OASIS-1: A Study to Evaluate the Efficacy and Safety of Mirikizumab (LY3074828) in Participants With Moderate-to-Severe Plaque Psoriasis

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03482011
• Collaborator: (none)
• Enrollment: 530
• Locations: 69
• Arms: 2
• Actual Duration (Months): 20.8
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of mirikizumab in participants with moderate to severe plaque psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Mirikizumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 530 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Withdrawal Maintenance Dosing Period to Evaluate the Efficacy and Safety of Mirikizumab in Patients With Moderate-to-Severe Plaque Psoriasis OASIS-1
• Actual Study Start Date: Apr 24, 2018
• Actual Primary Completion Date: Mar 21, 2019
• Actual Study Completion Date: Jan 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mirikizumab Induction Period: Participants received 250 milligrams (mg) mirikizumab administered subcutaneously (SC) every 4 weeks (Q4W). Maintenance Period: Participants received one of the four options below: Placebo administered SC every 8 weeks (Q8W) for responders (≥PASI 90). 125 mg mirikizumab administered SC Q8W for responders (≥PASI 90). 250 mg mirikizumab administered SC Q8W for responders (≥PASI 90). 250 mg mirikizumab administered SC Q8W for non-responders (<PASI 90).	Drug: Mirikizumab; Administered SC; Other Names: LY3074828
Placebo Comparator: Placebo Induction Period: Participants received placebo administered SC Q4W. Maintenance Period: Participants received one of the two options below: Placebo administered SC Q8W for responders (≥PASI 90). 250 mg mirikizumab administered SC Q4W during week 16 to week 32 and Q8W during week 40 and 48 for non-responders (< PASI 90).	Drug: Placebo; Administered SC

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Static Physician's Global Assessment of (sPGA) (0,1) With at Least a 2-point Improvement From Baseline [Week 16]

   The sPGA is the physician's determination of the participant's psoriasis (PsO) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's PsO was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline.

2. Percentage of Participants Achieving a ≥90% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 90) [Week 16]

   PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).

Secondary Outcome Measures

1. Percentage of Participants Achieving a ≥75% Improvement From Baseline in PASI (PASI 75) [Week 4]

   PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).

2. Percentage of Participants Achieving a ≥75% Improvement From Baseline in PASI (PASI 75) [Week 16]

   PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).

3. Percentage of Participants Achieving a ≥100% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 100) [Week 16]

   PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).

4. Percentage of Participants With ≤1% of Body Surface Area (BSA) With Psoriasis Involvement [Week 16]

   The BSA is the percentage involvement of psoriasis on each participant's body surface on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand (including the palm, fingers, and thumb). The total BSA affected was the summation of individual regions affected. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.

5. Percentage of Participants With a Psoriasis Symptoms Scale (PSS) Symptoms Score of 0 in Those With a PSS Symptoms Score ≥1 at Baseline [Week 16]

   PSS is a patient-administered assessment of 4 symptoms (itch, pain, stinging, and burning); 3 signs (redness, scaling, and cracking); and 1 item on the discomfort related to symptoms/signs. The overall severity for each individual symptom/sign from the patient's psoriasis is indicated by selecting the number from a numeric rating scale (NRS) of 0 to 10 that best describes the worst level of each symptom/sign in the past 24 hours, where 0=no symptom/sign and 10=worst imaginable symptom/sign. In addition, a symptoms score ranging from 0 (no symptoms) to 40 (worst imaginable symptoms), and a signs score of 0 (no signs) to 30 (worst imaginable signs) will be reported. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.

6. Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) Total Score of (0,1) With at Least a 5-Point Improvement (Reduction) From Baseline in Participants With a Baseline DLQI Total Score ≥5 [Week 16]

   The DLQI is a patient-reported, 10-question, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). A DLQI total score of 0 to 1 is considered as having no effect on a patient's health-related quality of life (HRQoL), and a 5-point change from baseline is considered as the minimal clinically important difference (MCID) threshold. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.

7. Percentage of Participants Maintaining Clinical Response (PASI 90) After Re-randomization at the Start of the Randomized Withdrawal Period [Week 52]

   PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).

8. Change in Palmoplantar Psoriasis Severity Index (PPASI) Total Score in Participants With Palmoplantar Involvement at Baseline [Week 16]

   The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. Least Squares Mean (LS Mean) was calculated using mixed model repeated measures (MMRM) model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as covariates.

9. Change in Psoriasis Scalp Severity Index (PSSI) Total Score in Participants With Scalp Involvement at Baseline [Week 16]

   The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity). LS Mean was calculated using MMRM model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as covariates.

10. Change in Nail Psoriasis Severity Index (NAPSI) Total Score in Participants With Fingernail Involvement at Baseline [Week 16]

    The NAPSI scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix PsO by area of involvement. The fingernail is divided into quadrants. Each fingernail is given a score for fingernail bed PsO 0 (none) to 4 (PsO in 4 quadrants of the fingernail) and fingernail matrix PsO 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix PsO in each quadrant. The sum of all fingernails equals the total NAPSI score range is from 0 (no effect) to 80 (more severe psoriasis). LS Mean was calculated using MMRM model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as covariates.

11. Change From Baseline on the Short Form (SF)-36 Physical Component Summary (PCS) [Baseline, Week 16]

    SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as fixed factors.

12. Change From Baseline on the SF-36 Mental Component Summary (MCS) [Baseline, Week 16]

    SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as fixed factors.

13. Percentage of Participants With Patient's Global Assessment of Psoriasis (PatGA (0,1)) and >=2 Improvement From Baseline [Baseline, Week 16]

    The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.

14. Change From Baseline on the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI-PSO) [Baseline, Week 16]

    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism and impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100) with higher numbers indicating greater impairment and less productivity, that is, worse outcomes. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as fixed factors.

15. Change From Baseline in Quick Inventory of Depressive Symptomology (QIDS-SR16) Total Score in Those With a Baseline QIDS-SR16 Total Score ≥11 [Baseline, Week 16]

    QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. Whereas 0-5 indicates no symptoms. LS Mean was calculated using ANCOVA model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as fixed factors.

16. Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) (0,1) [Week 16]

    The DLQI is a patient-reported, 10-question, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). A DLQI total score of 0 to 1 is considered as having no effect on a patient's health-related quality of life (HRQoL), and a 5-point change from baseline is considered as the minimal clinically important difference (MCID) threshold. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.

17. Induction Period: Pharmacokinetics (PK): Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Mirikizumab at Week 16 [Week 16: Day 113]

    Minimum observed serum concentration at steady state (Ctrough,ss) of mirikizumab at Week 16.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Present with chronic plaque psoriasis based on an investigator confirmed diagnosis of chronic psoriasis vulgaris for at least 6 months prior to baseline and meet the following criteria:

• plaque psoriasis involving ≥10% BSA and absolute PASI score ≥12 in affected skin at screening and baseline

• sPGA score of ≥3 at screening and baseline

• Candidate for systemic therapy and/or phototherapy for psoriasis.

Exclusion Criteria:

• Have an unstable or uncontrolled illness, including but not limited to a cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurologic disease or abnormal laboratory values at screening, that in the opinion of the investigator, would potentially affect participant safety within the study or of interfering with the interpretation of data.

• Breastfeeding or nursing women.

• Have had serious, opportunistic, or chronic/recurring infection within 3 months prior to screening.

• Have received a Bacillus Calmette-Guerin (BCG) vaccination within 12 months or received live vaccine(s) (including attenuated live vaccines) within 12 weeks of baseline or intend to receive either during the study.

• Have any other skin conditions (excluding psoriasis) that would affect interpretation of the results.

• Have received systemic nonbiologic psoriasis therapy or phototherapy within 28 days prior to baseline.

• Have received topical psoriasis treatment within 14 days prior to baseline.

• Have received anti-tumor necrosis factor (TNF) biologics, or anti-interleukin (IL)-17 targeting biologics within 12 weeks prior to baseline.

• Have previous exposure to any biologic therapy targeting IL-23 (including ustekinumab), either licensed or investigational.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Connecticut	Farmington	Connecticut	United States	06032
2	Florida Academic Dermatology Centers	Coral Gables	Florida	United States	33134
3	Renstar Medical Research	Ocala	Florida	United States	34470
4	Forward Clinical Trials, Inc	Tampa	Florida	United States	33624
5	Arlington Dermatology	Rolling Meadows	Illinois	United States	60008
6	The South Bend Clinic	South Bend	Indiana	United States	46617
7	Oregon Medical Research Center	Portland	Oregon	United States	97223
8	Dermatology and Skin Surgery Center	Exton	Pennsylvania	United States	19341
9	University of Utah MidValley Dematology	Murray	Utah	United States	84107
10	Multicare Health System	Tacoma	Washington	United States	98405
11	Gemeinschaftspraxis Mahlow	Mahlow	Brandenburg	Germany	15831
12	Universitätsklinikum Münster	Münster	Nordrhein-Westfalen	Germany	48149
13	Praxis Gerlach	Dresden	Sachsen	Germany	01097
14	Charité Universitätsmedizin Berlin	Berlin		Germany	10117
15	ISA GmbH	Berlin		Germany	10789
16	Universitätsklinikum Hamburg - Eppendorf	Hamburg		Germany	20246
17	Clinical Research Hamburg GmbH	Hamburg		Germany	22143
18	Toho University School of Medicine, Sakura Hospital	Sakura	Chiba	Japan	285-8741
19	Takagi Dermatological Clinic	Obihiro	Hokkaido	Japan	080-0013
20	Kanto Rosai Hospital	Kawasaki	Kanagawa	Japan	211-8510
21	Yokohama City University Hospital	Yokohama	Kanagawa	Japan	236-0004
22	Ryukyu University Hospital	Nakagami-gun	Okinawa	Japan	903-0215
23	Kume Clinic	Nishi-ku Sakai-shi	Osaka	Japan	593-8324
24	Shimane University Hospital	Izumo	Shimane	Japan	693-8501
25	Tokyo Medical University Hachioji Medical Center	Hachioji	Tokyo	Japan	193-0998
26	NTT Medical Center Tokyo	Shinagawa-KU	Tokyo	Japan	141-8625
27	Tokyo Medical University Hospital	Shinjuku-ku	Tokyo	Japan	160-0023
28	Seibo Hospital	Shinjuku-ku	Tokyo	Japan	161-8521
29	Shirasaki Clinic	Takaoka-shi	Toyama	Japan	9330871
30	Bucheon St. Mary's Hospital	Bucheon,	Gyeonggi-do	Korea, Republic of	14647
31	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
32	Bundang CHA General Hospital	Sungnam-si	Gyeonggi-do	Korea, Republic of	13496
33	Ajou University Hospital	Suwon	Gyeonggi-do	Korea, Republic of	16499
34	Kyung Hee University Hospital	Seoul	Korea	Korea, Republic of	02447
35	Korea University Guro Hospital	Seoul	Korea	Korea, Republic of	08308
36	Ulsan University Hospital	Ulsan	Korea	Korea, Republic of	44033
37	Chungnam National University Hospital	Daejeon		Korea, Republic of	35015
38	Chonnam National University Hospital	Gwangju		Korea, Republic of	61469
39	Severance Hospital Yonsei University Health System	Seoul		Korea, Republic of	03722
40	Hanyang University Medical Center	Seoul		Korea, Republic of	04763
41	Konkuk University Hospital	Seoul		Korea, Republic of	05030
42	Centro Medico del Angel S.C.	Mexicali	Baja California	Mexico	21100
43	Hospital de Jesus	Mexico City	Distrito Federal	Mexico	06090
44	Instituto Dermatologico de Jalisco Dr. Jose Barba Rubio	Zapopan	Jalisco	Mexico	45190
45	Clínica Enfermedades Crónicas y Procedimientos Especiales SC	Morella	Michoacan	Mexico	58249
46	B&B Investigaciones Medicas, SC	Mazatlan	Sinaloa	Mexico	82140
47	Kohler Milstein Research, S.A. de C.V.	Merida	Yucatan	Mexico	97070
48	RM Pharma Specialists S.A. de C.V.	Distrito Federal		Mexico	3100
49	Instituto de Investigaciones Aplicadas a la Neurociencia A.C	Durango		Mexico	34000
50	NZOZ ZDROWIE Osteo-Medic	Bialystok		Poland	15-351
51	"Dermed" Centrum Medyczne Sp. z o.o.	Lodz		Poland	90-265
52	Lubelskie Centrum Diagnostyczne	Swidnik		Poland	21-040
53	Centrum Medyczne AMED	Warszawa		Poland	01-518
54	DermMEDICA Sp. z o.o.	Wroclaw		Poland	51-318
55	Office of Dr. Alma M. Cruz	Carolina		Puerto Rico	00985
56	GCM Medical Group PSC	San Juan		Puerto Rico	00909
57	GBUZ Clinical dermatology and venereological dispensary	Krasnodar		Russian Federation	350000
58	State scientific centre for dermatovenerology and cosmetolog	Moscow		Russian Federation	107076
59	First Moscow State Medical University n.a. Sechenov	Moscow		Russian Federation	119991
60	GOU VPO 'Smolensk State Medical Academy of Ministry of Health and Social Development of Russian Federation'	Smolensk		Russian Federation	214000
61	SPb SBHI Skin-venerologic dispensary #10	St. Petersburg		Russian Federation	194021
62	Tver State Medical University	Tver		Russian Federation	170100
63	National Taiwan University Hospital	Taipei City	Zhongzheng District	Taiwan	100
64	National Taiwan University Hospital Hsin-Chu	Hsinchu		Taiwan	30059
65	Chang Gung Memorial Hospital - Kaohsiung	Kaohsiung		Taiwan	83301
66	Taipei Medical University- Shuang Ho Hospital	New Taipei City		Taiwan	23561
67	Chung Shan Medical University Hospital	Taichung City		Taiwan	40201
68	National Cheng Kung University Hospital	Tainan		Taiwan	70403
69	Chang Gung Memorial Hospital - Linkou	Taoyuan Hsien		Taiwan	10508

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Dec 12, 2018
• Statistical Analysis Plan - Mar 28, 2019

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03482011
• Other Study ID Numbers: 16505; I6T-MC-AMAK; 2017-003298-32
• First Posted: Mar 29, 2018
• Last Update Posted: Sep 25, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: Psoriasis; IL-23
• Additional relevant MeSH terms: Psoriasis; Mirikizumab

Study Results

Participant Flow

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W	Placebo Q4W to Placebo Q8W (Placebo Responder)	Placebo Q4W to 250 mg Miri Q4W /Q8W (Placebo Non-Responders)	250 mg Miri Q4W Responders to Placebo Q8W	250 mg Miri Q4W Responders to 125 mg Miri Q8W	250 mg Miri Q4W Responder to 250 mg Miri Q8W	250 mg Miri Q4W to 250 mg Miri Q8W (Miri Non-Responders)
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 milligrams (mg) mirikizumab (miri) administered SC Q4W.	Maintenance Period: Participants received placebo administered SC every 8 weeks (Q8W). Responders had ≥PASI 90. Participants had received placebo administered SC Q4W during induction period. Follow-up Period: Participants did not receive drug during the follow-up period.	Maintenance Period: Participants received 250 mg mirikizumab administered SC Q4W during week 16 to week 32 and Q8W during week 40 and 48. Non-responders had < PASI 90. Participants had received placebo administered SC Q4W during induction period. Follow-up Period: Participants did not receive drug during the follow-up period.	Maintenance Period: Participants received placebo administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period. Follow-up Period: Participants did not receive drug during the follow-up period.	Maintenance Period: Participants received 125 mg mirikizumab administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period. Follow-up Period: Participants did not receive drug during the follow-up period.	Maintenance Period: Participants received 250 mg mirikizumab administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period. Follow-up Period: Participants did not receive drug during the follow-up period.	Maintenance Period: Participants received 250 mg mirikizumab administered SC Q8W. Non-responders had < PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period. Follow-up Period: Participants did not receive drug during the follow-up period.
Period Title: Induction Period (16 Weeks)
STARTED	107	423	0	0	0	0	0	0
Received at Least One Dose of Study Drug	107	422	0	0	0	0	0	0
COMPLETED	101	412	0	0	0	0	0	0
NOT COMPLETED	6	11	0	0	0	0	0	0
Period Title: Induction Period (16 Weeks)
STARTED	0	0	7	94	91	90	91	140
Relapse	0	0	1	0	41	3	2	0
Roll Over to I6T-MC-AMAH (NCT03556202)	0	0	6	88	86	85	87	121
COMPLETED	0	0	6	90	86	86	87	123
NOT COMPLETED	0	0	1	4	5	4	4	17
Period Title: Induction Period (16 Weeks)
STARTED	0	0	1	10	2	4	4	21
COMPLETED	0	0	0	5	2	3	2	4
NOT COMPLETED	0	0	1	5	0	1	2	17

Baseline Characteristics

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W	Total
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.	Total of all reporting groups
Overall Participants	107	423	530
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (13.70)	46.4 (13.56)	46.3 (13.58)
Sex: Female, Male (Count of Participants)
Female	33 30.8%	124 29.3%	157 29.6%
Male	74 69.2%	299 70.7%	373 70.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 3.7%	13 3.1%	17 3.2%
Not Hispanic or Latino	11 10.3%	53 12.5%	64 12.1%
Unknown or Not Reported	92 86%	357 84.4%	449 84.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	14 13.1%	50 11.8%	64 12.1%
Asian	33 30.8%	139 32.9%	172 32.5%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.2%	1 0.2%
Black or African American	4 3.7%	2 0.5%	6 1.1%
White	56 52.3%	231 54.6%	287 54.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
South Korea	11 10.3%	45 10.6%	56 10.6%
Puerto Rico	5 4.7%	15 3.5%	20 3.8%
United States	16 15%	69 16.3%	85 16%
Japan	10 9.3%	44 10.4%	54 10.2%
Taiwan	12 11.2%	49 11.6%	61 11.5%
Poland	11 10.3%	44 10.4%	55 10.4%
Mexico	15 14%	61 14.4%	76 14.3%
Germany	16 15%	58 13.7%	74 14%
Russia	11 10.3%	38 9%	49 9.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Static Physician's Global Assessment of (sPGA) (0,1) With at Least a 2-point Improvement From Baseline
Description	The sPGA is the physician's determination of the participant's psoriasis (PsO) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's PsO was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	107	423
Number (95% Confidence Interval) [Percentage of participants]	6.5 6.1%	69.3 16.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	63.0
	Confidence Interval	(2-Sided) 95%; 56.5 to 69.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants Achieving a ≥90% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 90)
Description	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	107	423
Number (95% Confidence Interval) [Percentage of participants]	6.5 6.1%	64.3 15.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	57.8
	Confidence Interval	(2-Sided) 95%; 51.3 to 64.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Achieving a ≥75% Improvement From Baseline in PASI (PASI 75)
Description	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	107	423
Number (95% Confidence Interval) [Percentage of participants]	0.9 0.8%	17.0 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.6
	Confidence Interval	(2-Sided) 95%; 11.6 to 19.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants Achieving a ≥75% Improvement From Baseline in PASI (PASI 75)
Description	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	107	423
Number (95% Confidence Interval) [Percentage of participants]	9.3 8.7%	82.5 19.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	73.6
	Confidence Interval	(2-Sided) 95%; 67.1 to 80.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Achieving a ≥100% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 100)
Description	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	107	423
Number (95% Confidence Interval) [Percentage of participants]	0.9 0.8%	32.4 7.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	30.8
	Confidence Interval	(2-Sided) 95%; 26.0 to 35.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With ≤1% of Body Surface Area (BSA) With Psoriasis Involvement
Description	The BSA is the percentage involvement of psoriasis on each participant's body surface on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand (including the palm, fingers, and thumb). The total BSA affected was the summation of individual regions affected. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period:All randomized participants.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	107	423
Number (95% Confidence Interval) [Percentage of participants]	0.9 0.8%	49.2 11.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	48.1
	Confidence Interval	(2-Sided) 95%; 42.9 to 53.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With a Psoriasis Symptoms Scale (PSS) Symptoms Score of 0 in Those With a PSS Symptoms Score ≥1 at Baseline
Description	PSS is a patient-administered assessment of 4 symptoms (itch, pain, stinging, and burning); 3 signs (redness, scaling, and cracking); and 1 item on the discomfort related to symptoms/signs. The overall severity for each individual symptom/sign from the patient's psoriasis is indicated by selecting the number from a numeric rating scale (NRS) of 0 to 10 that best describes the worst level of each symptom/sign in the past 24 hours, where 0=no symptom/sign and 10=worst imaginable symptom/sign. In addition, a symptoms score ranging from 0 (no symptoms) to 40 (worst imaginable symptoms), and a signs score of 0 (no signs) to 30 (worst imaginable signs) will be reported. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had PSS symptoms score ≥1 at baseline.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	105	410
Number (95% Confidence Interval) [percentage of participants]	0 0%	19.0 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	18.3
	Confidence Interval	(2-Sided) 95%; 14.5 to 22.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) Total Score of (0,1) With at Least a 5-Point Improvement (Reduction) From Baseline in Participants With a Baseline DLQI Total Score ≥5
Description	The DLQI is a patient-reported, 10-question, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). A DLQI total score of 0 to 1 is considered as having no effect on a patient's health-related quality of life (HRQoL), and a 5-point change from baseline is considered as the minimal clinically important difference (MCID) threshold. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had a baseline DLQI Total Score ≥5

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	92	384
Number (95% Confidence Interval) [Percentage of participants]	5.4 5%	54.7 12.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	49.6
	Confidence Interval	(2-Sided) 95%; 42.8 to 56.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants Maintaining Clinical Response (PASI 90) After Re-randomization at the Start of the Randomized Withdrawal Period
Description	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Maintenance Period: All re-randomized participants who were responders (≥PASI 90).

Arm/Group Title	250 mg Miri Q4W Responders to Placebo Q8W	250 mg Miri Q4W Responders to 125 mg Miri Q8W	250 mg Miri Q4W Responder to 250 mg Miri Q8W
Arm/Group Description	Maintenance Period: Participants received placebo administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period.	Maintenance Period: Participants received 125 mg mirikizumab administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period.	Maintenance Period: Participants received 250 mg mirikizumab administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period.
Measure Participants	91	90	91
Number (95% Confidence Interval) [Percentage of participants]	18.7 17.5%	85.6 20.2%	84.6 16%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	66.7
	Confidence Interval	(2-Sided) 95%; 56.0 to 77.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W Responder to 250 mg Miri Q8W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	65.9
	Confidence Interval	(2-Sided) 95%; 54.9 to 77.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change in Palmoplantar Psoriasis Severity Index (PPASI) Total Score in Participants With Palmoplantar Involvement at Baseline
Description	The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. Least Squares Mean (LS Mean) was calculated using mixed model repeated measures (MMRM) model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as covariates.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had palmoplantar involvement at baseline.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	24	111
Least Squares Mean (Standard Error) [score on a scale]	-1.13 (1.29)	-5.83 (0.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.70
	Confidence Interval	(2-Sided) 95%; -7.31 to -2.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.32
	Estimation Comments

11. Secondary Outcome

Title	Change in Psoriasis Scalp Severity Index (PSSI) Total Score in Participants With Scalp Involvement at Baseline
Description	The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity). LS Mean was calculated using MMRM model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as covariates.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had scalp Involvement at baseline.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	94	381
Least Squares Mean (Standard Error) [score on a scale]	-2.70 (0.95)	-20.03 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-17.33
	Confidence Interval	(2-Sided) 95%; -19.28 to -15.39
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.99
	Estimation Comments

12. Secondary Outcome

Title	Change in Nail Psoriasis Severity Index (NAPSI) Total Score in Participants With Fingernail Involvement at Baseline
Description	The NAPSI scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix PsO by area of involvement. The fingernail is divided into quadrants. Each fingernail is given a score for fingernail bed PsO 0 (none) to 4 (PsO in 4 quadrants of the fingernail) and fingernail matrix PsO 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix PsO in each quadrant. The sum of all fingernails equals the total NAPSI score range is from 0 (no effect) to 80 (more severe psoriasis). LS Mean was calculated using MMRM model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as covariates.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had Nail Psoriasis involvement at baseline.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	64	248
Least Squares Mean (Standard Error) [score on a scale]	-2.04 (1.60)	-9.01 (0.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.98
	Confidence Interval	(2-Sided) 95%; -10.37 to -3.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.73
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline on the Short Form (SF)-36 Physical Component Summary (PCS)
Description	SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had a baseline and at least one post-baseline PCS value.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	106	418
Least Squares Mean (Standard Error) [score on a scale]	0.35 (0.69)	5.21 (0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.86
	Confidence Interval	(2-Sided) 95%; 3.50 to 6.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.69
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline on the SF-36 Mental Component Summary (MCS)
Description	SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had a baseline and at least one post-baseline MCS value.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	106	418
Least Squares Mean (Standard Error) [score on a scale]	0.32 (0.73)	5.10 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.78
	Confidence Interval	(2-Sided) 95%; 3.33 to 6.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.74
	Estimation Comments

15. Secondary Outcome

Title	Percentage of Participants With Patient's Global Assessment of Psoriasis (PatGA (0,1)) and >=2 Improvement From Baseline
Description	The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had a baseline >= 2.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	104	419
Number (95% Confidence Interval) [Percentage of participants]	1.0 0.9%	69.5 16.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	68.1
	Confidence Interval	(2-Sided) 95%; 63.2 to 72.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Change From Baseline on the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI-PSO)
Description	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism and impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100) with higher numbers indicating greater impairment and less productivity, that is, worse outcomes. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Induction Period:All randomized participants who had a baseline and at least one post-baseline WPAI-PSO value.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	106	418
Absenteeism	0.10 (1.87)	-3.57 (1.12)
Presenteeism	-4.54 (2.39)	-24.79 (1.42)
Overall Absenteeism and Presenteeism	-3.45 (2.82)	-24.54 (1.68)
Impairment in Activities Performed Outside of Work	-6.83 (2.27)	-29.73 (1.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments	Absenteeism
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.68
	Confidence Interval	(2-Sided) 95%; -7.30 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.84
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments	Presenteeism
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-20.24
	Confidence Interval	(2-Sided) 95%; -24.89 to -15.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.37
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments	Overall Absenteeism and Presenteeism
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-21.09
	Confidence Interval	(2-Sided) 95%; -26.56 to -15.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.78
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments	Impairment in Activities Performed Outside of Work
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-22.91
	Confidence Interval	(2-Sided) 95%; -27.39 to -18.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.28
	Estimation Comments

17. Secondary Outcome

Title	Change From Baseline in Quick Inventory of Depressive Symptomology (QIDS-SR16) Total Score in Those With a Baseline QIDS-SR16 Total Score ≥11
Description	QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. Whereas 0-5 indicates no symptoms. LS Mean was calculated using ANCOVA model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (<100 kg or >=100 kg), and geographic region (North America or Other) as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All participants who received at least one dose of study drug who had a baseline QIDS-SR16 total score >=11.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	10	35
Least Squares Mean (Standard Error) [score on a scale]	-4.95 (1.94)	-4.42 (1.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; -3.08 to 4.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.79
	Estimation Comments

18. Secondary Outcome

Title	Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) (0,1)
Description	The DLQI is a patient-reported, 10-question, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). A DLQI total score of 0 to 1 is considered as having no effect on a patient's health-related quality of life (HRQoL), and a 5-point change from baseline is considered as the minimal clinically important difference (MCID) threshold. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Induction Period: All randomized participants who had a baseline and at least one post-baseline DLQI value.

Arm/Group Title	Placebo Q4W	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	104	413
Number (95% Confidence Interval) [Percentage of participants]	8.7 8.1%	57.1 13.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Q4W, 250 mg Miri Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	48.8
	Confidence Interval	(2-Sided) 95%; 41.6 to 55.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Induction Period: Pharmacokinetics (PK): Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Mirikizumab at Week 16
Description	Minimum observed serum concentration at steady state (Ctrough,ss) of mirikizumab at Week 16.
Time Frame	Week 16: Day 113

Outcome Measure Data

Analysis Population Description

Induction Period: All participants who received at least one dose of study drug who had evaluable PK data.

Arm/Group Title	250 mg Miri Q4W
Arm/Group Description	Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Measure Participants	387
Geometric Mean (Geometric Coefficient of Variation) [micrograms per milliliter(micrograms/mL)]	2.00 (139)

Adverse Events

Time Frame	Baseline Up To 64 Weeks
Adverse Event Reporting Description	All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Arm/Group Title	Placebo Q4W		250 mg Miri Q4W		Placebo Q4W to Placebo Q8W (Placebo Responder)		Placebo Q4W to 250 mg Miri Q4W /Q8W (Placebo Non-Responders)		250 mg Miri Q4W Responders to Placebo Q8W		250 mg Miri Q4W Responders to 125 mg Miri Q8W		250 mg Miri Q4W Responder to 250 mg Miri Q8W		250mg Miri Q4W to 250mg Miri Q8W(Miri Non-Responders)		Relapse		Placebo Q4W to Placebo Q8W (Responder) Follow-up Period		Placebo Q4W Discontinued During Induction-Follow-up Period		Placebo Q4W to Placebo Non-Responder-Follow-up Period		250 mg Miri Q4W to Placebo Q8W (Responders) Follow-up Period		250mg Miri Q4W to 125 mg Miri Q8W(Responders) Follow-up Period		250mg Miri Q4W to 250mg Miri Q8W(Responders) Follow-up Period		250 Miri Q4W Discontinued During Induction-Follow-up		250 Miri Q4W to Miri Nonresponder-Follow-up Period
Arm/Group Description	Induction Period: Participants received placebo administered subcutaneously (SC) every 4 weeks (Q4W).		Induction Period: Participants received 250 mg mirikizumab (miri) administered SC Q4W.		Maintenance Period: Participants received placebo administered SC Q8W. Responders had ≥PASI 90. Participants had received placebo administered SC Q4W during induction period.		Maintenance Period: Participants received 250 mg mirikizumab administered SC Q4W during week 16 to week 32 and Q8W during week 40 and 48. Non-responders had < PASI 90. Participants had received placebo administered SC Q4W during induction period.		Maintenance Period: Participants received placebo administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period.		Maintenance Period: Participants received 125 mg mirikizumab administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period.		Maintenance Period: Participants received 250 mg mirikizumab administered SC Q8W. Responders had ≥PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period.		Maintenance Period: Participants received 250 mg mirikizumab administered SC Q8W. Non-responders had < PASI 90. Participants had received 250 mirikizumab administered SC Q4W during induction period.		Participants that relapsed were in the following arms: Placebo Q4W to Placebo Q8W (Placebo Responder). 250 mg Miri Q4W Responders to Placebo Q8W. 250 mg Miri Q4W Responders to 125 mg Miri Q8W. 250 mg Miri Q4W Responder to 250 mg Miri Q8W.		Follow-up Period: Participants did not receive drug during the follow-up period.		Follow-up Period: Participants did not receive drug during the follow-up period. Participants discontinued (DC) before induction week 16 and counted as placebo non-responders.		Follow-up Period: Participants did not receive drug during the follow-up period.		Follow-up Period: Participants did not receive drug during the follow-up period.		Follow-up Period: Participants did not receive drug during the follow-up period.		Follow-up Period: Participants did not receive drug during the follow-up period.		Follow-up Period: Participants did not receive drug during the follow-up period. Participants discontinued (DC) before induction week 16 and counted as miri non-responders.		Follow-up Period: Participants did not receive drug during the follow-up period.
All Cause Mortality
	Placebo Q4W		250 mg Miri Q4W		Placebo Q4W to Placebo Q8W (Placebo Responder)		Placebo Q4W to 250 mg Miri Q4W /Q8W (Placebo Non-Responders)		250 mg Miri Q4W Responders to Placebo Q8W		250 mg Miri Q4W Responders to 125 mg Miri Q8W		250 mg Miri Q4W Responder to 250 mg Miri Q8W		250mg Miri Q4W to 250mg Miri Q8W(Miri Non-Responders)		Relapse		Placebo Q4W to Placebo Q8W (Responder) Follow-up Period		Placebo Q4W Discontinued During Induction-Follow-up Period		Placebo Q4W to Placebo Non-Responder-Follow-up Period		250 mg Miri Q4W to Placebo Q8W (Responders) Follow-up Period		250mg Miri Q4W to 125 mg Miri Q8W(Responders) Follow-up Period		250mg Miri Q4W to 250mg Miri Q8W(Responders) Follow-up Period		250 Miri Q4W Discontinued During Induction-Follow-up		250 Miri Q4W to Miri Nonresponder-Follow-up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/422 (0%)		0/7 (0%)		0/94 (0%)		0/91 (0%)		0/90 (0%)		0/91 (0%)		0/140 (0%)		0/47 (0%)		0/1 (0%)		0/4 (0%)		0/6 (0%)		0/2 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)
Serious Adverse Events
	Placebo Q4W		250 mg Miri Q4W		Placebo Q4W to Placebo Q8W (Placebo Responder)		Placebo Q4W to 250 mg Miri Q4W /Q8W (Placebo Non-Responders)		250 mg Miri Q4W Responders to Placebo Q8W		250 mg Miri Q4W Responders to 125 mg Miri Q8W		250 mg Miri Q4W Responder to 250 mg Miri Q8W		250mg Miri Q4W to 250mg Miri Q8W(Miri Non-Responders)		Relapse		Placebo Q4W to Placebo Q8W (Responder) Follow-up Period		Placebo Q4W Discontinued During Induction-Follow-up Period		Placebo Q4W to Placebo Non-Responder-Follow-up Period		250 mg Miri Q4W to Placebo Q8W (Responders) Follow-up Period		250mg Miri Q4W to 125 mg Miri Q8W(Responders) Follow-up Period		250mg Miri Q4W to 250mg Miri Q8W(Responders) Follow-up Period		250 Miri Q4W Discontinued During Induction-Follow-up		250 Miri Q4W to Miri Nonresponder-Follow-up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/107 (1.9%)		5/422 (1.2%)		0/7 (0%)		0/94 (0%)		3/91 (3.3%)		1/90 (1.1%)		3/91 (3.3%)		0/140 (0%)		0/47 (0%)		0/1 (0%)		0/4 (0%)		0/6 (0%)		0/2 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)
Cardiac disorders
Acute myocardial infarction	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Atrial fibrillation	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hepatobiliary disorders
Bile duct stone	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cholecystitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Infections and infestations
Appendicitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Arthritis bacterial	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gastroenteritis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pharyngitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Injury, poisoning and procedural complications
Fall	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Ligament rupture	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Skull fracture	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Nervous system disorders
Cerebral infarction	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Epilepsy	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Subarachnoid haemorrhage	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Syncope	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Renal and urinary disorders
Glomerulonephritis membranous	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Surgical and medical procedures
Tonsillectomy	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo Q4W		250 mg Miri Q4W		Placebo Q4W to Placebo Q8W (Placebo Responder)		Placebo Q4W to 250 mg Miri Q4W /Q8W (Placebo Non-Responders)		250 mg Miri Q4W Responders to Placebo Q8W		250 mg Miri Q4W Responders to 125 mg Miri Q8W		250 mg Miri Q4W Responder to 250 mg Miri Q8W		250mg Miri Q4W to 250mg Miri Q8W(Miri Non-Responders)		Relapse		Placebo Q4W to Placebo Q8W (Responder) Follow-up Period		Placebo Q4W Discontinued During Induction-Follow-up Period		Placebo Q4W to Placebo Non-Responder-Follow-up Period		250 mg Miri Q4W to Placebo Q8W (Responders) Follow-up Period		250mg Miri Q4W to 125 mg Miri Q8W(Responders) Follow-up Period		250mg Miri Q4W to 250mg Miri Q8W(Responders) Follow-up Period		250 Miri Q4W Discontinued During Induction-Follow-up		250 Miri Q4W to Miri Nonresponder-Follow-up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/107 (47.7%)		199/422 (47.2%)		0/7 (0%)		0/94 (0%)		49/91 (53.8%)		61/90 (67.8%)		55/91 (60.4%)		0/140 (0%)		17/47 (36.2%)		0/1 (0%)		0/4 (0%)		0/6 (0%)		0/2 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)
Blood and lymphatic system disorders
Hilar lymphadenopathy	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Leukocytosis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Lymphadenopathy	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Thrombocytosis	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cardiac disorders
Acute myocardial infarction	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Bradycardia	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cardiac failure chronic	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Palpitations	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Ear and labyrinth disorders
Ear discomfort	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Ear pain	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tinnitus	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Vertigo	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Endocrine disorders
Goitre	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hypothyroidism	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Eye disorders
Blepharitis	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cataract	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cataract subcapsular	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Conjunctival haemorrhage	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Ocular hyperaemia	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Visual impairment	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Vitreous floaters	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Abdominal pain lower	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Abdominal pain upper	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Aphthous ulcer	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Chronic gastritis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Constipation	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Defaecation disorder	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dental caries	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Diarrhoea	0/107 (0%)	0	8/422 (1.9%)	9	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	3/91 (3.3%)	3	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dry mouth	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dyspepsia	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Enteritis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Faeces soft	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Food poisoning	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gastritis	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gastrointestinal disorder	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gastrooesophageal reflux disease	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gingival atrophy	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Glossitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Haemorrhoids	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Nausea	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Periodontal disease	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Stomatitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Toothache	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	6	2/90 (2.2%)	2	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Umbilical hernia	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Vomiting	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
General disorders
Chest pain	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Fat necrosis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Fatigue	1/107 (0.9%)	1	2/422 (0.5%)	3	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hyperthermia	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Influenza like illness	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Injection site erythema	0/107 (0%)	0	1/422 (0.2%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Injection site induration	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Injection site pain	5/107 (4.7%)	20	22/422 (5.2%)	109	0/7 (0%)	0	0/94 (0%)	0	2/91 (2.2%)	48	5/90 (5.6%)	49	6/91 (6.6%)	65	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Injection site pruritus	0/107 (0%)	0	2/422 (0.5%)	3	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Injection site reaction	0/107 (0%)	0	5/422 (1.2%)	11	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	2/90 (2.2%)	3	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Injection site swelling	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Malaise	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Oedema peripheral	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	2/90 (2.2%)	2	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pain	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pyrexia	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Xerosis	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cholelithiasis	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Drug-induced liver injury	0/107 (0%)	0	1/422 (0.2%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hepatic steatosis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	3/91 (3.3%)	3	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Immune system disorders
Allergy to arthropod bite	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Drug hypersensitivity	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hypersensitivity	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Infections and infestations
Abdominal wall abscess	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Acne pustular	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Acute sinusitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Bacterial infection	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Bacteriuria	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Body tinea	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Borrelia infection	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Bronchitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	2/90 (2.2%)	2	3/91 (3.3%)	4	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Carbuncle	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cellulitis	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Chronic sinusitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Conjunctivitis	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Conjunctivitis bacterial	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cystitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Ear infection	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Enterocolitis bacterial	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Epididymitis	0/74 (0%)	0	1/298 (0.3%)	1	0/3 (0%)	0	0/67 (0%)	0	0/61 (0%)	0	0/64 (0%)	0	0/59 (0%)	0	0/106 (0%)	0	0/31 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/9 (0%)	0
Erysipelas	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Erythema migrans	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Folliculitis	0/107 (0%)	0	5/422 (1.2%)	5	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	2/90 (2.2%)	2	1/91 (1.1%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gastroenteritis	1/107 (0.9%)	1	4/422 (0.9%)	4	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	3/91 (3.3%)	3	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gastroenteritis viral	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gastrointestinal infection	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Helicobacter gastritis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hepatitis a	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hepatitis e	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Herpes zoster	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hordeolum	0/107 (0%)	0	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Infected dermal cyst	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Influenza	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	3/91 (3.3%)	6	0/90 (0%)	0	3/91 (3.3%)	3	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Laryngitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Molluscum contagiosum	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Nasopharyngitis	14/107 (13.1%)	14	55/422 (13%)	61	0/7 (0%)	0	0/94 (0%)	0	15/91 (16.5%)	35	13/90 (14.4%)	16	9/91 (9.9%)	13	0/140 (0%)	0	2/47 (4.3%)	2	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Onychomycosis	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Oral herpes	0/107 (0%)	0	4/422 (0.9%)	4	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	2/90 (2.2%)	5	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Otitis media	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Otitis media acute	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Paronychia	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	2	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Parotitis	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pelvic inflammatory disease	0/33 (0%)	0	0/124 (0%)	0	0/4 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	1/26 (3.8%)	1	0/32 (0%)	0	0/34 (0%)	0	0/16 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Periodontitis	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pharyngitis	3/107 (2.8%)	3	7/422 (1.7%)	7	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	3/90 (3.3%)	3	4/91 (4.4%)	4	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pharyngitis streptococcal	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pharyngotonsillitis	1/107 (0.9%)	1	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pneumonia	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Postoperative wound infection	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pulpitis dental	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Respiratory tract infection	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Rhinitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Salpingo-oophoritis	0/33 (0%)	0	0/124 (0%)	0	0/4 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/26 (0%)	0	1/32 (3.1%)	1	0/34 (0%)	0	0/16 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Sinusitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Subcutaneous abscess	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tinea pedis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tinea versicolour	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tonsillitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tooth infection	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tracheitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Typhoid fever	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Upper respiratory tract infection	0/107 (0%)	0	16/422 (3.8%)	20	0/7 (0%)	0	0/94 (0%)	0	7/91 (7.7%)	17	5/90 (5.6%)	5	10/91 (11%)	11	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Urethritis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Urinary tract infection	1/107 (0.9%)	1	8/422 (1.9%)	10	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	3/90 (3.3%)	3	2/91 (2.2%)	2	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Vaginal infection	0/33 (0%)	0	1/124 (0.8%)	1	0/4 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/26 (0%)	0	0/32 (0%)	0	0/34 (0%)	0	1/16 (6.3%)	1	0/1 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Viral infection	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Vulvovaginal candidiasis	0/33 (0%)	0	1/124 (0.8%)	1	0/4 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/26 (0%)	0	0/32 (0%)	0	0/34 (0%)	0	0/16 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Injury, poisoning and procedural complications
Animal bite	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Ankle fracture	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Arthropod bite	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Arthropod sting	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Contusion	2/107 (1.9%)	2	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	2/90 (2.2%)	2	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Epicondylitis	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Fall	3/107 (2.8%)	3	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Foot fracture	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Ligament sprain	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Limb injury	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	2/91 (2.2%)	6	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Meniscus injury	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	2/90 (2.2%)	3	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Post concussion syndrome	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Procedural pain	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Rib fracture	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Skin abrasion	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Skin laceration	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Thermal burn	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Wound	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Wound complication	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Investigations
Alanine aminotransferase increased	2/107 (1.9%)	2	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	1	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Aspartate aminotransferase increased	1/107 (0.9%)	1	1/422 (0.2%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	2/91 (2.2%)	4	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Blood cholesterol increased	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	4	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Blood creatine phosphokinase increased	3/107 (2.8%)	3	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	2/91 (2.2%)	4	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Blood glucose increased	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Blood pressure increased	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	2/90 (2.2%)	3	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Blood triglycerides increased	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Blood urea increased	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Blood uric acid increased	1/107 (0.9%)	1	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
C-reactive protein increased	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Electrocardiogram qt prolonged	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Fibrin d dimer increased	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gamma-glutamyltransferase increased	1/107 (0.9%)	1	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Heart rate increased	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hepatic enzyme increased	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hepatitis b dna assay positive	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Liver function test abnormal	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Liver function test increased	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Lymphocyte count decreased	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Thyroxine free decreased	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Very low density lipoprotein increased	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Weight decreased	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Weight increased	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	2/90 (2.2%)	2	1/91 (1.1%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
White blood cell count increased	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Metabolism and nutrition disorders
Cardiometabolic syndrome	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Diabetes mellitus	0/107 (0%)	0	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dyslipidaemia	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	2/91 (2.2%)	3	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Gout	0/107 (0%)	0	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hypercholesterolaemia	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hyperglycaemia	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hyperlipidaemia	2/107 (1.9%)	2	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hypertriglyceridaemia	1/107 (0.9%)	1	5/422 (1.2%)	5	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	2/90 (2.2%)	2	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hyperuricaemia	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Increased appetite	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Overweight	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Type 2 diabetes mellitus	1/107 (0.9%)	1	5/422 (1.2%)	5	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	3/107 (2.8%)	3	10/422 (2.4%)	11	0/7 (0%)	0	0/94 (0%)	0	5/91 (5.5%)	12	3/90 (3.3%)	3	3/91 (3.3%)	3	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Arthritis	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Arthropathy	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Back pain	2/107 (1.9%)	2	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	3/91 (3.3%)	6	4/90 (4.4%)	4	2/91 (2.2%)	2	0/140 (0%)	0	2/47 (4.3%)	2	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Bursitis	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Costochondritis	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Enthesopathy	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Fasciitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Groin pain	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Intervertebral disc protrusion	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Joint effusion	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Joint swelling	1/107 (0.9%)	2	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Muscle spasms	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Muscle tightness	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Muscular weakness	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Musculoskeletal chest pain	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	2/90 (2.2%)	2	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Musculoskeletal pain	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Myalgia	0/107 (0%)	0	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Osteoarthritis	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	2/90 (2.2%)	2	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pain in extremity	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	2/90 (2.2%)	2	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Plantar fasciitis	1/107 (0.9%)	2	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Psoriatic arthropathy	1/107 (0.9%)	1	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Rotator cuff syndrome	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Spinal osteoarthritis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Spinal pain	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Synovial cyst	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tendonitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	4	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Basal cell carcinoma	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dysplastic naevus	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Fibroma	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Lipoma	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Skin papilloma	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	4	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Nervous system disorders
Cerebral infarction	0/107 (0%)	0	1/422 (0.2%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cervical radiculopathy	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dizziness	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Facial paralysis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Headache	5/107 (4.7%)	6	10/422 (2.4%)	10	0/7 (0%)	0	0/94 (0%)	0	2/91 (2.2%)	6	5/90 (5.6%)	9	4/91 (4.4%)	5	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hypoaesthesia	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Migraine	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Sciatica	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Sinus headache	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Somnolence	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Syncope	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Psychiatric disorders
Anxiety	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	4/91 (4.4%)	8	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Depressed mood	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	1/47 (2.1%)	1	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Depression	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Insomnia	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Irritability	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Libido decreased	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Sleep disorder	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tobacco abuse	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Renal and urinary disorders
Dysuria	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hydronephrosis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pollakiuria	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Reproductive system and breast disorders
Amenorrhoea	0/33 (0%)	0	0/124 (0%)	0	0/4 (0%)	0	0/27 (0%)	0	1/30 (3.3%)	2	0/26 (0%)	0	0/32 (0%)	0	0/34 (0%)	0	0/16 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Breast pain	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dysmenorrhoea	0/33 (0%)	0	0/124 (0%)	0	0/4 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	1/26 (3.8%)	1	1/32 (3.1%)	2	0/34 (0%)	0	0/16 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Erectile dysfunction	0/74 (0%)	0	0/298 (0%)	0	0/3 (0%)	0	0/67 (0%)	0	0/61 (0%)	0	0/64 (0%)	0	1/59 (1.7%)	1	0/106 (0%)	0	0/31 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/9 (0%)	0
Menstruation irregular	0/33 (0%)	0	0/124 (0%)	0	0/4 (0%)	0	0/27 (0%)	0	1/30 (3.3%)	2	0/26 (0%)	0	0/32 (0%)	0	0/34 (0%)	0	0/16 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Prostatitis	0/74 (0%)	0	1/298 (0.3%)	1	0/3 (0%)	0	0/67 (0%)	0	0/61 (0%)	0	0/64 (0%)	0	0/59 (0%)	0	0/106 (0%)	0	0/31 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/9 (0%)	0
Vaginal discharge	0/33 (0%)	0	1/124 (0.8%)	1	0/4 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/26 (0%)	0	0/32 (0%)	0	0/34 (0%)	0	0/16 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/2 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/107 (0%)	0	4/422 (0.9%)	4	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Cough	1/107 (0.9%)	1	9/422 (2.1%)	10	0/7 (0%)	0	0/94 (0%)	0	2/91 (2.2%)	4	2/90 (2.2%)	2	4/91 (4.4%)	4	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dyspnoea	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Emphysema	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Nasal congestion	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Oropharyngeal pain	1/107 (0.9%)	1	3/422 (0.7%)	4	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	1	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pulmonary mass	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Rhinitis allergic	0/107 (0%)	0	4/422 (0.9%)	4	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Rhinorrhoea	1/107 (0.9%)	1	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tonsillar hypertrophy	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Upper respiratory tract inflammation	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Upper-airway cough syndrome	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Vocal cord polyp	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Actinic keratosis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Alopecia areata	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Blister	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dermal cyst	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dermatitis contact	2/107 (1.9%)	3	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	3/90 (3.3%)	3	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dermatitis psoriasiform	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Diffuse alopecia	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Dyshidrotic eczema	0/107 (0%)	0	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Eczema	0/107 (0%)	0	3/422 (0.7%)	3	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Eczema asteatotic	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Erythema	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Ingrowing nail	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Intertrigo	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Perioral dermatitis	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Pruritus	3/107 (2.8%)	3	5/422 (1.2%)	5	0/7 (0%)	0	0/94 (0%)	0	4/91 (4.4%)	8	2/90 (2.2%)	3	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Psoriasis	1/107 (0.9%)	1	2/422 (0.5%)	2	0/7 (0%)	0	0/94 (0%)	0	1/91 (1.1%)	2	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Rash	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Rosacea	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Seborrhoeic dermatitis	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Skin fissures	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Urticaria	0/107 (0%)	0	4/422 (0.9%)	6	0/7 (0%)	0	0/94 (0%)	0	2/91 (2.2%)	6	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Surgical and medical procedures
Cataract operation	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Duodenal sphincterotomy	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Tooth extraction	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	1/91 (1.1%)	1	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Wisdom teeth removal	0/107 (0%)	0	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	1/90 (1.1%)	1	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Vascular disorders
Blood pressure fluctuation	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Essential hypertension	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Haematoma	1/107 (0.9%)	1	0/422 (0%)	0	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Hypertension	0/107 (0%)	0	9/422 (2.1%)	10	0/7 (0%)	0	0/94 (0%)	0	3/91 (3.3%)	6	3/90 (3.3%)	4	2/91 (2.2%)	2	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0
Varicose vein	0/107 (0%)	0	1/422 (0.2%)	1	0/7 (0%)	0	0/94 (0%)	0	0/91 (0%)	0	0/90 (0%)	0	0/91 (0%)	0	0/140 (0%)	0	0/47 (0%)	0	0/1 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/16 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.