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

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ClinicalTrials.gov Identifier: NCT03482011
Recruitment Status : Completed
First Posted : March 29, 2018
Results First Posted : September 25, 2020
Last Update Posted : September 25, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Psoriasis
Interventions Drug: Mirikizumab
Drug: Placebo
Enrollment 530
Recruitment Details  
Pre-assignment Details  
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)
Hide 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 [1] 0 [1] 0 [1] 0 [1] 0 [1] 0 [1]
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
Reason Not Completed
Adverse Event             1             3             0             0             0             0             0             0
Lack of Efficacy             3             1             0             0             0             0             0             0
Lost to Follow-up             0             1             0             0             0             0             0             0
Screen Failure             0             1             0             0             0             0             0             0
Withdrawal by Subject             2             5             0             0             0             0             0             0
[1]
Participants were assigned to this arm during maintenance period.
Period Title: Maintenance Period (36 Weeks)
Started 0 [1] 0 [1] 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
Reason Not Completed
Adverse Event             0             0             0             0             0             1             1             4
Lack of Efficacy             0             0             1             2             1             1             0             9
Lost to Follow-up             0             0             0             0             2             0             0             1
Physician Decision             0             0             0             1             0             1             1             1
Withdrawal by Subject             0             0             0             1             2             1             2             2
[1]
Participants were assigned to this arm during induction period.
Period Title: Follow-up Period (12 Weeks)
Started 0 [1] 0 [1] 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
Reason Not Completed
Withdrawal by Subject             0             0             0             2             0             1             1             5
Adverse Event             0             0             0             0             0             0             1             4
Lack of Efficacy             0             0             1             3             0             0             0             6
Physician Decision             0             0             0             0             0             0             0             1
Lost to Follow-up             0             0             0             0             0             0             0             1
[1]
Participants were assigned to this arm during induction period.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W Total
Hide 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 Number of Baseline Participants 107 423 530
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 107 participants 423 participants 530 participants
45.7  (13.70) 46.4  (13.56) 46.3  (13.58)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 423 participants 530 participants
Female 33 124 157
Male 74 299 373
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 423 participants 530 participants
Hispanic or Latino 4 13 17
Not Hispanic or Latino 11 53 64
Unknown or Not Reported 92 357 449
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 423 participants 530 participants
American Indian or Alaska Native 14 50 64
Asian 33 139 172
Native Hawaiian or Other Pacific Islander 0 1 1
Black or African American 4 2 6
White 56 231 287
More than one race 0 0 0
Unknown or Not Reported 0 0 0
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 423 participants 530 participants
South Korea 11 45 56
Puerto Rico 5 15 20
United States 16 69 85
Japan 10 44 54
Taiwan 12 49 61
Poland 11 44 55
Mexico 15 61 76
Germany 16 58 74
Russia 11 38 49
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 107 423
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
6.5
(1.9 to 11.2)
69.3
(64.9 to 73.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 63.0
Confidence Interval (2-Sided) 95%
56.5 to 69.4
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Achieving a ≥90% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 90)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 107 423
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
6.5
(1.9 to 11.2)
64.3
(59.7 to 68.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 57.8
Confidence Interval (2-Sided) 95%
51.3 to 64.4
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Achieving a ≥75% Improvement From Baseline in PASI (PASI 75)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 107 423
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0.9
(0.0 to 2.8)
17.0
(13.4 to 20.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 15.6
Confidence Interval (2-Sided) 95%
11.6 to 19.7
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving a ≥75% Improvement From Baseline in PASI (PASI 75)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 107 423
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
9.3
(3.8 to 14.9)
82.5
(78.9 to 86.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 73.6
Confidence Interval (2-Sided) 95%
67.1 to 80.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Achieving a ≥100% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 100)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 107 423
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0.9
(0.0 to 2.8)
32.4
(27.9 to 36.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 30.8
Confidence Interval (2-Sided) 95%
26.0 to 35.7
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With ≤1% of Body Surface Area (BSA) With Psoriasis Involvement
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period:All randomized participants.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 107 423
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0.9
(0.0 to 2.8)
49.2
(44.4 to 53.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 48.1
Confidence Interval (2-Sided) 95%
42.9 to 53.2
Estimation Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 105 410
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0
(0.0 to 0.0)
19.0
(15.2 to 22.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 18.3
Confidence Interval (2-Sided) 95%
14.5 to 22.1
Estimation Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 92 384
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
5.4
(0.8 to 10.1)
54.7
(49.7 to 59.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 49.6
Confidence Interval (2-Sided) 95%
42.8 to 56.4
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants Maintaining Clinical Response (PASI 90) After Re-randomization at the Start of the Randomized Withdrawal Period
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.

Overall Number of Participants Analyzed 91 90 91
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
18.7
(10.7 to 26.7)
85.6
(78.3 to 92.8)
84.6
(77.2 to 92.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 250 mg Miri Q4W Responders to Placebo Q8W, 250 mg Miri Q4W Responders to 125 mg Miri Q8W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 66.7
Confidence Interval (2-Sided) 95%
56.0 to 77.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 250 mg Miri Q4W Responders to Placebo Q8W, 250 mg Miri Q4W Responder to 250 mg Miri Q8W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 65.9
Confidence Interval (2-Sided) 95%
54.9 to 77.0
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in Palmoplantar Psoriasis Severity Index (PPASI) Total Score in Participants With Palmoplantar Involvement at Baseline
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants who had palmoplantar involvement at baseline.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 24 111
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.13  (1.29) -5.83  (0.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
11.Secondary Outcome
Title Change in Psoriasis Scalp Severity Index (PSSI) Total Score in Participants With Scalp Involvement at Baseline
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants who had scalp Involvement at baseline.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 94 381
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.70  (0.95) -20.03  (0.55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
12.Secondary Outcome
Title Change in Nail Psoriasis Severity Index (NAPSI) Total Score in Participants With Fingernail Involvement at Baseline
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants who had Nail Psoriasis involvement at baseline.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 64 248
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.04  (1.60) -9.01  (0.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
13.Secondary Outcome
Title Change From Baseline on the Short Form (SF)-36 Physical Component Summary (PCS)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 106 418
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
0.35  (0.69) 5.21  (0.43)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
14.Secondary Outcome
Title Change From Baseline on the SF-36 Mental Component Summary (MCS)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 106 418
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
0.32  (0.73) 5.10  (0.46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With Patient's Global Assessment of Psoriasis (PatGA (0,1)) and >=2 Improvement From Baseline
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Period: All randomized participants who had a baseline >= 2.
Arm/Group Title Placebo Q4W 250 mg Miri Q4W
Hide 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.
Overall Number of Participants Analyzed 104 419
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
1.0
(0.0 to 2.8)
69.5
(65.0 to 73.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 68.1
Confidence Interval (2-Sided) 95%
63.2 to 72.9
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline on the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI-PSO)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 106 418
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Absenteeism Number Analyzed 65 participants 277 participants
0.10  (1.87) -3.57  (1.12)
Presenteeism Number Analyzed 64 participants 271 participants
-4.54  (2.39) -24.79  (1.42)
Overall Absenteeism and Presenteeism Number Analyzed 64 participants 271 participants
-3.45  (2.82) -24.54  (1.68)
Impairment in Activities Performed Outside of Work Number Analyzed 106 participants 418 participants
-6.83  (2.27) -29.73  (1.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments Absenteeism
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
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 [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments Presenteeism
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 10 35
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-4.95  (1.94) -4.42  (1.43)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
18.Secondary Outcome
Title Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) (0,1)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 104 413
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
8.7
(3.3 to 14.1)
57.1
(52.4 to 61.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q4W, 250 mg Miri Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 48.8
Confidence Interval (2-Sided) 95%
41.6 to 55.9
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Induction Period: Pharmacokinetics (PK): Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Mirikizumab at Week 16
Hide Description Minimum observed serum concentration at steady state (Ctrough,ss) of mirikizumab at Week 16.
Time Frame Week 16: Day 113
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Induction Period: Participants received 250 mg mirikizumab administered SC Q4W.
Overall Number of Participants Analyzed 387
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms per milliliter(micrograms/mL)
2.00
(139%)
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/107 (0.00%)      0/422 (0.00%)      0/7 (0.00%)      0/94 (0.00%)      0/91 (0.00%)      0/90 (0.00%)      0/91 (0.00%)      0/140 (0.00%)      0/47 (0.00%)      0/1 (0.00%)      0/4 (0.00%)      0/6 (0.00%)      0/2 (0.00%)      0/4 (0.00%)      0/4 (0.00%)      0/5 (0.00%)      0/16 (0.00%)    
Hide 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 (1.87%)      5/422 (1.18%)      0/7 (0.00%)      0/94 (0.00%)      3/91 (3.30%)      1/90 (1.11%)      3/91 (3.30%)      0/140 (0.00%)      0/47 (0.00%)      0/1 (0.00%)      0/4 (0.00%)      0/6 (0.00%)      0/2 (0.00%)      0/4 (0.00%)      0/4 (0.00%)      0/5 (0.00%)      0/16 (0.00%)    
Cardiac disorders                                   
Acute myocardial infarction  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Atrial fibrillation  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Hepatobiliary disorders                                   
Bile duct stone  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Cholecystitis  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Infections and infestations                                   
Appendicitis  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Arthritis bacterial  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Gastroenteritis  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Pharyngitis  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Injury, poisoning and procedural complications                                   
Fall  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Ligament rupture  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Skull fracture  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Nervous system disorders                                   
Cerebral infarction  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Epilepsy  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Subarachnoid haemorrhage  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Syncope  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Renal and urinary disorders                                   
Glomerulonephritis membranous  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Surgical and medical procedures                                   
Tonsillectomy  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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 (47.66%)      199/422 (47.16%)      0/7 (0.00%)      0/94 (0.00%)      49/91 (53.85%)      61/90 (67.78%)      55/91 (60.44%)      0/140 (0.00%)      17/47 (36.17%)      0/1 (0.00%)      0/4 (0.00%)      0/6 (0.00%)      0/2 (0.00%)      0/4 (0.00%)      0/4 (0.00%)      0/5 (0.00%)      0/16 (0.00%)    
Blood and lymphatic system disorders                                   
Hilar lymphadenopathy  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Leukocytosis  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Lymphadenopathy  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Thrombocytosis  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Cardiac disorders                                   
Acute myocardial infarction  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Bradycardia  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Cardiac failure chronic  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Palpitations  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Ear and labyrinth disorders                                   
Ear discomfort  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 1/47 (2.13%)  1 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Ear pain  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Tinnitus  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Vertigo  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Endocrine disorders                                   
Goitre  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 1/47 (2.13%)  1 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Hypothyroidism  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Eye disorders                                   
Blepharitis  1  0/107 (0.00%)  0 2/422 (0.47%)  2 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Cataract  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Cataract subcapsular  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Conjunctival haemorrhage  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Ocular hyperaemia  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 1/47 (2.13%)  1 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Visual impairment  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Vitreous floaters  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Gastrointestinal disorders                                   
Abdominal pain  1  1/107 (0.93%)  1 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Abdominal pain lower  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Abdominal pain upper  1  0/107 (0.00%)  0 2/422 (0.47%)  2 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Aphthous ulcer  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Chronic gastritis  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Constipation  1  1/107 (0.93%)  1 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Defaecation disorder  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Dental caries  1  0/107 (0.00%)  0 2/422 (0.47%)  2 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Diarrhoea  1  0/107 (0.00%)  0 8/422 (1.90%)  9 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 3/91 (3.30%)  3 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Dry mouth  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Dyspepsia  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Enteritis  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Faeces soft  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Food poisoning  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Gastritis  1  0/107 (0.00%)  0 2/422 (0.47%)  2 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Gastrointestinal disorder  1  1/107 (0.93%)  1 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Gastrooesophageal reflux disease  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Gingival atrophy  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Glossitis  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Haemorrhoids  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Nausea  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Periodontal disease  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Stomatitis  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Toothache  1  1/107 (0.93%)  1 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  6 2/90 (2.22%)  2 2/91 (2.20%)  2 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Umbilical hernia  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Vomiting  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
General disorders                                   
Chest pain  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Fat necrosis  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Fatigue  1  1/107 (0.93%)  1 2/422 (0.47%)  3 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Hyperthermia  1  1/107 (0.93%)  1 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Influenza like illness  1  0/107 (0.00%)  0 1/422 (0.24%)  1 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Injection site erythema  1  0/107 (0.00%)  0 1/422 (0.24%)  2 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Injection site induration  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Injection site pain  1  5/107 (4.67%)  20 22/422 (5.21%)  109 0/7 (0.00%)  0 0/94 (0.00%)  0 2/91 (2.20%)  48 5/90 (5.56%)  49 6/91 (6.59%)  65 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Injection site pruritus  1  0/107 (0.00%)  0 2/422 (0.47%)  3 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Injection site reaction  1  0/107 (0.00%)  0 5/422 (1.18%)  11 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 2/90 (2.22%)  3 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Injection site swelling  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Malaise  1  0/107 (0.00%)  0 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 2/91 (2.20%)  2 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/16 (0.00%)  0
Oedema peripheral  1  1/107 (0.93%)  1 0/422 (0.00%)  0 0/7 (0.00%)  0 0/94 (0.00%)  0 1/91 (1.10%)  2 2/90 (2.22%)  2 0/91 (0.00%)  0 0/140 (0.00%)  0 0/47 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0