Period 2 (Week 16 to Week 132) Death	1	0	0	0	0	0
Follow-up Period (Week 132 to Week 140) Withdrawal by Subject	0	0	0	0	0	5
Follow-up Period (Week 132 to Week 140) Adverse Event	0	0	0	0	0	2
Follow-up Period (Week 132 to Week 140) Lack of Efficacy	0	0	0	0	0	2
Follow-up Period (Week 132 to Week 140) Lost to Follow-up	0	0	0	0	0	2
Follow-up Period (Week 132 to Week 140) Physician Decision	0	0	0	0	0	1

Baseline Characteristics

Study of Safety, Tolerability, and Efficacy of Secukinumab in Subjects With Moderate to Severe Palmoplantar Psoriasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AIN457 150mg n=68 Participants AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg n=69 Participants AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=68 Participants placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.	Total n=205 Participants Total of all reporting groups
Age, Continuous	52.4 years STANDARD_DEVIATION 12.56 • n=5 Participants	48.8 years STANDARD_DEVIATION 14.21 • n=7 Participants	50.9 years STANDARD_DEVIATION 12.95 • n=5 Participants	50.7 years STANDARD_DEVIATION 13.28 • n=4 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	31 Participants n=7 Participants	34 Participants n=5 Participants	93 Participants n=4 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	38 Participants n=7 Participants	34 Participants n=5 Participants	112 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 16

Population: Full Analysis Set (FAS): The FAS comprised of all patients from the randomized set to who study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned to at randomization.

Outcome measures

Outcome measures
Measure	Placebo - AIN457 300 mg all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 150mg n=68 Participants AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg n=69 Participants AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=68 Participants placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Percentages of Participants With Palmoplantar Investigator Global Assessmnet (ppIGA) 0 or 1 Response After 16 Weeks of Treatment	—	—	22 Percentages of participants	33.3 Percentages of participants	1.5 Percentages of participants

SECONDARY outcome

Timeframe: Week 1, week 2, week 4, week, 8, week 12, week 16

Population: FAS

ppIGA: Palmoplantar Ivestigator's Global Assessment. The IGA mod 2011 rating scale: The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Based on this scale, a patient was considered as an IGA 0 or 1 responder if they achieved a score of 0 or 1 and improved by at least 2 points on the IGA scale at a given time point compared to their score at randomization (baseline).

Outcome measures

Outcome measures
Measure	Placebo - AIN457 300 mg all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 150mg n=68 Participants AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg n=69 Participants AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=68 Participants placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Percentages of Participants With Palmoplantar Investigator Global Assessment (ppIGA) 0 or 1 Response - Treatment Period I Week 1	—	—	1.5 Percentages of participants	1.4 Percentages of participants	0 Percentages of participants
Percentages of Participants With Palmoplantar Investigator Global Assessment (ppIGA) 0 or 1 Response - Treatment Period I Week 2	—	—	1.5 Percentages of participants	7.2 Percentages of participants	0 Percentages of participants
Percentages of Participants With Palmoplantar Investigator Global Assessment (ppIGA) 0 or 1 Response - Treatment Period I Week 4	—	—	4.4 Percentages of participants	8.7 Percentages of participants	0 Percentages of participants
Percentages of Participants With Palmoplantar Investigator Global Assessment (ppIGA) 0 or 1 Response - Treatment Period I Week 8	—	—	17.6 Percentages of participants	26.1 Percentages of participants	0 Percentages of participants
Percentages of Participants With Palmoplantar Investigator Global Assessment (ppIGA) 0 or 1 Response - Treatment Period I Week 12	—	—	20.6 Percentages of participants	33.3 Percentages of participants	1.5 Percentages of participants
Percentages of Participants With Palmoplantar Investigator Global Assessment (ppIGA) 0 or 1 Response - Treatment Period I Week 16	—	—	22.1 Percentages of participants	33.3 Percentages of participants	1.5 Percentages of participants

SECONDARY outcome

Timeframe: Week 16, Week 20, Week 28, Week 32, Week 64, Week 132

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo - AIN457 300 mg n=31 Participants all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo n=1 Participants Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 150mg n=68 Participants AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg n=69 Participants AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=31 Participants placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Treatment Period II Week 16	0.0 Percentages of participants 7.983	100.0 Percentages of participants 4.479	22.1 Percentages of participants 15.624	33.3 Percentages of participants 12.074	0.0 Percentages of participants 8.880
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Treatment Period II Week 20	9.7 Percentages of participants 12.625	0.0 Percentages of participants NA	32.4 Percentages of participants 14.307	33.3 Percentages of participants 13.104	12.9 Percentages of participants 11.570
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Treatment Period II Week 28	51.6 Percentages of participants 10.441	100.0 Percentages of participants NA	29.4 Percentages of participants 15.232	44.9 Percentages of participants 14.258	32.3 Percentages of participants 14.560
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Treatment Period II Week 32	41.9 Percentages of participants 5.844	0.0 Percentages of participants NA	29.4 Percentages of participants 14.658	42.0 Percentages of participants 11.688	35.5 Percentages of participants 11.728
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Treatment Period II Week 64	48.4 Percentages of participants	0.0 Percentages of participants	26.5 Percentages of participants	46.4 Percentages of participants	29.0 Percentages of participants
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Treatment Period II Week 132	35.5 Percentages of participants	0.0 Percentages of participants	22.1 Percentages of participants	27.5 Percentages of participants	12.9 Percentages of participants

SECONDARY outcome

Timeframe: Week 16, Week 24, Week 28, Week 80

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo - AIN457 300 mg n=31 Participants all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo n=6 Participants Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 150mg n=68 Participants AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg n=69 Participants AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=31 Participants placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Entire Treatment Period Week 16	0.0 Percentages of participants	25.0 Percentages of participants	23.4 Percentages of participants	37.7 Percentages of participants	0.0 Percentages of participants
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Entire Treatment Period Week 24	36.7 Percentages of participants	100.0 Percentages of participants	40.7 Percentages of participants	44.1 Percentages of participants	20.0 Percentages of participants
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Entire Treatment Period Week 28	48.3 Percentages of participants	0.0 Percentages of participants	34.5 Percentages of participants	50.8 Percentages of participants	20.0 Percentages of participants
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Entire Treatment Period Week 80	68.2 Percentages of participants	—	41.7 Percentages of participants	65.3 Percentages of participants	45.0 Percentages of participants

SECONDARY outcome

Timeframe: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16

Population: FAS

Psoriasis Area and Severity Index (PASI) is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease).

Outcome measures

Outcome measures
Measure	Placebo - AIN457 300 mg all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 150mg n=68 Participants AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg n=69 Participants AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=68 Participants placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score -Treatment Period I Week 1	—	—	-1.13 Units on a scale Standard Deviation 4.797	-2.22 Units on a scale Standard Deviation 4.334	-0.85 Units on a scale Standard Deviation 3.355
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score -Treatment Period I Week 2	—	—	-3.11 Units on a scale Standard Deviation 7.669	-5.32 Units on a scale Standard Deviation 6.120	-1.90 Units on a scale Standard Deviation 5.434
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score -Treatment Period I Week 4	—	—	-6.69 Units on a scale Standard Deviation 9.890	-9.18 Units on a scale Standard Deviation 9.734	-3.95 Units on a scale Standard Deviation 7.424
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score -Treatment Period I Week 8	—	—	-9.74 Units on a scale Standard Deviation 12.779	-11.30 Units on a scale Standard Deviation 11.954	-3.22 Units on a scale Standard Deviation 8.316
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score -Treatment Period I Week 12	—	—	-10.15 Units on a scale Standard Deviation 14.409	-12.83 Units on a scale Standard Deviation 12.286	-3.07 Units on a scale Standard Deviation 8.479
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score -Treatment Period I Week 16	—	—	-9.41 Units on a scale Standard Deviation 15.984	-13.35 Units on a scale Standard Deviation 12.941	-2.43 Units on a scale Standard Deviation 8.527

SECONDARY outcome

Timeframe: Week 16, Week 32, Week 80, Week 132

Population: FAS

Psoriasis Area and Severity Index (PASI) is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease).

Outcome measures

Outcome measures
Measure	Placebo - AIN457 300 mg n=31 Participants all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo n=6 Participants Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 150mg n=68 Participants AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg n=69 Participants AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=31 Participants placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score (Observed Cases) - Entire Treatment Set Week 16	-3.11 Units on a scale Standard Deviation 7.983	-7.15 Units on a scale Standard Deviation 4.479	-8.97 Units on a scale Standard Deviation 15.624	-12.67 Units on a scale Standard Deviation 12.074	-1.57 Units on a scale Standard Deviation 8.880
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score (Observed Cases) - Entire Treatment Set Week 32	-15.09 Units on a scale Standard Deviation 12.625	-11.40 Units on a scale	-16.29 Units on a scale Standard Deviation 14.307	-17.43 Units on a scale Standard Deviation 13.104	-15.49 Units on a scale Standard Deviation 11.570
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score (Observed Cases) - Entire Treatment Set Week 132	-13.82 Units on a scale Standard Deviation 5.844	—	-16.74 Units on a scale Standard Deviation 14.658	-19.16 Units on a scale Standard Deviation 11.688	-17.07 Units on a scale Standard Deviation 11.728
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score (Observed Cases) - Entire Treatment Set Week 80	-16.70 Units on a scale Standard Deviation 10.441	—	-18.05 Units on a scale Standard Deviation 15.232	-19.27 Units on a scale Standard Deviation 14.258	-13.71 Units on a scale Standard Deviation 14.560

SECONDARY outcome

Timeframe: Over time up to week 132

Population: FAS

To investigate the development of immunogenicity against secukinumab

Outcome measures

Outcome measures
Measure	Placebo - AIN457 300 mg n=31 Participants all placebo patients who were re-randomized to secukinumab 300 mg at re-randomization.	Placebo Placebo AIN457 (2sc injections) once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 150mg n=68 Participants AIN457 150mg sub-cutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	AIN457 300 mg n=69 Participants AIN457 300 mg (2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=31 Participants placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.
Number of Participants Developing Anti-secukinumab Antibodies	3 Participants	—	2 Participants	2 Participants	2 Participants

Adverse Events

Any AIN457 150 mg

Serious events: 19 serious events

Other events: 75 other events

Deaths: 0 deaths

Any AIN457 300 mg

Serious events: 13 serious events

Other events: 68 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Any AIN457 Dose

Serious events: 32 serious events

Other events: 143 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 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 (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Any AIN457 150 mg n=99 participants at risk AIN457 150mg subcutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	Any AIN457 300 mg n=100 participants at risk AIN457 300mg subcutaneous ((2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=68 participants at risk placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.	Any AIN457 Dose n=199 participants at risk All patients who were injected with AIN457
Cardiac disorders Angina pectoris	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Cardiac disorders Coronary artery occlusion	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Dyspepsia	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Asthenia	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Non-cardiac chest pain	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Hepatobiliary disorders Hepatitis	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Cellulitis of male external genital organ	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Diverticulitis	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Gastroenteritis	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Infective keratitis	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Pyelonephritis	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Sepsis	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Skin infection	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Injury, poisoning and procedural complications Fibula fracture	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Injury, poisoning and procedural complications Fracture displacement	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Injury, poisoning and procedural complications Humerus fracture	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Injury, poisoning and procedural complications Peripheral nerve injury	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Injury, poisoning and procedural complications Tendon injury	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Metabolism and nutrition disorders Dehydration	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Metabolism and nutrition disorders Electrolyte imbalance	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Metabolism and nutrition disorders Hypokalaemia	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders Tenosynovitis stenosans	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Nervous system disorders Cerebrovascular accident	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Nervous system disorders Hypoaesthesia	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Nervous system disorders Lumbar radiculopathy	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Nervous system disorders Paraesthesia	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Nervous system disorders Polyneuropathy	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Nervous system disorders Transient global amnesia	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Psychiatric disorders Completed suicide	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.50% 1/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.

Other adverse events
Measure	Any AIN457 150 mg n=99 participants at risk AIN457 150mg subcutaneous (s.c.) injection plus a placebo AIN457 s.c. injection once weekly for 5 weeks followed by dosing every 4 weeks	Any AIN457 300 mg n=100 participants at risk AIN457 300mg subcutaneous ((2 s.c. injections of the 150 mg dose) once weekly for 5 weeks followed by dosing every 4 weeks	Placebo n=68 participants at risk placebo AIN457 (2 sc injections) once weekly for 5 weeks, followed by dosing every 4 weeks.	Any AIN457 Dose n=199 participants at risk All patients who were injected with AIN457
Musculoskeletal and connective tissue disorders Back pain	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	10.0% 10/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.9% 2/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	6.0% 12/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders Muscle spasms	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 2/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Eye disorders Blepharitis	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Abdominal pain	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 2/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Constipation	3.0% 3/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 3/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Dental caries	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Diarrhoea	4.0% 4/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	4.0% 4/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	4.0% 8/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.0% 3/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	3.0% 3/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	3.0% 6/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Nausea	3.0% 3/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Gastrointestinal disorders Toothache	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 2/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Chills	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Fatigue	4.0% 4/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.5% 5/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Influenza like illness	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	3.0% 3/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Injection site haematoma	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 3/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Injection site reaction	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Oedema peripheral	5.1% 5/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	4.0% 4/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	4.5% 9/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Peripheral swelling	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
General disorders Pyrexia	4.0% 4/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.5% 5/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Hepatobiliary disorders Hepatic steatosis	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 3/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Bronchitis	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 2/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Cellulitis	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 2/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Conjunctivitis	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	3.0% 3/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.5% 5/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Folliculitis	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Gastroenteritis	5.1% 5/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	4.0% 4/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	4.5% 9/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Genital infection fungal	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Impetigo	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Influenza	4.0% 4/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	7.0% 7/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	5.9% 4/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	5.5% 11/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Localised infection	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	3.0% 3/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 3/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Nasopharyngitis	14.1% 14/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	8.0% 8/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	5.9% 4/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	11.1% 22/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Oral candidiasis	0.00% 0/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	5.0% 5/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.5% 5/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Oral herpes	3.0% 3/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 2/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.5% 5/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Pharyngitis	3.0% 3/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	6.0% 6/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	4.5% 9/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Rhinitis	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 2/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Sinusitis	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	3.0% 3/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Skin infection	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 2/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.5% 1/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Tinea pedis	5.1% 5/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 1/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	3.0% 6/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Tonsillitis	1.0% 1/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	3.0% 3/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	2.0% 4/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Tooth abscess	2.0% 2/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	1.0% 2/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Upper respiratory tract infection	10.1% 10/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	20.0% 20/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	4.4% 3/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	15.1% 30/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.
Infections and infestations Urinary tract infection	3.0% 3/99 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	7.0% 7/100 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	0.00% 0/68 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.	5.0% 10/199 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First treatment until Last Patient Last Visit.