Long-Term Safety Evaluation of Dupilumab in Patients With Asthma (LIBERTY ASTHMA TRAVERSE)
Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT02134028
Collaborator
Regeneron Pharmaceuticals (Industry)
2,282
365
1
62.2
6.3
0.1
Study Details
Study Description
Brief Summary
Primary Objective:
To evaluate the long-term safety and tolerability of dupilumab in participants with asthma who participated in a previous dupilumab asthma study (DRI12544, PDY14192, EFC13579, EFC13691).
Secondary Objectives:
To evaluate the long-term efficacy of dupilumab in participants with asthma who participated in a previous dupilumab asthma clinical study.
To evaluate dupilumab in participants with asthma who participated in a previous dupilumab asthma clinical study, with regards to:
-
Systemic exposure
-
Anti-drug antibodies
-
Biomarkers
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
A screening period, up to 3 weeks, applied only for participants who came from DRI12544 study. The total study duration, per participant, was a maximum of 108 weeks (or 111 weeks considering a maximum screening period of 3 weeks for study DRI12544) for the participants enrolled prior to Amendment 04 approval and a maximum of 60 weeks for the participants enrolled after Amendment 04 approval.
Following amendment 04 (dated 31 Oct 2016) the open-label treatment duration was amended to 48 weeks (1 year); and the 16-week post-treatment period was shortened to 12 weeks.
Study Design
Study Type:
Interventional
Actual Enrollment
:
2282 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Dupilumab in Patients With Asthma Who Participated in a Previous Dupilumab Asthma Clinical Study
Actual Study Start Date
:
Aug 5, 2014
Actual Primary Completion Date
:
Oct 11, 2019
Actual Study Completion Date
:
Oct 11, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: dupilumab treatment For participants coming from the DRI12544 study: dupilumab loading dose subcutaneous (SC) on Day 1, followed by 1* Dose every 2 weeks added to current controller medications. For participants coming from other studies: dupilumab 1 * Dose SC every 2 weeks added to current controller medications. |
Drug: Dupilumab
Pharmaceutical form: Solution for injection Routes of administration: Subcutaneous
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks (up to 108 weeks)]
An Adverse Event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that developed, worsened, or became serious during the treatment emergent AE period (time from first dose of investigational medicinal product [IMP] in LTS12551 up to the last dose of dupilumab plus 14 weeks). A Serious AE (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Secondary Outcome Measures
- Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities During the TEAE Period [From the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks (up to 108 weeks)]
Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure (SBP): Less than or equal to (≤) 95 Adults (≤90 Adolescents) millimeters of mercury (mmHg) and decrease from baseline (DFB) greater than or equal to (≥) 20 mmHg; ≥ 160 Adults (≥ 119 Adolescents) mmHg and increase from baseline (IFB) ≥ 20 mmHg. Diastolic blood pressure (DBP): ≤ 45 Adults (≤54 Adolescents) mmHg and DFB ≥ 10 mmHg; ≥ 110 Adults (≥78 Adolescents) mmHg and IFB ≥ 10 mmHg. Heart rate (HR): ≤ 50 beats per minute (bpm) and DFB ≥ 20 bpm; ≥ 120 bpm and IFB ≥ 20 bpm. Respiratory rate: less than (<) 12 breaths/min(b/m); greater than (>) 20 b/m. Weight (kg): ≥ 5 percent (%) DFB; ≥ 5% IFB. Temperature: ≥ 38.0 degree Celsius (°C) rectal/ear/temporal; ≥ 37.5°C oral; ≥ 37.2°C axillary. TEAE period was defined as the time from first dose of IMP in LTS12551 up to the last dose of dupilumab plus 14 weeks.
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters (Red Blood Cells [RBCs], Platelets and Coagulation) During the TEAE Period [From the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks (up to 108 weeks)]
Criteria for potentially clinically significant abnormalities: Hemoglobin (Hb): ≤ 115 grams per liter (g/L)(Male [M]), ≤ 95 g/L (Female[ F]) (< 100 g/L Adolescents); ≥ 185 g/L (M), ≥ 165 g/L (F) (≥ 200 g/L Adolescents); DFB ≥ 20 g/L. Hematocrit: ≤ 0.37 volume/volume (v/v) (M); ≤ 0.32 v/v (F) (<0.32 v/v Adolescents); ≥ 0.55 v/v (M); 0.5 v/v (F) (>0.47 v/v Adolescents). RBCs: ≥ 6 Tera/L. Platelets: < 100 Giga(G)/L; ≥ 700 G/L. TEAE period was defined as the time from first dose of IMP in LTS12551 up to the last dose of dupilumab plus 14 weeks.
- Number of Severe Exacerbation Events [From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks)]
Severe asthma exacerbation events were defined as a deterioration of asthma which required: use of systemic corticosteroids for ≥ 3 days, (participants from study EFC13691 (NCT02528214), and who were taking systemic corticosteroids: the use of systemic corticosteroids at least double the current dose and for ≥3 days.) or, hospitalization or emergency room visit because of asthma, required systemic corticosteroids.
- Annualized Event Rate Per Participant-Years for Severe Exacerbation [From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks)]
The annualized event rate per participant-years was defined as the total number of events that occurred during the treatment period divided by the total number of participant-years during the treatment period.
- Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 48 and 96 [Baseline of parent study, Week 48 and Week 96 of this extension study]
FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. For this analysis, baseline was defined as respective parent study baseline.
- Change From Baseline in Percent Predicted FEV1 at Weeks 48 and 96 [Baseline of parent study, Week 48 and Week 96 of this extension study]
FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. For this analysis, baseline was defined as respective parent study baseline.
- Change From Baseline in Forced Vital Capacity (FVC) at Weeks 48 and 96 [Baseline of parent study, Week 48, and Week 96 of this extension study]
FVC was a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. For this analysis, baseline was defined as respective parent study baseline.
- Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 48 and 96 [Baseline of parent study, Week 48, and Week 96 of this extension study]
FEF was the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. For this analysis, baseline was defined as respective parent study baseline.
- Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Mean Scores at Weeks 24 and 48 [Baseline of parent study, Weeks 24, and 48 of this extension study]
The ACQ-5 had 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total mean score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), higher scores indicated lower asthma control. For this analysis, baseline was defined as respective parent study baseline.
- Percentage of Participants Achieving ACQ-5 Score Response (ACQ-5 Responders) at Weeks 24 and 48 [At Weeks 24, and 48 of this extension study]
ACQ-5 response was defined as change from baseline in ACQ-5 scores ≥ 0.5. The ACQ-5 had 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 mean total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control.
- Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Scores at Weeks 24 and 48 [Baseline of parent study, Weeks 24, and 48 of this extension study]
The AQLQ was designed to measure the functional impairments that are most troublesome to adults as a result of their asthma. The AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), and environmental stimuli (4 items). Each item was scored on a 7-point likert scale ranged from 1=severely impaired to 7=not impaired. The 32 items of the questionnaire were averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired); higher scores indicated better quality of life. For this analysis, baseline was defined as respective parent study baseline.
- Percentage of Participants Achieving AQLQ Global Score Response (AQLQ Responders) at Weeks 24 and 48 [At Weeks 24, and 48 of this extension study]
AQLQ global response was defined as participants with change from baseline in AQLQ global score ≥ 0.5. The AQLQ was designed to measure the functional impairments that are most troublesome to adults as a result of their asthma. The AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item was scored on a 7-point likert scale (1=severely impaired, 7=not impaired). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired). Higher scores indicated better quality of life.
- Serum Concentrations of Dupilumab Over Time Till Week 96 [Baseline of parent study, Weeks 0, 4, 12, 24, 48, 72, and 96 of this extension study]
For this analysis, baseline was defined as respective parent study baseline. Here, 'number analyzed'=number of participants with available data for each specified category.
- Percentage of Participants With Antidrug Antibodies (ADA) Response [From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks)]
ADA response were categorized as: treatment emergent and treatment boosted response. 1) Treatment emergent was defined as an ADA positive response in the assay post first dose in LTS12551, when baseline results were negative or missing. 2) Treatment boosted was defined as: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive. The criteria for positive was defined as "30 to > 10,000", where low titer (< 1,000); moderate (1,000 ≤ titer ≤ 10,000) and high titer (> 10,000).
- Change From Baseline in Blood Eosinophils Cells Count at Weeks 48 and 96 [Baseline of parent study, Week 48 and Week 96 of this extension study]
For this analysis, baseline was defined as respective parent study baseline.
- Change From Baseline in Morning Peak Expiratory Flow (PEF) at Weeks 48 and 96: Participants From Study DRI12544 [Baseline of parent study, Week 48 and Week 96 of this extension study]
The PEF was a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at morning and evening. Morning PEF was performed within 15 minutes after arising (between 5:30 AM and 10 AM) prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol. For this analysis, baseline was defined as parent study DRI12544 baseline.
- Change From Baseline in Evening Peak Expiratory Flow (PEF) at Weeks 48 and 96: Participants From Study DRI12544 [Baseline of parent study, Week 48 and Week 96 of this extension study]
The PEF was a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at morning and evening. Evening PEF was performed in the evening (between 5:30 PM and 10 PM) prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol. For this analysis, baseline was defined as parent DRI12544 study baseline.
- Change From Baseline in Morning Asthma Symptom Scores at Weeks 48 and 96: Participants From Study DRI12544 [Baseline of parent study, Week 48 and Week 96 of this extension study]
Morning asthma symptom score was determined using AM (ante meridiem) symptom scoring system which evaluated participant's overall asthma symptoms experienced during the night. It ranges from 0 to 4 as: 0=no asthma symptoms, slept through the night, 1=slept well, but some complaints in the morning. No nighttime awakenings, 2=woke up once because of asthma (including early awakening), 3=woke up several times because of asthma (including early awakening), 4=bad night, awake most of the night because of asthma; higher scores indicated more severe symptoms. For this analysis, baseline was defined as parent DRI12544 study baseline.
- Change From Baseline in Evening Asthma Symptom Scores at Weeks 48 and 96: Participants From Study DRI12544 [Baseline of parent study, Week 48, and Week 96 of this extension study]
Evening asthma symptom score was determined using PM (post meridiem) symptom scoring system which evaluated participant's overall asthma symptoms experienced during the day. It ranged from 0 to 4 as: 0=very well, no asthma symptoms, 1=one episode of wheezing, cough, or breathlessness, 2=more than one episode of wheezing, cough, or breathlessness without interference of normal activities, 3=wheezing, cough, or breathlessness most of the day, which interfered to some extent with normal activities, 4=asthma very bad, unable to carry out daily activities as usual; higher scores indicated more severe symptoms. For this analysis, baseline was defined as parent DRI12544 study baseline.
- Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol for Symptom Relief at Weeks 48 and 96: Participants From Study DRI12544 [Baseline of parent study, Week 48, and Week 96 of this extension study]
The number of salbutamol/albuterol or levosalbutamol/levalbuterol inhalations was recorded daily by the participants in an electronic diary/PEF meter. Mean number of inhalations in last 7 days prior to each visit was calculated and was used in computation of data reported. For this analysis, baseline was defined as parent DRI12544 study baseline.
- Change From Baseline in Number of Nocturnal Awakenings at Weeks 48 and 96: Participants From Study DRI12544 [Baseline of parent study, Week 48 and Week 96 of this extension study]
The number of nocturnal awakening because of asthma symptoms were recorded every morning by the participants in an electronic diary. Mean number of awakenings in last 7 days prior to each visit was calculated and was used in computation of data reported. For this analysis, baseline was defined as parent DRI12544 study baseline.
- Percent Change From Baseline in Oral Corticosteroid (OCS) Dose at Weeks 48, and 96: Participants From Study EFC13691 [Baseline of parent study, Weeks 48 and 96 of this extension study]
OCS was allowed as background controller medication for the participants from study EFC13691 only. For this analysis, baseline was defined as parent study EFC13691 baseline.
- Percentage of Participants Achieving a Reduction of 50% or Greater (≥ 50% ) in OCS Dose Over Time at Weeks 48 and 96: Participants From Study EFC13691 [Weeks 48 and 96 of this extension study]
OCS was allowed as background controller medication for the participants from study EFC13691 only. Percentage of participants who achieved a reduction of ≥ 50% in OCS dose were reported.
- Percentage of Participants With Background OCS Completely Tapered Off Over Time at Weeks 48 and 96: Participants From Study EFC13691 [Weeks 48, and 96 of this extension study]
OCS was allowed as background controller medication for the participants from study EFC13691 only. Number of participants who gradually discontinued or reduced therapeutic dose were reported in this outcome measure.
- Change From Baseline in European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Scores at Weeks 48 and 96: Participants From Study DRI12544 [Baseline of parent study, Week 48 and Week 96 of this extension study]
EQ-5D-3L: validated and reliable self-report health status questionnaire consisted of EQ-5D descriptive system and visual analogue scale (VAS). EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: no problem, some problems, and severe problems. The 5 dimensional 3-level systems was converted into single index utility score, and the score was 0 - 100, where 100=best health state; and 0=worst health state; where higher scores indicated better outcome. For this analysis, baseline was defined as parent DRI12544 study baseline.
- Change From Baseline in EQ-5D-3L VAS Scores at Weeks 48 and 96: Participants From Study DRI12544 [Baseline of parent study, Week 48 and Week 96 of this extension study]
EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0=worst imaginable health state and 100=best imaginable health state, where higher states indicated better outcomes. For this analysis, baseline was defined as parent DRI12544 study baseline.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
- Participants with asthma who completed the treatment period in a previous dupilumab asthma clinical study (i.e., PDY14192, EFC13579 or EFC13691) or participants with asthma who completed the treatment and follow-up periods in previous dupilumab asthma Study DRI12544.
Exclusion criteria:
- Participants who experienced any hypersensitivity reactions to Investigational Medicinal Product (IMP) in the previous dupilumab asthma study, which, in the opinion of the Investigator, could indicate that continued treatment with dupilumab, may present an unreasonable risk for the participant.
The above information was not intended to contain all considerations relevant to a Participant's potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 840047 | Birmingham | Alabama | United States | 35209 |
| 2 | Investigational Site Number 840099 | Gilbert | Arizona | United States | 85234 |
| 3 | Investigational Site Number 840087 | Scottsdale | Arizona | United States | 85251 |
| 4 | Investigational Site Number 840402 | Tucson | Arizona | United States | 85724 |
| 5 | Investigational Site Number 840132 | Little Rock | Arkansas | United States | 72209 |
| 6 | Investigational Site Number 840109 | Bakersfield | California | United States | 93301 |
| 7 | Investigational Site Number 840045 | Long Beach | California | United States | 90720 |
| 8 | Investigational Site Number 840019 | Los Angeles | California | United States | 90025 |
| 9 | Investigational Site Number 840029 | Los Angeles | California | United States | 90025 |
| 10 | Investigational Site Number 840022 | Los Angeles | California | United States | 90048 |
| 11 | Investigational Site Number 840044 | Newport Beach | California | United States | 92663 |
| 12 | Investigational Site Number 840041 | North Hollywood | California | United States | 91606 |
| 13 | Investigational Site Number 840014 | Rolling Hills Estates | California | United States | 90274 |
| 14 | Investigational Site Number 840121 | San Jose | California | United States | 95117 |
| 15 | Investigational Site Number 840040 | Colorado Springs | Colorado | United States | 80907 |
| 16 | Investigational Site Number 840403 | Denver | Colorado | United States | 80206 |
| 17 | Investigational Site Number 840006 | Denver | Colorado | United States | 80230 |
| 18 | Investigational Site Number 840024 | Denver | Colorado | United States | 80230 |
| 19 | Investigational Site Number 840130 | Denver | Colorado | United States | 80246 |
| 20 | Investigational Site Number 840902 | New Haven | Connecticut | United States | 06510 |
| 21 | Investigational Site Number 840137 | Aventura | Florida | United States | 33180 |
| 22 | Investigational Site Number 840071 | Gainesville | Florida | United States | 32607 |
| 23 | Investigational Site Number 840115 | Ocoee | Florida | United States | 34761 |
| 24 | Investigational Site Number 840055 | Sarasota | Florida | United States | 34239 |
| 25 | Investigational Site Number 840079 | Twin Falls | Idaho | United States | 83301 |
| 26 | Investigational Site Number 840101 | Chicago | Illinois | United States | 60611 |
| 27 | Investigational Site Number 840032 | Fort Mitchell | Kentucky | United States | 41017 |
| 28 | Investigational Site Number 840017 | Louisville | Kentucky | United States | 40223-5440 |
| 29 | Investigational Site Number 840030 | Owensboro | Kentucky | United States | 42301 |
| 30 | Investigational Site Number 840064 | Bangor | Maine | United States | 04401 |
| 31 | Investigational Site Number 840052 | Chevy Chase | Maryland | United States | 20815 |
| 32 | Investigational Site Number 840073 | Gaithersburg | Maryland | United States | 20878 |
| 33 | Investigational Site Number 840080 | Owings Mills | Maryland | United States | 21117 |
| 34 | Investigational Site Number 840401 | Boston | Massachusetts | United States | 02115 |
| 35 | Investigational Site Number 840018 | Minneapolis | Minnesota | United States | 55402 |
| 36 | Investigational Site Number 840002 | Saint Louis | Missouri | United States | 63110 |
| 37 | Investigational Site Number 840102 | Saint Louis | Missouri | United States | 63141 |
| 38 | Investigational Site Number 840093 | Saint Louis | Missouri | United States | |
| 39 | Investigational Site Number 840037 | Missoula | Montana | United States | 59808 |
| 40 | Investigational Site Number 840078 | Omaha | Nebraska | United States | 68124 |
| 41 | Investigational Site Number 840004 | Papillion | Nebraska | United States | 27103 |
| 42 | Investigational Site Number 840111 | Brick | New Jersey | United States | 08723 |
| 43 | Investigational Site Number 840068 | Ocean City | New Jersey | United States | 07712 |
| 44 | Investigational Site Number 840011 | Princeton | New Jersey | United States | 08540 |
| 45 | Investigational Site Number 840065 | New York | New York | United States | 10029 |
| 46 | Investigational Site Number 840126 | Charlotte | North Carolina | United States | 28226 |
| 47 | Investigational Site Number 840083 | Charlotte | North Carolina | United States | 28277 |
| 48 | Investigational Site Number 840108 | Durham | North Carolina | United States | 27705 |
| 49 | Investigational Site Number 840107 | Greensboro | North Carolina | United States | 27401 |
| 50 | Investigational Site Number 840907 | High Point | North Carolina | United States | 27262 |
| 51 | Investigational Site Number 840404 | Winston-Salem | North Carolina | United States | 27157-1071 |
| 52 | Investigational Site Number 840015 | Cincinnati | Ohio | United States | 45236 |
| 53 | Investigational Site Number 840146 | Cincinnati | Ohio | United States | 45241 |
| 54 | Investigational Site Number 840049 | Middleburg Heights | Ohio | United States | 44130 |
| 55 | Investigational Site Number 840942 | Toledo | Ohio | United States | 43617 |
| 56 | Investigational Site Number 840112 | Edmond | Oklahoma | United States | 73034 |
| 57 | Investigational Site Number 840104 | Tulsa | Oklahoma | United States | 74136 |
| 58 | Investigational Site Number 840034 | Medford | Oregon | United States | 97504 |
| 59 | Investigational Site Number 840031 | Portland | Oregon | United States | 97223 |
| 60 | Investigational Site Number 840046 | Bethlehem | Pennsylvania | United States | 18020 |
| 61 | Investigational Site Number 840085 | Hershey | Pennsylvania | United States | 17033 |
| 62 | Investigational Site Number 840067 | Philadelphia | Pennsylvania | United States | 19140 |
| 63 | Investigational Site Number 840928 | Pittsburgh | Pennsylvania | United States | 15213 |
| 64 | Investigational Site Number 840091 | Pittsburgh | Pennsylvania | United States | 15241 |
| 65 | Investigational Site Number 840082 | Charleston | South Carolina | United States | 29407 |
| 66 | Investigational Site Number 840117 | Greenville | South Carolina | United States | 29607 |
| 67 | Investigational Site Number 840021 | Spartanburg | South Carolina | United States | 29303 |
| 68 | Investigational Site Number 840062 | Amarillo | Texas | United States | 79106 |
| 69 | Investigational Site Number 840038 | Boerne | Texas | United States | 78006 |
| 70 | Investigational Site Number 840124 | Cypress | Texas | United States | 77429 |
| 71 | Investigational Site Number 840023 | Dallas | Texas | United States | 75231 |
| 72 | Investigational Site Number 840923 | El Paso | Texas | United States | 79903 |
| 73 | Investigational Site Number 840922 | Fort Worth | Texas | United States | 76109 |
| 74 | Investigational Site Number 840027 | Fort Worth | Texas | United States | 76244 |
| 75 | Investigational Site Number 840070 | McKinney | Texas | United States | 75069 |
| 76 | Investigational Site Number 840118 | Plano | Texas | United States | 75093 |
| 77 | Investigational Site Number 840008 | San Antonio | Texas | United States | 78229 |
| 78 | Investigational Site Number 840035 | Draper | Utah | United States | 84020 |
| 79 | Investigational Site Number 840077 | Murray | Utah | United States | 84107 |
| 80 | Investigational Site Number 840057 | South Burlington | Vermont | United States | 05403 |
| 81 | Investigational Site Number 840059 | Fairfax | Virginia | United States | 22030 |
| 82 | Investigational Site Number 840951 | Bellingham | Washington | United States | 98225 |
| 83 | Investigational Site Number 032096 | Bahia Blanca | Argentina | B8000JRB | |
| 84 | Investigational Site Number 032004 | Buenos Aires | Argentina | B6500BWQ | |
| 85 | Investigational Site Number 032003 | Buenos Aires | Argentina | C1121ABE | |
| 86 | Investigational Site Number 032011 | Caba | Argentina | 1120 | |
| 87 | Investigational Site Number 032097 | Caba | Argentina | C1414AIF | |
| 88 | Investigational Site Number 032001 | Caba | Argentina | C1425BEN | |
| 89 | Investigational Site Number 032010 | Caba | Argentina | C1425FVH | |
| 90 | Investigational Site Number 032091 | Caba | Argentina | C1426ABP | |
| 91 | Investigational Site Number 032095 | Capital Federal | Argentina | C1425DUC | |
| 92 | Investigational Site Number 032002 | La Plata | Argentina | B1900BNN | |
| 93 | Investigational Site Number 032006 | Rosario | Argentina | S2000BRH | |
| 94 | Investigational Site Number 032007 | Rosario | Argentina | S2000DBS | |
| 95 | Investigational Site Number 032005 | Rosario | Argentina | S2000JKR | |
| 96 | Investigational Site Number 032012 | San Miguel De Tucuman | Argentina | T4000CHE | |
| 97 | Investigational Site Number 032009 | San Miguel De Tucumán | Argentina | T4000IAR | |
| 98 | Investigational Site Number 036004 | Adelaide | Australia | 5000 | |
| 99 | Investigational Site Number 036005 | Campbelltown | Australia | 2560 | |
| 100 | Investigational Site Number 036001 | Clayton | Australia | 3168 | |
| 101 | Investigational Site Number 036008 | Frankston | Australia | 3199 | |
| 102 | Investigational Site Number 036093 | Murdoch | Australia | 6150 | |
| 103 | Investigational Site Number 036003 | Nedlands | Australia | 6009 | |
| 104 | Investigational Site Number 036094 | Parkville | Australia | 3050 | |
| 105 | Investigational Site Number 036009 | Prahran | Australia | 3004 | |
| 106 | Investigational Site Number 036006 | Woolloongabba | Australia | 4102 | |
| 107 | Investigational Site Number 056002 | Brussels | Belgium | 1020 | |
| 108 | Investigational Site Number 056003 | Gent | Belgium | 9000 | |
| 109 | Investigational Site Number 056001 | Leuven | Belgium | 3000 | |
| 110 | Investigational Site Number 076009 | Florianópolis | Brazil | 88040-970 | |
| 111 | Investigational Site Number 076007 | Porto Alegre | Brazil | 90020-090 | |
| 112 | Investigational Site Number 076001 | Porto Alegre | Brazil | 90610-000 | |
| 113 | Investigational Site Number 076003 | Salvador | Brazil | 41940-455 | |
| 114 | Investigational Site Number 076012 | Sao Paulo | Brazil | 04266-010 | |
| 115 | Investigational Site Number 076002 | Sorocaba | Brazil | 18040-425 | |
| 116 | Investigational Site Number 076013 | São Bernardo Do Campo | Brazil | 09715-090 | |
| 117 | Investigational Site Number 076006 | São Paulo | Brazil | 05437-000 | |
| 118 | Investigational Site Number 124019 | Burlington | Canada | L7N 3V2 | |
| 119 | Investigational Site Number 124009 | Calgary | Canada | T2N 4Z6 | |
| 120 | Investigational Site Number 124016 | Hamilton | Canada | L8N 4A6 | |
| 121 | Investigational Site Number 124003 | Mississauga | Canada | L5A 3V4 | |
| 122 | Investigational Site Number 124001 | Montreal | Canada | H2X 3E4 | |
| 123 | Investigational Site Number 124012 | Montreal | Canada | H4A 3J1 | |
| 124 | Investigational Site Number 124010 | Montreal | Canada | H4J 1C5 | |
| 125 | Investigational Site Number 124013 | Ottawa | Canada | K1G 6C6 | |
| 126 | Investigational Site Number 124018 | Quebec | Canada | G1V 4G5 | |
| 127 | Investigational Site Number 124014 | Quebec | Canada | G1V 4W2 | |
| 128 | Investigational Site Number 124008 | Sherbrooke | Canada | J1H 5N4 | |
| 129 | Investigational Site Number 124015 | Toronto | Canada | M5G 1E2 | |
| 130 | Investigational Site Number 124002 | Toronto | Canada | M5T 3A9 | |
| 131 | Investigational Site Number 124007 | Trois-Rivieres | Canada | G8T 7A1 | |
| 132 | Investigational Site Number 124006 | Vancouver | Canada | V5Z 1M9 | |
| 133 | Investigational Site Number 124017 | Vancouver | Canada | V6Z 1Y6 | |
| 134 | Investigational Site Number 152007 | Quillota | Chile | 2260877 | |
| 135 | Investigational Site Number 152024 | Santiago | Chile | 7500588 | |
| 136 | Investigational Site Number 152005 | Santiago | Chile | 7500692 | |
| 137 | Investigational Site Number 152014 | Santiago | Chile | 7500698 | |
| 138 | Investigational Site Number 152011 | Santiago | Chile | 7500710 | |
| 139 | Investigational Site Number 152018 | Santiago | Chile | 8207257 | |
| 140 | Investigational Site Number 152002 | Santiago | Chile | 8380456 | |
| 141 | Investigational Site Number 152013 | Santiago | Chile | 8910131 | |
| 142 | Investigational Site Number 152023 | Talcahuano | Chile | ||
| 143 | Investigational Site Number 152008 | Talca | Chile | 3460001 | |
| 144 | Investigational Site Number 152004 | Talca | Chile | ||
| 145 | Investigational Site Number 152010 | Valdivia | Chile | 5090145 | |
| 146 | Investigational Site Number 152003 | Viña Del Mar | Chile | 2520024 | |
| 147 | Investigational Site Number 152021 | Viña Del Mar | Chile | 2520594 | |
| 148 | Investigational Site Number 170001 | Bogota | Colombia | 110121 | |
| 149 | Investigational Site Number 170002 | Bogotá | Colombia | 110231 | |
| 150 | Investigational Site Number 208002 | Hvidovre | Denmark | 2650 | |
| 151 | Investigational Site Number 208001 | København Nv | Denmark | 2400 | |
| 152 | Investigational Site Number 250009 | Brest | France | 29609 | |
| 153 | Investigational Site Number 250004 | La Tronche | France | 38700 | |
| 154 | Investigational Site Number 250010 | Lille Cedex | France | 59037 | |
| 155 | Investigational Site Number 250013 | Lille Cedex | France | 59037 | |
| 156 | Investigational Site Number 250006 | Lyon | France | 69317 | |
| 157 | Investigational Site Number 250001 | Marseille | France | 13015 | |
| 158 | Investigational Site Number 250002 | Montpellier | France | 34295 | |
| 159 | Investigational Site Number 250005 | Nantes | France | 44033 | |
| 160 | Investigational Site Number 250007 | Nimes Cedex 9 | France | 30029 | |
| 161 | Investigational Site Number 250008 | Strasbourg | France | 67091 | |
| 162 | Investigational Site Number 250014 | Vandoeuvre-Les-Nancy Cedex | France | 54511 | |
| 163 | Investigational Site Number 276006 | Berlin | Germany | 10787 | |
| 164 | Investigational Site Number 276003 | Bochum | Germany | 44789 | |
| 165 | Investigational Site Number 276010 | Frankfurt Am Main | Germany | 60596 | |
| 166 | Investigational Site Number 276011 | Großhansdorf | Germany | 22927 | |
| 167 | Investigational Site Number 276009 | Koblenz | Germany | 56068 | |
| 168 | Investigational Site Number 276005 | Rüdersdorf Bei Berlin | Germany | 15562 | |
| 169 | Investigational Site Number 348301 | Balassagyarmat | Hungary | 2660 | |
| 170 | Investigational Site Number 348303 | Edelény | Hungary | 3780 | |
| 171 | Investigational Site Number 348003 | Gödöllö | Hungary | 2100 | |
| 172 | Investigational Site Number 376003 | Haifa | Israel | 34362 | |
| 173 | Investigational Site Number 376001 | Kfar Saba | Israel | 44281 | |
| 174 | Investigational Site Number 376005 | Petah-Tikva | Israel | 49100 | |
| 175 | Investigational Site Number 376002 | Rehovot | Israel | 76100 | |
| 176 | Investigational Site Number 380010 | Ancona | Italy | 60126 | |
| 177 | Investigational Site Number 380009 | Catania | Italy | 95123 | |
| 178 | Investigational Site Number 380004 | Ferrara | Italy | 44124 | |
| 179 | Investigational Site Number 380008 | Foggia | Italy | 71100 | |
| 180 | Investigational Site Number 380002 | Genova | Italy | 16132 | |
| 181 | Investigational Site Number 380003 | Modena | Italy | 41124 | |
| 182 | Investigational Site Number 380007 | Padova | Italy | 35128 | |
| 183 | Investigational Site Number 380099 | Palermo | Italy | 90146 | |
| 184 | Investigational Site Number 380001 | Pisa | Italy | 56100 | |
| 185 | Investigational Site Number 392185 | Akashi-Shi | Japan | ||
| 186 | Investigational Site Number 392009 | Asahi-Shi | Japan | ||
| 187 | Investigational Site Number 392037 | Chiyoda-Ku | Japan | ||
| 188 | Investigational Site Number 392002 | Chuo-Ku | Japan | ||
| 189 | Investigational Site Number 392007 | Chuo-Ku | Japan | ||
| 190 | Investigational Site Number 392112 | Chuo-Ku | Japan | ||
| 191 | Investigational Site Number 392012 | Edogawa-Ku | Japan | ||
| 192 | Investigational Site Number 392137 | Fukuoka-Shi | Japan | ||
| 193 | Investigational Site Number 392021 | Fukuyama-Shi | Japan | ||
| 194 | Investigational Site Number 392030 | Habikino-Shi | Japan | ||
| 195 | Investigational Site Number 392004 | Himeji-Shi | Japan | ||
| 196 | Investigational Site Number 392032 | Hirakata-Shi | Japan | ||
| 197 | Investigational Site Number 392108 | Hiroshima-Shi | Japan | ||
| 198 | Investigational Site Number 392158 | Hiroshima-Shi | Japan | ||
| 199 | Investigational Site Number 392013 | Iizuka-Shi | Japan | ||
| 200 | Investigational Site Number 392042 | Isesaki-Shi | Japan | ||
| 201 | Investigational Site Number 392023 | Kanazawa-Shi | Japan | ||
| 202 | Investigational Site Number 392142 | Kasuga-Shi | Japan | ||
| 203 | Investigational Site Number 392119 | Kishiwada-Shi | Japan | ||
| 204 | Investigational Site Number 392025 | Kobe-Shi | Japan | ||
| 205 | Investigational Site Number 392162 | Kobe-Shi | Japan | ||
| 206 | Investigational Site Number 392040 | Kodaira-Shi | Japan | ||
| 207 | Investigational Site Number 392044 | Kokubunji-Shi | Japan | ||
| 208 | Investigational Site Number 392131 | Koushi-Shi | Japan | ||
| 209 | Investigational Site Number 392010 | Kurashiki-Shi | Japan | ||
| 210 | Investigational Site Number 392036 | Kyoto-Shi | Japan | ||
| 211 | Investigational Site Number 392153 | Kyoto-Shi | Japan | ||
| 212 | Investigational Site Number 392133 | Machida-Shi | Japan | ||
| 213 | Investigational Site Number 392135 | Matsuyama-Shi | Japan | ||
| 214 | Investigational Site Number 392122 | Minato-Ku | Japan | ||
| 215 | Investigational Site Number 392144 | Minato-Ku | Japan | ||
| 216 | Investigational Site Number 392106 | Mizunami-Shi | Japan | ||
| 217 | Investigational Site Number 392164 | Muroran-Shi | Japan | ||
| 218 | Investigational Site Number 392163 | Nagoya-Shi | Japan | ||
| 219 | Investigational Site Number 392020 | Naka-Gun | Japan | ||
| 220 | Investigational Site Number 392005 | Naruto-Shi | Japan | ||
| 221 | Investigational Site Number 392187 | Obihiro-Shi | Japan | ||
| 222 | Investigational Site Number 392177 | Ome-Shi | Japan | ||
| 223 | Investigational Site Number 392152 | Osaka Sayama-Shi | Japan | ||
| 224 | Investigational Site Number 392155 | Osaka Sayama-Shi | Japan | ||
| 225 | Investigational Site Number 392170 | Osaki-Shi | Japan | ||
| 226 | Investigational Site Number 392127 | Ota-Ku | Japan | ||
| 227 | Investigational Site Number 392043 | Ota-Shi | Japan | ||
| 228 | Investigational Site Number 392169 | Sagamihara-Shi | Japan | ||
| 229 | Investigational Site Number 392024 | Sakai-Shi | Japan | ||
| 230 | Investigational Site Number 392011 | Sakaide-Shi | Japan | ||
| 231 | Investigational Site Number 392008 | Sapporo-Shi | Japan | ||
| 232 | Investigational Site Number 392034 | Sapporo-Shi | Japan | ||
| 233 | Investigational Site Number 392038 | Setagaya-Ku | Japan | ||
| 234 | Investigational Site Number 392179 | Seto-Shi | Japan | ||
| 235 | Investigational Site Number 392186 | Shibuya-Ku | Japan | ||
| 236 | Investigational Site Number 392167 | Shinagawa-Ku | Japan | ||
| 237 | Investigational Site Number 392130 | Shinjuku-Ku | Japan | ||
| 238 | Investigational Site Number 392165 | Sumida-Ku | Japan | ||
| 239 | Investigational Site Number 392146 | Tachikawa-Shi | Japan | ||
| 240 | Investigational Site Number 392173 | Tachikawa-Shi | Japan | ||
| 241 | Investigational Site Number 392006 | Tomakomai-Shi | Japan | ||
| 242 | Investigational Site Number 392029 | Tsu-Shi | Japan | ||
| 243 | Investigational Site Number 392168 | Uozu-Shi | Japan | ||
| 244 | Investigational Site Number 392132 | Urasoe-Shi | Japan | ||
| 245 | Investigational Site Number 392045 | Uruma-Shi | Japan | ||
| 246 | Investigational Site Number 392014 | Yokohama-Shi | Japan | ||
| 247 | Investigational Site Number 410002 | Bucheon-Si | Korea, Republic of | 14584 | |
| 248 | Investigational Site Number 410003 | Cheongju-Si | Korea, Republic of | 28644 | |
| 249 | Investigational Site Number 410013 | Incheon | Korea, Republic of | 21565 | |
| 250 | Investigational Site Number 410006 | Seoul | Korea, Republic of | 03080 | |
| 251 | Investigational Site Number 410008 | Seoul | Korea, Republic of | 03312 | |
| 252 | Investigational Site Number 410004 | Seoul | Korea, Republic of | 03722 | |
| 253 | Investigational Site Number 410012 | Seoul | Korea, Republic of | 04763 | |
| 254 | Investigational Site Number 410005 | Seoul | Korea, Republic of | 05505 | |
| 255 | Investigational Site Number 410007 | Seoul | Korea, Republic of | 06351 | |
| 256 | Investigational Site Number 410010 | Seoul | Korea, Republic of | 06973 | |
| 257 | Investigational Site Number 410011 | Seoul | Korea, Republic of | 08308 | |
| 258 | Investigational Site Number 410001 | Suwon | Korea, Republic of | 16499 | |
| 259 | Investigational Site Number 484013 | Chihuahua | Mexico | 31020 | |
| 260 | Investigational Site Number 484006 | Chihuahua | Mexico | 31200 | |
| 261 | Investigational Site Number 484014 | Cuautitlan Izcalli | Mexico | 54769 | |
| 262 | Investigational Site Number 484005 | Distrito Federal | Mexico | 07760 | |
| 263 | Investigational Site Number 484008 | Durango | Mexico | 34080 | |
| 264 | Investigational Site Number 484001 | Guadalajara | Mexico | 44100 | |
| 265 | Investigational Site Number 484004 | Mexico City | Mexico | 64718 | |
| 266 | Investigational Site Number 484003 | Monterrey | Mexico | 64460 | |
| 267 | Investigational Site Number 484007 | Monterrey | Mexico | 66465 | |
| 268 | Investigational Site Number 484010 | México | Mexico | 06700 | |
| 269 | Investigational Site Number 484012 | San Juan Del Rio | Mexico | 76800 | |
| 270 | Investigational Site Number 484011 | Veracruz | Mexico | 91910 | |
| 271 | Investigational Site Number 528001 | Arnhem | Netherlands | 6815 AD | |
| 272 | Investigational Site Number 528002 | Dordrecht | Netherlands | 3318 AT | |
| 273 | Investigational Site Number 616006 | Bialystok | Poland | 15-010 | |
| 274 | Investigational Site Number 616004 | Gdansk | Poland | 80-405 | |
| 275 | Investigational Site Number 616003 | Gdansk | Poland | 80-952 | |
| 276 | Investigational Site Number 616007 | Krakow | Poland | 31-159 | |
| 277 | Investigational Site Number 616097 | Krakow | Poland | 31-159 | |
| 278 | Investigational Site Number 616001 | Lodz | Poland | 90-141 | |
| 279 | Investigational Site Number 616005 | Lodz | Poland | 90-153 | |
| 280 | Investigational Site Number 616009 | Lodz | Poland | 90-329 | |
| 281 | Investigational Site Number 616096 | Poznan | Poland | 60-693 | |
| 282 | Investigational Site Number 616098 | Strzelce Opolskie | Poland | 47-100 | |
| 283 | Investigational Site Number 616008 | Warszawa | Poland | 00-013 | |
| 284 | Investigational Site Number 616010 | Warszawa | Poland | 04-141 | |
| 285 | Investigational Site Number 616011 | Znin | Poland | 88-400 | |
| 286 | Investigational Site Number 642104 | Bucharest | Romania | 011461 | |
| 287 | Investigational Site Number 642103 | Bucharest | Romania | 050159 | |
| 288 | Investigational Site Number 642102 | Cluj-Napoca | Romania | 400162 | |
| 289 | Investigational Site Number 642107 | Cluj-Napoca | Romania | 400371 | |
| 290 | Investigational Site Number 642105 | Timisoara | Romania | 300310 | |
| 291 | Investigational Site Number 642106 | Timisoara | Romania | 300310 | |
| 292 | Investigational Site Number 643013 | Ekaterinburg | Russian Federation | 620028 | |
| 293 | Investigational Site Number 643096 | Moscow | Russian Federation | 105077 | |
| 294 | Investigational Site Number 643002 | Moscow | Russian Federation | 109240 | |
| 295 | Investigational Site Number 643005 | Moscow | Russian Federation | 115280 | |
| 296 | Investigational Site Number 643007 | Moscow | Russian Federation | 117574 | |
| 297 | Investigational Site Number 643012 | Moscow | Russian Federation | 123182 | |
| 298 | Investigational Site Number 643001 | Moscow | Russian Federation | 125315 | |
| 299 | Investigational Site Number 643006 | Novosibirsk | Russian Federation | 630091 | |
| 300 | Investigational Site Number 643091 | Ryazan | Russian Federation | 390039 | |
| 301 | Investigational Site Number 643011 | Saint-Petersburg | Russian Federation | 194223 | |
| 302 | Investigational Site Number 643010 | Saint-Petersburg | Russian Federation | 194354 | |
| 303 | Investigational Site Number 643099 | St-Petersburg | Russian Federation | 193231 | |
| 304 | Investigational Site Number 643009 | St-Petersburg | Russian Federation | 197022 | |
| 305 | Investigational Site Number 643008 | Yaroslavl | Russian Federation | 150003 | |
| 306 | Investigational Site Number 710009 | Brandfort | South Africa | 9400 | |
| 307 | Investigational Site Number 710011 | Cape Town | South Africa | 7505 | |
| 308 | Investigational Site Number 710001 | Cape Town | South Africa | 7530 | |
| 309 | Investigational Site Number 710091 | Cape Town | South Africa | 7700 | |
| 310 | Investigational Site Number 710092 | Cape Town | South Africa | 7700 | |
| 311 | Investigational Site Number 710002 | Cape Town | South Africa | 7764 | |
| 312 | Investigational Site Number 710003 | Cape Town | South Africa | 8000 | |
| 313 | Investigational Site Number 710006 | Durban | South Africa | 4071 | |
| 314 | Investigational Site Number 710007 | Pretoria | South Africa | 0087 | |
| 315 | Investigational Site Number 724014 | Barcelona | Spain | 08023 | |
| 316 | Investigational Site Number 724002 | Barcelona | Spain | 08035 | |
| 317 | Investigational Site Number 724001 | Barcelona | Spain | 08036 | |
| 318 | Investigational Site Number 724010 | Palma De Mallorca | Spain | 07120 | |
| 319 | Investigational Site Number 724006 | Pozuelo De Alarcón | Spain | 28223 | |
| 320 | Investigational Site Number 724003 | Sabadell | Spain | 08208 | |
| 321 | Investigational Site Number 724007 | Sant Boi De Llobregat | Spain | 08830 | |
| 322 | Investigational Site Number 724096 | Santiago De Compostela | Spain | 15706 | |
| 323 | Investigational Site Number 724008 | Sevilla | Spain | 41071 | |
| 324 | Investigational Site Number 724097 | Valencia | Spain | 46017 | |
| 325 | Investigational Site Number 158008 | New Taipei City | Taiwan | 23561 | |
| 326 | Investigational Site Number 158007 | Taichung | Taiwan | 40447 | |
| 327 | Investigational Site Number 158009 | Taipei | Taiwan | 11031 | |
| 328 | Investigational Site Number 792002 | Ankara | Turkey | 06100 | |
| 329 | Investigational Site Number 792098 | Ankara | Turkey | 06100 | |
| 330 | Investigational Site Number 792008 | Bursa | Turkey | 16059 | |
| 331 | Investigational Site Number 792007 | Istanbul | Turkey | 34020 | |
| 332 | Investigational Site Number 792001 | Istanbul | Turkey | 34098 | |
| 333 | Investigational Site Number 792004 | Istanbul | Turkey | 34098 | |
| 334 | Investigational Site Number 792003 | Istanbul | Turkey | 34844 | |
| 335 | Investigational Site Number 792005 | Izmir | Turkey | 35040 | |
| 336 | Investigational Site Number 792090 | Izmir | Turkey | 35110 | |
| 337 | Investigational Site Number 792013 | Kirikkale | Turkey | 71450 | |
| 338 | Investigational Site Number 792006 | Mersin | Turkey | 33070 | |
| 339 | Investigational Site Number 792096 | Rize | Turkey | 53100 | |
| 340 | Investigational Site Number 804007 | Chernivtsi | Ukraine | 58001 | |
| 341 | Investigational Site Number 804023 | Dnipro | Ukraine | 49101 | |
| 342 | Investigational Site Number 804009 | Ivano-Frankivsk | Ukraine | 76018 | |
| 343 | Investigational Site Number 804094 | Ivano-Frankivsk | Ukraine | 76018 | |
| 344 | Investigational Site Number 804005 | Kharkiv | Ukraine | 61058 | |
| 345 | Investigational Site Number 804021 | Kharkiv | Ukraine | 61093 | |
| 346 | Investigational Site Number 804001 | Kharkiv | Ukraine | 61124 | |
| 347 | Investigational Site Number 804004 | Kyiv | Ukraine | 03049 | |
| 348 | Investigational Site Number 804003 | Kyiv | Ukraine | 03680 | |
| 349 | Investigational Site Number 804008 | Kyiv | Ukraine | 03680 | |
| 350 | Investigational Site Number 804017 | Kyiv | Ukraine | 03680 | |
| 351 | Investigational Site Number 804018 | Kyiv | Ukraine | 03680 | |
| 352 | Investigational Site Number 804020 | Kyiv | Ukraine | 03680 | |
| 353 | Investigational Site Number 804016 | Kyiv | Ukraine | 04050 | |
| 354 | Investigational Site Number 804006 | Odesa | Ukraine | 65025 | |
| 355 | Investigational Site Number 804002 | Poltava | Ukraine | 36038 | |
| 356 | Investigational Site Number 804014 | Ternopil | Ukraine | 46000 | |
| 357 | Investigational Site Number 804019 | Vinnytsya | Ukraine | 21001 | |
| 358 | Investigational Site Number 804015 | Yalta | Ukraine | 298603 | |
| 359 | Investigational Site Number 804022 | Zaporizhzhya | Ukraine | 69076 | |
| 360 | Investigational Site Number 804012 | Zaporizhzhya | Ukraine | 69118 | |
| 361 | Investigational Site Number 826001 | Bradford | United Kingdom | BD9 6RJ | |
| 362 | Investigational Site Number 826010 | London | United Kingdom | W2 1NY | |
| 363 | Investigational Site Number 826009 | Oxford | United Kingdom | OX3 7LE | |
| 364 | Investigational Site Number 826007 | Portsmouth | United Kingdom | PO6 3LY | |
| 365 | Investigational Site Number 826006 | South Shields | United Kingdom | NE34 0PL |
Sponsors and Collaborators
- Sanofi
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT02134028
Other Study ID Numbers:
- LTS12551
- 2013-003856-19
- U1111-1117-6745
First Posted:
May 8, 2014
Last Update Posted:
Mar 28, 2022
Last Verified:
Mar 1, 2022
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
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study was initiated at 365 sites in 27 countries. Participants who successfully completed treatment in studies DRI12544 (NCT01854047),EFC13579 (NCT02414854),EFC13691 (NCT02528214) and PDY14192 (NCT02573233) were eligible to continue their treatment in this extension study LTS12551. Total of 2282 participants were enrolled and treated in this study. |
|---|---|
| Pre-assignment Detail | The Total study duration was maximum of 108 weeks for participants enrolled prior to amendment 4 approval and a maximum of 60 weeks for participants enrolled after amendment 4. Following amendment 4 (dated 31 Oct 2016) open-label treatment duration was amended to 48 weeks (1 year); and the 16-week post-treatment period was shortened to 12 weeks. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 milligram (mg) on Day 1 followed by a subcutaneous (SC) dose of dupilumab 300 mg every 2 weeks (q2w) for 96 weeks in combination with inhaled corticosteroid (ICS) therapy/long-acting beta-agonist (LABA) therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with oral corticosteroids (OCS) and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Period Title: Overall Study | ||||||||
| STARTED | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| COMPLETED | 102 | 379 | 465 | 908 | 83 | 76 | 15 | 11 |
| NOT COMPLETED | 9 | 42 | 52 | 105 | 14 | 14 | 4 | 3 |
Baseline Characteristics
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Total of all reporting groups |
| Overall Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 | 2282 |
| Age, Customized (Count of Participants) | |||||||||
| <18 years |
0
0%
|
0
0%
|
32
6.2%
|
55
5.4%
|
1
1%
|
1
1.1%
|
0
0%
|
0
0%
|
89
3.9%
|
| 18-64 years |
101
91%
|
374
88.8%
|
422
81.6%
|
826
81.5%
|
81
83.5%
|
80
88.9%
|
19
100%
|
14
100%
|
1917
84%
|
| 65-74 years |
8
7.2%
|
40
9.5%
|
59
11.4%
|
112
11.1%
|
14
14.4%
|
8
8.9%
|
0
0%
|
0
0%
|
241
10.6%
|
| 75-84 years |
2
1.8%
|
7
1.7%
|
4
0.8%
|
20
2%
|
1
1%
|
1
1.1%
|
0
0%
|
0
0%
|
35
1.5%
|
| ≥85 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
69
62.2%
|
259
61.5%
|
335
64.8%
|
618
61%
|
57
58.8%
|
53
58.9%
|
7
36.8%
|
10
71.4%
|
1408
61.7%
|
| Male |
42
37.8%
|
162
38.5%
|
182
35.2%
|
395
39%
|
40
41.2%
|
37
41.1%
|
12
63.2%
|
4
28.6%
|
874
38.3%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
2.1%
|
0
0%
|
0
0%
|
0
0%
|
2
0.1%
|
| Asian |
18
16.2%
|
70
16.6%
|
51
9.9%
|
116
11.5%
|
1
1%
|
0
0%
|
0
0%
|
1
7.1%
|
257
11.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.2%
|
0
0%
|
1
0.1%
|
0
0%
|
1
1.1%
|
0
0%
|
0
0%
|
3
0.1%
|
| Black or African American |
1
0.9%
|
8
1.9%
|
17
3.3%
|
43
4.2%
|
1
1%
|
2
2.2%
|
2
10.5%
|
1
7.1%
|
75
3.3%
|
| White |
88
79.3%
|
339
80.5%
|
445
86.1%
|
844
83.3%
|
91
93.8%
|
86
95.6%
|
17
89.5%
|
12
85.7%
|
1922
84.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
4
3.6%
|
3
0.7%
|
4
0.8%
|
9
0.9%
|
2
2.1%
|
1
1.1%
|
0
0%
|
0
0%
|
23
1%
|
Outcome Measures
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
|---|---|
| Description | An Adverse Event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that developed, worsened, or became serious during the treatment emergent AE period (time from first dose of investigational medicinal product [IMP] in LTS12551 up to the last dose of dupilumab plus 14 weeks). A Serious AE (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. |
| Time Frame | From the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks (up to 108 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population which included participants who actually received at least 1 dose or part of a dose of the IMP in LTS12551 study. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Any TEAE |
88
79.3%
|
369
87.6%
|
414
80.1%
|
789
77.9%
|
74
76.3%
|
70
77.8%
|
18
94.7%
|
13
92.9%
|
| Any treatment emergent SAE |
14
12.6%
|
42
10%
|
48
9.3%
|
106
10.5%
|
12
12.4%
|
10
11.1%
|
0
0%
|
4
28.6%
|
| Any TEAE leading to death |
0
0%
|
3
0.7%
|
0
0%
|
1
0.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Any TEAE leading to permanent discontinuation |
3
2.7%
|
19
4.5%
|
12
2.3%
|
31
3.1%
|
4
4.1%
|
5
5.6%
|
1
5.3%
|
2
14.3%
|
| Title | Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities During the TEAE Period |
|---|---|
| Description | Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure (SBP): Less than or equal to (≤) 95 Adults (≤90 Adolescents) millimeters of mercury (mmHg) and decrease from baseline (DFB) greater than or equal to (≥) 20 mmHg; ≥ 160 Adults (≥ 119 Adolescents) mmHg and increase from baseline (IFB) ≥ 20 mmHg. Diastolic blood pressure (DBP): ≤ 45 Adults (≤54 Adolescents) mmHg and DFB ≥ 10 mmHg; ≥ 110 Adults (≥78 Adolescents) mmHg and IFB ≥ 10 mmHg. Heart rate (HR): ≤ 50 beats per minute (bpm) and DFB ≥ 20 bpm; ≥ 120 bpm and IFB ≥ 20 bpm. Respiratory rate: less than (<) 12 breaths/min(b/m); greater than (>) 20 b/m. Weight (kg): ≥ 5 percent (%) DFB; ≥ 5% IFB. Temperature: ≥ 38.0 degree Celsius (°C) rectal/ear/temporal; ≥ 37.5°C oral; ≥ 37.2°C axillary. TEAE period was defined as the time from first dose of IMP in LTS12551 up to the last dose of dupilumab plus 14 weeks. |
| Time Frame | From the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks (up to 108 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| SBP: ≤ 95 (≤90) & DFB ≥ 20 mmHg |
4
3.6%
|
12
2.9%
|
19
3.7%
|
40
3.9%
|
0
0%
|
1
1.1%
|
2
10.5%
|
0
0%
|
| SBP: ≥ 160 (≥119) & IFB ≥ 20 mmHg |
2
1.8%
|
17
4%
|
21
4.1%
|
45
4.4%
|
6
6.2%
|
1
1.1%
|
1
5.3%
|
3
21.4%
|
| DBP: ≤ 45 (≤54) & DFB ≥ 10 mmHg |
1
0.9%
|
1
0.2%
|
11
2.1%
|
15
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| DBP: ≥ 110 (≥78) & IFB ≥ 10 mmHg |
0
0%
|
4
1%
|
15
2.9%
|
20
2%
|
2
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| HR: ≤ 50 & DFB ≥ 20 bpm |
0
0%
|
3
0.7%
|
2
0.4%
|
12
1.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| HR: ≥ 120 & IFB ≥ 20 bpm |
0
0%
|
0
0%
|
2
0.4%
|
5
0.5%
|
1
1%
|
0
0%
|
0
0%
|
0
0%
|
| Respiratory rate: < 12 b/m |
5
4.5%
|
17
4%
|
18
3.5%
|
24
2.4%
|
4
4.1%
|
0
0%
|
2
10.5%
|
3
21.4%
|
| Respiratory rate: > 20 b/m |
23
20.7%
|
104
24.7%
|
88
17%
|
195
19.2%
|
18
18.6%
|
12
13.3%
|
4
21.1%
|
0
0%
|
| Weight: ≥ 5% DFB |
32
28.8%
|
106
25.2%
|
146
28.2%
|
261
25.8%
|
22
22.7%
|
29
32.2%
|
3
15.8%
|
3
21.4%
|
| Weight: ≥ 5% IFB |
45
40.5%
|
181
43%
|
189
36.6%
|
378
37.3%
|
29
29.9%
|
37
41.1%
|
8
42.1%
|
5
35.7%
|
| Temperature: ≥ 38.0°C |
0
0%
|
0
0%
|
1
0.2%
|
1
0.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Temperature: ≥ 37.5°C |
1
0.9%
|
0
0%
|
9
1.7%
|
6
0.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Temperature: ≥ 37.2°C |
3
2.7%
|
21
5%
|
4
0.8%
|
16
1.6%
|
0
0%
|
1
1.1%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters (Red Blood Cells [RBCs], Platelets and Coagulation) During the TEAE Period |
|---|---|
| Description | Criteria for potentially clinically significant abnormalities: Hemoglobin (Hb): ≤ 115 grams per liter (g/L)(Male [M]), ≤ 95 g/L (Female[ F]) (< 100 g/L Adolescents); ≥ 185 g/L (M), ≥ 165 g/L (F) (≥ 200 g/L Adolescents); DFB ≥ 20 g/L. Hematocrit: ≤ 0.37 volume/volume (v/v) (M); ≤ 0.32 v/v (F) (<0.32 v/v Adolescents); ≥ 0.55 v/v (M); 0.5 v/v (F) (>0.47 v/v Adolescents). RBCs: ≥ 6 Tera/L. Platelets: < 100 Giga(G)/L; ≥ 700 G/L. TEAE period was defined as the time from first dose of IMP in LTS12551 up to the last dose of dupilumab plus 14 weeks. |
| Time Frame | From the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks (up to 108 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Hb: ≤ 115 g/L, ≤ 95 g/L (< 100 g/L) |
2
1.8%
|
7
1.7%
|
12
2.3%
|
29
2.9%
|
0
0%
|
3
3.3%
|
0
0%
|
0
0%
|
| Hb: ≥ 185 g/L, ≥ 165 g/L(≥ 200 g/L) |
1
0.9%
|
3
0.7%
|
8
1.5%
|
4
0.4%
|
2
2.1%
|
1
1.1%
|
0
0%
|
0
0%
|
| Hb: DFB ≥ 20 g/L |
13
11.7%
|
41
9.7%
|
40
7.7%
|
118
11.6%
|
11
11.3%
|
7
7.8%
|
0
0%
|
0
0%
|
| Hematocrit: ≤ 0.37 v/v; ≤ 0.32 v/v(<0.32 v/v) |
6
5.4%
|
19
4.5%
|
23
4.4%
|
47
4.6%
|
3
3.1%
|
5
5.6%
|
0
0%
|
0
0%
|
| Hematocrit: ≥ 0.55 v/v; ≥ 0.5 v/v(>0.47 v/v) |
3
2.7%
|
6
1.4%
|
26
5%
|
36
3.6%
|
3
3.1%
|
3
3.3%
|
0
0%
|
0
0%
|
| RBCs: ≥ 6 Tera/L |
1
0.9%
|
5
1.2%
|
8
1.5%
|
15
1.5%
|
0
0%
|
2
2.2%
|
0
0%
|
1
7.1%
|
| Platelets: < 100G/ L |
0
0%
|
2
0.5%
|
2
0.4%
|
1
0.1%
|
1
1%
|
0
0%
|
0
0%
|
1
7.1%
|
| Platelets: ≥ 700 G/L |
0
0%
|
1
0.2%
|
1
0.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Severe Exacerbation Events |
|---|---|
| Description | Severe asthma exacerbation events were defined as a deterioration of asthma which required: use of systemic corticosteroids for ≥ 3 days, (participants from study EFC13691 (NCT02528214), and who were taking systemic corticosteroids: the use of systemic corticosteroids at least double the current dose and for ≥3 days.) or, hospitalization or emergency room visit because of asthma, required systemic corticosteroids. |
| Time Frame | From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Number [number of events] |
62
|
242
|
234
|
437
|
35
|
41
|
3
|
1
|
| Title | Annualized Event Rate Per Participant-Years for Severe Exacerbation |
|---|---|
| Description | The annualized event rate per participant-years was defined as the total number of events that occurred during the treatment period divided by the total number of participant-years during the treatment period. |
| Time Frame | From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Number [exacerbation per participant-years] |
0.314
|
0.330
|
0.351
|
0.331
|
0.302
|
0.391
|
0.149
|
0.077
|
| Title | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 48 and 96 |
|---|---|
| Description | FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. For this analysis, baseline was defined as respective parent study baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Week 48 |
0.24
(0.42)
|
0.28
(0.45)
|
0.34
(0.44)
|
0.36
(0.53)
|
0.31
(0.50)
|
0.33
(0.53)
|
0.23
(0.40)
|
0.01
(0.21)
|
| Week 96 |
0.22
(0.44)
|
0.27
(0.46)
|
0.33
(0.44)
|
0.31
(0.47)
|
0.36
(0.66)
|
0.25
(0.46)
|
0.14
(0.41)
|
0.01
(0.12)
|
| Title | Change From Baseline in Percent Predicted FEV1 at Weeks 48 and 96 |
|---|---|
| Description | FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. For this analysis, baseline was defined as respective parent study baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Week 48 |
9.21
(13.61)
|
10.42
(14.61)
|
11.74
(14.27)
|
12.16
(16.58)
|
10.45
(15.03)
|
12.41
(18.27)
|
5.88
(10.06)
|
1.36
(8.35)
|
| Week 96 |
8.86
(14.47)
|
10.68
(15.10)
|
12.53
(14.50)
|
11.25
(14.55)
|
13.06
(19.57)
|
10.00
(15.79)
|
4.20
(9.60)
|
2.00
(2.83)
|
| Title | Change From Baseline in Forced Vital Capacity (FVC) at Weeks 48 and 96 |
|---|---|
| Description | FVC was a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. For this analysis, baseline was defined as respective parent study baseline. |
| Time Frame | Baseline of parent study, Week 48, and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Week 48 |
0.22
(0.45)
|
0.25
(0.50)
|
0.30
(0.48)
|
0.35
(0.60)
|
0.29
(0.56)
|
0.38
(0.56)
|
0.21
(0.42)
|
0.05
(0.30)
|
| Week 96 |
0.16
(0.47)
|
0.22
(0.52)
|
0.27
(0.48)
|
0.25
(0.50)
|
0.38
(0.82)
|
0.22
(0.42)
|
0.08
(0.29)
|
0.05
(0.40)
|
| Title | Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 48 and 96 |
|---|---|
| Description | FEF was the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. For this analysis, baseline was defined as respective parent study baseline. |
| Time Frame | Baseline of parent study, Week 48, and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Week 48 |
0.27
(0.55)
|
0.31
(0.55)
|
0.39
(0.57)
|
0.39
(0.66)
|
0.34
(0.56)
|
0.29
(0.66)
|
0.23
(0.44)
|
0.04
(0.26)
|
| Week 96 |
0.28
(0.57)
|
0.32
(0.55)
|
0.38
(0.53)
|
0.36
(0.61)
|
0.42
(0.64)
|
0.27
(0.53)
|
0.19
(0.41)
|
0.04
(0.14)
|
| Title | Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Mean Scores at Weeks 24 and 48 |
|---|---|
| Description | The ACQ-5 had 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total mean score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), higher scores indicated lower asthma control. For this analysis, baseline was defined as respective parent study baseline. |
| Time Frame | Baseline of parent study, Weeks 24, and 48 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Week 24 |
-1.37
(0.91)
|
-1.48
(1.10)
|
-1.61
(1.08)
|
-1.68
(1.05)
|
-1.09
(1.10)
|
-1.15
(1.17)
|
-0.96
(1.03)
|
-0.80
(0.46)
|
| Week 48 |
-1.33
(1.07)
|
-1.57
(1.11)
|
-1.64
(1.08)
|
-1.69
(1.08)
|
-1.21
(1.00)
|
-1.06
(1.25)
|
-0.89
(1.02)
|
-0.87
(0.58)
|
| Title | Percentage of Participants Achieving ACQ-5 Score Response (ACQ-5 Responders) at Weeks 24 and 48 |
|---|---|
| Description | ACQ-5 response was defined as change from baseline in ACQ-5 scores ≥ 0.5. The ACQ-5 had 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 mean total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control. |
| Time Frame | At Weeks 24, and 48 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Week 24 |
82.7
74.5%
|
80.8
19.2%
|
84.0
16.2%
|
86.5
8.5%
|
67.7
69.8%
|
70.1
77.9%
|
57.9
304.7%
|
69.2
494.3%
|
| Week 48 |
79.0
71.2%
|
82.3
19.5%
|
85.7
16.6%
|
86.7
8.6%
|
75.6
77.9%
|
70.5
78.3%
|
60.0
315.8%
|
72.7
519.3%
|
| Title | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Scores at Weeks 24 and 48 |
|---|---|
| Description | The AQLQ was designed to measure the functional impairments that are most troublesome to adults as a result of their asthma. The AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), and environmental stimuli (4 items). Each item was scored on a 7-point likert scale ranged from 1=severely impaired to 7=not impaired. The 32 items of the questionnaire were averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired); higher scores indicated better quality of life. For this analysis, baseline was defined as respective parent study baseline. |
| Time Frame | Baseline of parent study, Weeks 24, and 48 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed for the participants from Studies DRI12544, EFC13579, and EFC13691 only. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 |
| Week 24 |
1.07
(0.99)
|
1.28
(1.24)
|
1.38
(1.15)
|
1.38
(1.16)
|
0.99
(1.10)
|
0.97
(1.26)
|
| Week 48 |
1.07
(1.13)
|
1.40
(1.19)
|
1.39
(1.17)
|
1.40
(1.18)
|
1.06
(0.98)
|
1.00
(1.23)
|
| Title | Percentage of Participants Achieving AQLQ Global Score Response (AQLQ Responders) at Weeks 24 and 48 |
|---|---|
| Description | AQLQ global response was defined as participants with change from baseline in AQLQ global score ≥ 0.5. The AQLQ was designed to measure the functional impairments that are most troublesome to adults as a result of their asthma. The AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item was scored on a 7-point likert scale (1=severely impaired, 7=not impaired). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired). Higher scores indicated better quality of life. |
| Time Frame | At Weeks 24, and 48 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed for the participants from Studies DRI12544, EFC13579, and EFC13691 only. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 |
| Week 24 |
67.6
60.9%
|
73.6
17.5%
|
77.6
15%
|
77.2
7.6%
|
64.2
66.2%
|
61.4
68.2%
|
| Week 48 |
65.0
58.6%
|
76.3
18.1%
|
77.4
15%
|
78.4
7.7%
|
73.3
75.6%
|
68.4
76%
|
| Title | Serum Concentrations of Dupilumab Over Time Till Week 96 |
|---|---|
| Description | For this analysis, baseline was defined as respective parent study baseline. Here, 'number analyzed'=number of participants with available data for each specified category. |
| Time Frame | Baseline of parent study, Weeks 0, 4, 12, 24, 48, 72, and 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Pharmacokinetics (PK) population which consisted of all the participants who had actually received at least one dose or part of a dose of dupilumab in the LTS12551 study, with at least one non-missing and evaluable pre-dose serum concentration value after the first dose of dupilumab in the LTS12551 study. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 515 | 1008 | 96 | 90 | 19 | 14 |
| Baseline |
0.00
(0.000)
|
0.00
(1990.640)
|
0.00
(2286.888)
|
0.00
(0.000)
|
0.00
(0.000)
|
|||
| Week 0 |
0.00
(0.000)
|
0.00
(0.000)
|
37230.97
(73.261)
|
40754.49
(54.858)
|
52545.41
(44.678)
|
|||
| Week 4 |
46848.70
(43.149)
|
40704.77
(47.293)
|
25847.86
(49.371)
|
50566.66
(55.104)
|
25868.25
(53.450)
|
48295.93
(52.655)
|
23336.89
(50.542)
|
56486.58
(45.755)
|
| Week 12 |
54467.13
(50.267)
|
48155.26
(52.353)
|
45406.55
(51.399)
|
55140.49
(53.114)
|
44064.95
(57.100)
|
50904.34
(51.233)
|
49026.51
(41.619)
|
55365.35
(53.317)
|
| Week 24 |
47023.84
(51.645)
|
49730.56
(53.625)
|
50984.57
(53.744)
|
54897.58
(54.044)
|
57363.72
(57.889)
|
44219.42
(55.383)
|
63080.82
(51.224)
|
60643.16
(41.617)
|
| Week 48 |
46355.26
(52.612)
|
45919.75
(55.932)
|
41867.50
(60.345)
|
41849.96
(62.049)
|
36219.47
(67.530)
|
36564.41
(60.959)
|
24864.79
(58.016)
|
53320.11
(46.714)
|
| Week 72 |
44771.52
(56.256)
|
46842.64
(53.335)
|
45628.10
(56.232)
|
46372.55
(57.719)
|
60117.76
(62.390)
|
32029.19
(66.785)
|
40362.88
(55.567)
|
26383.90
(120.013)
|
| Week 96 |
42431.08
(59.222)
|
42661.18
(59.658)
|
38908.58
(64.633)
|
39088.60
(62.897)
|
49810.65
(65.546)
|
19030.70
(67.237)
|
42360.37
(49.409)
|
56378.01
(7.140)
|
| Title | Percentage of Participants With Antidrug Antibodies (ADA) Response |
|---|---|
| Description | ADA response were categorized as: treatment emergent and treatment boosted response. 1) Treatment emergent was defined as an ADA positive response in the assay post first dose in LTS12551, when baseline results were negative or missing. 2) Treatment boosted was defined as: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive. The criteria for positive was defined as "30 to > 10,000", where low titer (< 1,000); moderate (1,000 ≤ titer ≤ 10,000) and high titer (> 10,000). |
| Time Frame | From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on ADA population which consisted of all participants who had actually received at least one dose or part of a dose of dupilumab in the LTS12551 study, with at least one pre-dose sample that was assayed successfully using the ADA assay after the first dose of dupilumab in the LTS12551 study. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 515 | 1008 | 95 | 90 | 19 | 14 |
| Treatment-emergent ADA |
10.8
9.7%
|
12.1
2.9%
|
9.5
1.8%
|
4.5
0.4%
|
7.4
7.6%
|
8.9
9.9%
|
0
0%
|
7.1
50.7%
|
| Treatment-boosted ADA |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1.1
1.1%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Change From Baseline in Blood Eosinophils Cells Count at Weeks 48 and 96 |
|---|---|
| Description | For this analysis, baseline was defined as respective parent study baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab | Participants From EFC13579: Placebo/Dupilumab | Participants From EFC13579: Dupilumab/Dupilumab | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab | Participants From PDY14192: Placebo/Dupilumab | Participants From PDY14192: Dupilumab/Dupilumab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 | 517 | 1013 | 97 | 90 | 19 | 14 |
| Week 48 |
0.007
(0.475)
|
-0.041
(0.588)
|
-0.096
(0.428)
|
-0.099
(0.360)
|
0.098
(0.450)
|
0.016
(0.382)
|
-0.066
(0.181)
|
-0.026
(0.187)
|
| Week 96 |
-0.074
(0.251)
|
-0.081
(0.562)
|
-0.161
(0.391)
|
-0.114
(0.354)
|
-0.051
(0.399)
|
0.083
(0.642)
|
-0.103
(0.039)
|
0.025
(0.134)
|
| Title | Change From Baseline in Morning Peak Expiratory Flow (PEF) at Weeks 48 and 96: Participants From Study DRI12544 |
|---|---|
| Description | The PEF was a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at morning and evening. Morning PEF was performed within 15 minutes after arising (between 5:30 AM and 10 AM) prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol. For this analysis, baseline was defined as parent study DRI12544 baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study DRI12544 and not for the participants from other studies. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 |
| Week 48 |
13.26
(76.71)
|
22.95
(70.06)
|
| Week 96 |
13.63
(83.88)
|
21.69
(77.70)
|
| Title | Change From Baseline in Evening Peak Expiratory Flow (PEF) at Weeks 48 and 96: Participants From Study DRI12544 |
|---|---|
| Description | The PEF was a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at morning and evening. Evening PEF was performed in the evening (between 5:30 PM and 10 PM) prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol. For this analysis, baseline was defined as parent DRI12544 study baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study DRI12544 and not for the participants from other studies. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 |
| Week 48 |
4.65
(75.00)
|
11.97
(72.19)
|
| Week 96 |
1.16
(79.47)
|
10.05
(79.47)
|
| Title | Change From Baseline in Morning Asthma Symptom Scores at Weeks 48 and 96: Participants From Study DRI12544 |
|---|---|
| Description | Morning asthma symptom score was determined using AM (ante meridiem) symptom scoring system which evaluated participant's overall asthma symptoms experienced during the night. It ranges from 0 to 4 as: 0=no asthma symptoms, slept through the night, 1=slept well, but some complaints in the morning. No nighttime awakenings, 2=woke up once because of asthma (including early awakening), 3=woke up several times because of asthma (including early awakening), 4=bad night, awake most of the night because of asthma; higher scores indicated more severe symptoms. For this analysis, baseline was defined as parent DRI12544 study baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study DRI12544 and not for the participants from other studies. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 |
| Week 48 |
-0.49
(0.78)
|
-0.68
(0.79)
|
| Week 96 |
-0.52
(0.90)
|
-0.76
(0.81)
|
| Title | Change From Baseline in Evening Asthma Symptom Scores at Weeks 48 and 96: Participants From Study DRI12544 |
|---|---|
| Description | Evening asthma symptom score was determined using PM (post meridiem) symptom scoring system which evaluated participant's overall asthma symptoms experienced during the day. It ranged from 0 to 4 as: 0=very well, no asthma symptoms, 1=one episode of wheezing, cough, or breathlessness, 2=more than one episode of wheezing, cough, or breathlessness without interference of normal activities, 3=wheezing, cough, or breathlessness most of the day, which interfered to some extent with normal activities, 4=asthma very bad, unable to carry out daily activities as usual; higher scores indicated more severe symptoms. For this analysis, baseline was defined as parent DRI12544 study baseline. |
| Time Frame | Baseline of parent study, Week 48, and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study DRI12544 and not for the participants from other studies. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 |
| Week 48 |
-0.47
(0.81)
|
-0.72
(0.85)
|
| Week 96 |
-0.49
(0.94)
|
-0.79
(0.88)
|
| Title | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol for Symptom Relief at Weeks 48 and 96: Participants From Study DRI12544 |
|---|---|
| Description | The number of salbutamol/albuterol or levosalbutamol/levalbuterol inhalations was recorded daily by the participants in an electronic diary/PEF meter. Mean number of inhalations in last 7 days prior to each visit was calculated and was used in computation of data reported. For this analysis, baseline was defined as parent DRI12544 study baseline. |
| Time Frame | Baseline of parent study, Week 48, and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study DRI12544 and not for the participants from other studies. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 |
| Week 48 |
-0.00
(3.65)
|
0.68
(4.80)
|
| Week 96 |
-0.14
(4.17)
|
-0.82
(5.18)
|
| Title | Change From Baseline in Number of Nocturnal Awakenings at Weeks 48 and 96: Participants From Study DRI12544 |
|---|---|
| Description | The number of nocturnal awakening because of asthma symptoms were recorded every morning by the participants in an electronic diary. Mean number of awakenings in last 7 days prior to each visit was calculated and was used in computation of data reported. For this analysis, baseline was defined as parent DRI12544 study baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study DRI12544 and not for the participants from other studies. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 |
| Week 48 |
-0.27
(0.54)
|
-0.43
(0.89)
|
| Week 96 |
-0.29
(0.58)
|
-0.49
(0.96)
|
| Title | Percent Change From Baseline in Oral Corticosteroid (OCS) Dose at Weeks 48, and 96: Participants From Study EFC13691 |
|---|---|
| Description | OCS was allowed as background controller medication for the participants from study EFC13691 only. For this analysis, baseline was defined as parent study EFC13691 baseline. |
| Time Frame | Baseline of parent study, Weeks 48 and 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study EFC13691 and not for the participants from other studies. |
| Arm/Group Title | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 97 | 90 |
| Week 48 |
55.32
(42.98)
|
80.23
(30.44)
|
| Week 96 |
71.37
(29.37)
|
88.16
(26.83)
|
| Title | Percentage of Participants Achieving a Reduction of 50% or Greater (≥ 50% ) in OCS Dose Over Time at Weeks 48 and 96: Participants From Study EFC13691 |
|---|---|
| Description | OCS was allowed as background controller medication for the participants from study EFC13691 only. Percentage of participants who achieved a reduction of ≥ 50% in OCS dose were reported. |
| Time Frame | Weeks 48 and 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study EFC13691 and not for the participants from other studies. |
| Arm/Group Title | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 97 | 90 |
| Week 48 |
64.9
58.5%
|
86.0
20.4%
|
| Week 96 |
82.1
74%
|
94.7
22.5%
|
| Title | Percentage of Participants With Background OCS Completely Tapered Off Over Time at Weeks 48 and 96: Participants From Study EFC13691 |
|---|---|
| Description | OCS was allowed as background controller medication for the participants from study EFC13691 only. Number of participants who gradually discontinued or reduced therapeutic dose were reported in this outcome measure. |
| Time Frame | Weeks 48, and 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study EFC13691 and not for the participants from other studies. |
| Arm/Group Title | Participants From EFC13691: Placebo/Dupilumab | Participants From EFC13691: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 97 | 90 |
| Week 48 |
31.2
28.1%
|
59.6
14.2%
|
| Week 96 |
42.9
38.6%
|
78.9
18.7%
|
| Title | Change From Baseline in European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Scores at Weeks 48 and 96: Participants From Study DRI12544 |
|---|---|
| Description | EQ-5D-3L: validated and reliable self-report health status questionnaire consisted of EQ-5D descriptive system and visual analogue scale (VAS). EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: no problem, some problems, and severe problems. The 5 dimensional 3-level systems was converted into single index utility score, and the score was 0 - 100, where 100=best health state; and 0=worst health state; where higher scores indicated better outcome. For this analysis, baseline was defined as parent DRI12544 study baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study DRI12544 and not for the participants from other studies. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 |
| Week 48 |
0.13
(0.20)
|
0.14
(0.21)
|
| Week 96 |
0.12
(0.18)
|
0.13
(0.21)
|
| Title | Change From Baseline in EQ-5D-3L VAS Scores at Weeks 48 and 96: Participants From Study DRI12544 |
|---|---|
| Description | EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0=worst imaginable health state and 100=best imaginable health state, where higher states indicated better outcomes. For this analysis, baseline was defined as parent DRI12544 study baseline. |
| Time Frame | Baseline of parent study, Week 48 and Week 96 of this extension study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on exposed population. Here, 'number analyzed' = number of participants with available data for each specified category. Data were planned to be collected and analyzed only for the participants from Study DRI12544 and not for the participants from other studies. |
| Arm/Group Title | Participants From DRI12544: Placebo/Dupilumab | Participants From DRI12544: Dupilumab/Dupilumab |
|---|---|---|
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. |
| Measure Participants | 111 | 421 |
| Week 48 |
10.10
(15.40)
|
12.88
(18.76)
|
| Week 96 |
9.90
(18.92)
|
13.95
(18.81)
|
Adverse Events
| Time Frame | Reported AE and deaths were TEAEs that developed, worsened, or became serious and deaths that occurred during the TEAE period (time from the first dose of dupilumab in LTS12551 up to the last dose of dupilumab plus 14 weeks) (i.e. up to 108 weeks). | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Analysis was performed on safety population. | |||||||||||||||
| Arm/Group Title | Participants From DRI12544 Study Placebo/Dupilumab | Participants From DRI12544 Study Dupilumab/Dupilumab | Participants From EFC13579 Study Placebo/Dupilumab | Participants From EFC13579 Study Dupilumab/Dupilumab | Participants From EFC13691 Study Placebo/Dupilumab | Participants From EFC13691 Study Dupilumab/Dupilumab | Participants From PDY14192 Study Placebo/Dupilumab | Participants From PDY14192 Study Dupilumab/Dupilumab | ||||||||
| Arm/Group Description | Participants who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with CS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | Participants who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | ||||||||
All Cause Mortality |
||||||||||||||||
| Participants From DRI12544 Study Placebo/Dupilumab | Participants From DRI12544 Study Dupilumab/Dupilumab | Participants From EFC13579 Study Placebo/Dupilumab | Participants From EFC13579 Study Dupilumab/Dupilumab | Participants From EFC13691 Study Placebo/Dupilumab | Participants From EFC13691 Study Dupilumab/Dupilumab | Participants From PDY14192 Study Placebo/Dupilumab | Participants From PDY14192 Study Dupilumab/Dupilumab | |||||||||
| 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 | 0/111 (0%) | 3/421 (0.7%) | 0/517 (0%) | 1/1013 (0.1%) | 0/97 (0%) | 0/90 (0%) | 0/19 (0%) | 0/14 (0%) | ||||||||
Serious Adverse Events |
||||||||||||||||
| Participants From DRI12544 Study Placebo/Dupilumab | Participants From DRI12544 Study Dupilumab/Dupilumab | Participants From EFC13579 Study Placebo/Dupilumab | Participants From EFC13579 Study Dupilumab/Dupilumab | Participants From EFC13691 Study Placebo/Dupilumab | Participants From EFC13691 Study Dupilumab/Dupilumab | Participants From PDY14192 Study Placebo/Dupilumab | Participants From PDY14192 Study Dupilumab/Dupilumab | |||||||||
| 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 | 14/111 (12.6%) | 42/421 (10%) | 48/517 (9.3%) | 106/1013 (10.5%) | 12/97 (12.4%) | 10/90 (11.1%) | 0/19 (0%) | 4/14 (28.6%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Acute Coronary Syndrome | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Acute Left Ventricular Failure | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Angina Unstable | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Aortic Valve Incompetence | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Atrial Fibrillation | 0/111 (0%) | 0 | 2/421 (0.5%) | 2 | 2/517 (0.4%) | 2 | 5/1013 (0.5%) | 10 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Atrioventricular Block Complete | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Cardiac Failure | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Myocardial Ischaemia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 3/1013 (0.3%) | 3 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Myocarditis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||||||||||||
| Odontogenic Cyst | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||
| Vertigo | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Endocrine disorders | ||||||||||||||||
| Goitre | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Eye disorders | ||||||||||||||||
| Angle Closure Glaucoma | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Cataract | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Serous Retinal Detachment | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal Hernia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Abdominal Incarcerated Hernia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Abdominal Pain | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Abdominal Pain Upper | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Diaphragmatic Hernia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Diverticulum Intestinal | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Gastritis | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Gastritis Erosive | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Gastroenteritis Eosinophilic | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Hiatus Hernia | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Inguinal Hernia | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Intestinal Obstruction | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Intra-Abdominal Haemorrhage | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Large Intestine Polyp | 0/111 (0%) | 0 | 2/421 (0.5%) | 2 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Oesophageal Food Impaction | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pancreatitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Retroperitoneum Cyst | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Tooth Impacted | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Umbilical Hernia | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Upper Gastrointestinal Haemorrhage | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Vomiting | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| General disorders | ||||||||||||||||
| Adverse Drug Reaction | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Injection Site Erythema | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||
| Cholecystitis Acute | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Cholelithiasis | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 4/1013 (0.4%) | 4 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Hepatomegaly | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Immune system disorders | ||||||||||||||||
| Anaphylactic Reaction | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Drug Hypersensitivity | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Eosinophilic Granulomatosis With Polyangiitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 2/1013 (0.2%) | 2 | 1/97 (1%) | 1 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Hypersensitivity | 0/111 (0%) | 0 | 1/421 (0.2%) | 2 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Infections and infestations | ||||||||||||||||
| Abscess Limb | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Appendicitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Bronchitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Bronchopulmonary Aspergillosis Allergic | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Cellulitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Cervicitis | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Chronic Sinusitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Diverticulitis | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Ear Infection | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Gastroenteritis | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Herpes Simplex Encephalitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Influenza | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Large Intestine Infection | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Lower Respiratory Tract Infection | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Lower Respiratory Tract Infection Bacterial | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Mycobacterium Avium Complex Infection | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pneumonia | 3/111 (2.7%) | 3 | 4/421 (1%) | 4 | 4/517 (0.8%) | 4 | 7/1013 (0.7%) | 7 | 1/97 (1%) | 1 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pneumonia Bacterial | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Post Procedural Infection | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pyelonephritis Acute | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Salmonellosis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Sialoadenitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Sinusitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Tonsillitis | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Wound Infection | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| Ankle Fracture | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Chemical Peritonitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Craniocerebral Injury | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Facial Bones Fracture | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Fall | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Forearm Fracture | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Hand Fracture | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Head Injury | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Incision Site Pain | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Incisional Hernia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Lower Limb Fracture | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Lumbar Vertebral Fracture | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Meniscus Injury | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Post Procedural Complication | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Post Procedural Constipation | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pulmonary Contusion | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Radius Fracture | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Skin Laceration | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Upper Limb Fracture | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Investigations | ||||||||||||||||
| Alanine Aminotransferase Increased | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Dehydration | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Diabetes Mellitus | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Diabetic Metabolic Decompensation | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Intervertebral Disc Protrusion | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Osteoarthritis | 0/111 (0%) | 0 | 3/421 (0.7%) | 4 | 1/517 (0.2%) | 1 | 4/1013 (0.4%) | 4 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Osteonecrosis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pain In Extremity | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Rotator Cuff Syndrome | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Adenocarcinoma Gastric | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Adenocarcinoma Of Colon | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Basal Cell Carcinoma | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 3/1013 (0.3%) | 3 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Benign Ovarian Tumour | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Bowen's Disease | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Breast Cancer | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 2/517 (0.4%) | 2 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Colon Adenoma | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Colon Cancer | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Endometrial Cancer | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Fibroadenoma Of Breast | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Follicular Thyroid Cancer | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Gastric Adenoma | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Hodgkin's Disease | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Intraductal Proliferative Breast Lesion | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Juvenile Melanoma Benign | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Large Intestine Benign Neoplasm | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Lung Cancer Metastatic | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Metastases To Central Nervous System | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Non-Small Cell Lung Cancer | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Osteochondroma | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Ovarian Cancer | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Papillary Thyroid Cancer | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 3/1013 (0.3%) | 3 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Prostate Cancer | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Prostate Cancer Stage I | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Rectal Cancer | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Squamous Cell Carcinoma Of Skin | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Uterine Leiomyoma | 0/111 (0%) | 0 | 3/421 (0.7%) | 3 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||
| Carotid Artery Disease | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Cerebral Infarction | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Cerebrovascular Accident | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Dizziness | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Dyskinesia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Headache | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Hypertensive Cerebrovascular Disease | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Idiopathic Intracranial Hypertension | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Neuritis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Optic Neuritis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Paraesthesia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Parkinson's Disease | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Seizure | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Syncope | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Thalamic Infarction | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Transient Ischaemic Attack | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||
| Abortion Spontaneous | 0/111 (0%) | 0 | 2/421 (0.5%) | 2 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Pregnancy | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||
| Delirium | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Depressed Mood | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Depression | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Suicide Attempt | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||
| Acute Kidney Injury | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Iga Nephropathy | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Ureterolithiasis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Urinary Incontinence | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||
| Adenomyosis | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Benign Prostatic Hyperplasia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Endometrial Hyperplasia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Haemorrhagic Ovarian Cyst | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Ovarian Cyst | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Vaginal Prolapse | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Acute Respiratory Failure | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Asthma | 4/111 (3.6%) | 4 | 2/421 (0.5%) | 2 | 13/517 (2.5%) | 13 | 18/1013 (1.8%) | 19 | 0/97 (0%) | 0 | 5/90 (5.6%) | 5 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Atelectasis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Nasal Septum Deviation | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Nasal Septum Perforation | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pleural Effusion | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pneumothorax | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pulmonary Embolism | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pulmonary Oedema | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Respiratory Failure | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Sinusitis Noninfective | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Status Asthmaticus | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Vocal Cord Polyp | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Erythema Nodosum | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Rash Erythematous | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Rash Vesicular | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Social circumstances | ||||||||||||||||
| Miscarriage Of Partner | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Vascular disorders | ||||||||||||||||
| Aortic Dilatation | 0/111 (0%) | 0 | 1/421 (0.2%) | 3 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Deep Vein Thrombosis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Hypertensive Crisis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| Participants From DRI12544 Study Placebo/Dupilumab | Participants From DRI12544 Study Dupilumab/Dupilumab | Participants From EFC13579 Study Placebo/Dupilumab | Participants From EFC13579 Study Dupilumab/Dupilumab | Participants From EFC13691 Study Placebo/Dupilumab | Participants From EFC13691 Study Dupilumab/Dupilumab | Participants From PDY14192 Study Placebo/Dupilumab | Participants From PDY14192 Study Dupilumab/Dupilumab | |||||||||
| 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 | 80/111 (72.1%) | 323/421 (76.7%) | 357/517 (69.1%) | 666/1013 (65.7%) | 56/97 (57.7%) | 55/90 (61.1%) | 18/19 (94.7%) | 13/14 (92.9%) | ||||||||
| Ear and labyrinth disorders | ||||||||||||||||
| Ear Pain | 0/111 (0%) | 0 | 2/421 (0.5%) | 2 | 1/517 (0.2%) | 1 | 6/1013 (0.6%) | 6 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Tinnitus | 0/111 (0%) | 0 | 2/421 (0.5%) | 2 | 3/517 (0.6%) | 3 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Eye disorders | ||||||||||||||||
| Dry Eye | 0/111 (0%) | 0 | 4/421 (1%) | 5 | 2/517 (0.4%) | 2 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal Distension | 0/111 (0%) | 0 | 2/421 (0.5%) | 2 | 1/517 (0.2%) | 1 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Abdominal Pain | 3/111 (2.7%) | 3 | 12/421 (2.9%) | 13 | 9/517 (1.7%) | 11 | 13/1013 (1.3%) | 16 | 4/97 (4.1%) | 4 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Abdominal Pain Upper | 0/111 (0%) | 0 | 5/421 (1.2%) | 5 | 6/517 (1.2%) | 6 | 10/1013 (1%) | 11 | 1/97 (1%) | 1 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Dental Caries | 1/111 (0.9%) | 2 | 6/421 (1.4%) | 6 | 4/517 (0.8%) | 4 | 9/1013 (0.9%) | 9 | 1/97 (1%) | 1 | 1/90 (1.1%) | 1 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Diarrhoea | 3/111 (2.7%) | 3 | 16/421 (3.8%) | 20 | 7/517 (1.4%) | 9 | 25/1013 (2.5%) | 27 | 4/97 (4.1%) | 4 | 3/90 (3.3%) | 3 | 2/19 (10.5%) | 2 | 2/14 (14.3%) | 2 |
| Dyspepsia | 1/111 (0.9%) | 1 | 1/421 (0.2%) | 2 | 1/517 (0.2%) | 1 | 7/1013 (0.7%) | 8 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Gastrointestinal Disorder | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Gastrooesophageal Reflux Disease | 1/111 (0.9%) | 1 | 13/421 (3.1%) | 14 | 13/517 (2.5%) | 15 | 21/1013 (2.1%) | 23 | 2/97 (2.1%) | 2 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Haemorrhoidal Haemorrhage | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Nausea | 2/111 (1.8%) | 2 | 6/421 (1.4%) | 36 | 8/517 (1.5%) | 8 | 14/1013 (1.4%) | 52 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 3/19 (15.8%) | 4 | 1/14 (7.1%) | 1 |
| Oesophagitis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Vomiting | 2/111 (1.8%) | 2 | 4/421 (1%) | 4 | 5/517 (1%) | 5 | 13/1013 (1.3%) | 15 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 4/19 (21.1%) | 5 | 0/14 (0%) | 0 |
| General disorders | ||||||||||||||||
| Fatigue | 1/111 (0.9%) | 1 | 10/421 (2.4%) | 12 | 5/517 (1%) | 5 | 8/1013 (0.8%) | 15 | 5/97 (5.2%) | 5 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Injection Site Bruising | 0/111 (0%) | 0 | 1/421 (0.2%) | 2 | 1/517 (0.2%) | 1 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Injection Site Erythema | 26/111 (23.4%) | 102 | 55/421 (13.1%) | 412 | 35/517 (6.8%) | 148 | 50/1013 (4.9%) | 295 | 5/97 (5.2%) | 12 | 2/90 (2.2%) | 29 | 8/19 (42.1%) | 21 | 6/14 (42.9%) | 29 |
| Injection Site Haematoma | 4/111 (3.6%) | 4 | 2/421 (0.5%) | 2 | 4/517 (0.8%) | 4 | 4/1013 (0.4%) | 7 | 1/97 (1%) | 3 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 2/14 (14.3%) | 2 |
| Injection Site Haemorrhage | 5/111 (4.5%) | 7 | 5/421 (1.2%) | 5 | 5/517 (1%) | 5 | 2/1013 (0.2%) | 4 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 2/19 (10.5%) | 2 | 0/14 (0%) | 0 |
| Injection Site Oedema | 4/111 (3.6%) | 9 | 14/421 (3.3%) | 84 | 14/517 (2.7%) | 32 | 15/1013 (1.5%) | 58 | 0/97 (0%) | 0 | 2/90 (2.2%) | 8 | 3/19 (15.8%) | 6 | 2/14 (14.3%) | 4 |
| Injection Site Pain | 9/111 (8.1%) | 18 | 18/421 (4.3%) | 28 | 15/517 (2.9%) | 40 | 14/1013 (1.4%) | 51 | 0/97 (0%) | 0 | 2/90 (2.2%) | 9 | 1/19 (5.3%) | 3 | 2/14 (14.3%) | 2 |
| Injection Site Pruritus | 12/111 (10.8%) | 23 | 16/421 (3.8%) | 54 | 15/517 (2.9%) | 36 | 7/1013 (0.7%) | 20 | 2/97 (2.1%) | 2 | 0/90 (0%) | 0 | 2/19 (10.5%) | 3 | 0/14 (0%) | 0 |
| Injection Site Reaction | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 3/517 (0.6%) | 3 | 5/1013 (0.5%) | 10 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Injection Site Warmth | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 20 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Malaise | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Peripheral Swelling | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 3/517 (0.6%) | 3 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Pyrexia | 1/111 (0.9%) | 1 | 8/421 (1.9%) | 12 | 0/517 (0%) | 0 | 16/1013 (1.6%) | 20 | 1/97 (1%) | 1 | 3/90 (3.3%) | 4 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Immune system disorders | ||||||||||||||||
| Drug Hypersensitivity | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 4/1013 (0.4%) | 4 | 2/97 (2.1%) | 2 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Multiple Allergies | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Infections and infestations | ||||||||||||||||
| Bronchitis | 15/111 (13.5%) | 30 | 80/421 (19%) | 135 | 63/517 (12.2%) | 100 | 117/1013 (11.5%) | 181 | 9/97 (9.3%) | 10 | 14/90 (15.6%) | 15 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Bronchitis Viral | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 4/1013 (0.4%) | 4 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Conjunctivitis | 0/111 (0%) | 0 | 5/421 (1.2%) | 5 | 5/517 (1%) | 5 | 18/1013 (1.8%) | 21 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Gastroenteritis | 6/111 (5.4%) | 6 | 7/421 (1.7%) | 8 | 10/517 (1.9%) | 14 | 26/1013 (2.6%) | 31 | 0/97 (0%) | 0 | 2/90 (2.2%) | 2 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Genital Herpes | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 2 | 0/14 (0%) | 0 |
| Gingivitis | 1/111 (0.9%) | 1 | 3/421 (0.7%) | 3 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Infection | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Influenza | 5/111 (4.5%) | 5 | 44/421 (10.5%) | 52 | 30/517 (5.8%) | 39 | 67/1013 (6.6%) | 79 | 9/97 (9.3%) | 11 | 7/90 (7.8%) | 10 | 2/19 (10.5%) | 2 | 2/14 (14.3%) | 2 |
| Lower Respiratory Tract Infection | 1/111 (0.9%) | 2 | 6/421 (1.4%) | 6 | 6/517 (1.2%) | 7 | 17/1013 (1.7%) | 18 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Nasopharyngitis | 27/111 (24.3%) | 47 | 109/421 (25.9%) | 208 | 99/517 (19.1%) | 149 | 191/1013 (18.9%) | 293 | 17/97 (17.5%) | 30 | 16/90 (17.8%) | 22 | 3/19 (15.8%) | 8 | 6/14 (42.9%) | 8 |
| Oral Candidiasis | 1/111 (0.9%) | 5 | 9/421 (2.1%) | 19 | 6/517 (1.2%) | 9 | 14/1013 (1.4%) | 19 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 1/19 (5.3%) | 2 | 0/14 (0%) | 0 |
| Pharyngitis | 16/111 (14.4%) | 21 | 37/421 (8.8%) | 57 | 26/517 (5%) | 30 | 59/1013 (5.8%) | 75 | 1/97 (1%) | 1 | 4/90 (4.4%) | 5 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
| Pharyngitis Streptococcal | 0/111 (0%) | 0 | 1/421 (0.2%) | 2 | 6/517 (1.2%) | 6 | 7/1013 (0.7%) | 7 | 1/97 (1%) | 1 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Post Procedural Infection | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Postoperative Wound Infection | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Pulpitis Dental | 1/111 (0.9%) | 1 | 2/421 (0.5%) | 2 | 0/517 (0%) | 0 | 5/1013 (0.5%) | 6 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 2 | 0/14 (0%) | 0 |
| Respiratory Tract Infection | 3/111 (2.7%) | 3 | 15/421 (3.6%) | 17 | 5/517 (1%) | 6 | 18/1013 (1.8%) | 25 | 0/97 (0%) | 0 | 2/90 (2.2%) | 2 | 2/19 (10.5%) | 2 | 0/14 (0%) | 0 |
| Respiratory Tract Infection Viral | 0/111 (0%) | 0 | 3/421 (0.7%) | 6 | 6/517 (1.2%) | 7 | 11/1013 (1.1%) | 15 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Rhinitis | 7/111 (6.3%) | 8 | 11/421 (2.6%) | 11 | 6/517 (1.2%) | 7 | 22/1013 (2.2%) | 25 | 4/97 (4.1%) | 4 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Sinusitis | 9/111 (8.1%) | 16 | 33/421 (7.8%) | 56 | 32/517 (6.2%) | 43 | 50/1013 (4.9%) | 66 | 2/97 (2.1%) | 2 | 4/90 (4.4%) | 4 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Upper Respiratory Tract Infection | 18/111 (16.2%) | 30 | 60/421 (14.3%) | 87 | 65/517 (12.6%) | 96 | 130/1013 (12.8%) | 213 | 8/97 (8.2%) | 12 | 6/90 (6.7%) | 15 | 2/19 (10.5%) | 4 | 0/14 (0%) | 0 |
| Urinary Tract Infection | 5/111 (4.5%) | 7 | 26/421 (6.2%) | 31 | 17/517 (3.3%) | 20 | 42/1013 (4.1%) | 53 | 4/97 (4.1%) | 4 | 3/90 (3.3%) | 3 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Viral Upper Respiratory Tract Infection | 2/111 (1.8%) | 3 | 11/421 (2.6%) | 15 | 13/517 (2.5%) | 16 | 30/1013 (3%) | 48 | 1/97 (1%) | 4 | 1/90 (1.1%) | 3 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| Accidental Overdose | 6/111 (5.4%) | 9 | 40/421 (9.5%) | 44 | 28/517 (5.4%) | 31 | 45/1013 (4.4%) | 48 | 5/97 (5.2%) | 5 | 5/90 (5.6%) | 6 | 2/19 (10.5%) | 2 | 0/14 (0%) | 0 |
| Arthropod Bite | 2/111 (1.8%) | 2 | 4/421 (1%) | 5 | 3/517 (0.6%) | 3 | 9/1013 (0.9%) | 9 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Concussion | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 1/14 (7.1%) | 1 |
| Contusion | 3/111 (2.7%) | 3 | 14/421 (3.3%) | 27 | 12/517 (2.3%) | 13 | 14/1013 (1.4%) | 18 | 0/97 (0%) | 0 | 2/90 (2.2%) | 3 | 0/19 (0%) | 0 | 3/14 (21.4%) | 3 |
| Fall | 2/111 (1.8%) | 2 | 7/421 (1.7%) | 8 | 12/517 (2.3%) | 12 | 33/1013 (3.3%) | 38 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 2/19 (10.5%) | 2 | 0/14 (0%) | 0 |
| Intentional Overdose | 1/111 (0.9%) | 1 | 3/421 (0.7%) | 3 | 0/517 (0%) | 0 | 2/1013 (0.2%) | 2 | 2/97 (2.1%) | 2 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Limb Injury | 1/111 (0.9%) | 1 | 1/421 (0.2%) | 2 | 3/517 (0.6%) | 3 | 3/1013 (0.3%) | 4 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 2/14 (14.3%) | 2 |
| Lip Injury | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Muscle Strain | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 7/1013 (0.7%) | 7 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Skin Laceration | 1/111 (0.9%) | 1 | 5/421 (1.2%) | 5 | 10/517 (1.9%) | 10 | 7/1013 (0.7%) | 7 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Stab Wound | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Tooth Fracture | 3/111 (2.7%) | 3 | 1/421 (0.2%) | 1 | 1/517 (0.2%) | 1 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Wrist Fracture | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 2/517 (0.4%) | 2 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Investigations | ||||||||||||||||
| Blood Glucose Increased | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| C-Reactive Protein Increased | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Epstein-Barr Virus Test Positive | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| White Blood Cells Urine Positive | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 2 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Dehydration | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 9/111 (8.1%) | 10 | 23/421 (5.5%) | 29 | 23/517 (4.4%) | 29 | 22/1013 (2.2%) | 22 | 7/97 (7.2%) | 7 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 2/14 (14.3%) | 2 |
| Back Pain | 4/111 (3.6%) | 4 | 30/421 (7.1%) | 33 | 23/517 (4.4%) | 28 | 52/1013 (5.1%) | 67 | 5/97 (5.2%) | 5 | 0/90 (0%) | 0 | 2/19 (10.5%) | 2 | 3/14 (21.4%) | 4 |
| Bursitis | 1/111 (0.9%) | 2 | 2/421 (0.5%) | 2 | 2/517 (0.4%) | 2 | 1/1013 (0.1%) | 1 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Intervertebral Disc Protrusion | 0/111 (0%) | 0 | 6/421 (1.4%) | 6 | 3/517 (0.6%) | 3 | 3/1013 (0.3%) | 3 | 1/97 (1%) | 2 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Muscle Spasms | 1/111 (0.9%) | 2 | 4/421 (1%) | 6 | 7/517 (1.4%) | 9 | 9/1013 (0.9%) | 10 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 1/14 (7.1%) | 1 |
| Myalgia | 5/111 (4.5%) | 5 | 14/421 (3.3%) | 14 | 7/517 (1.4%) | 7 | 12/1013 (1.2%) | 14 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 2/19 (10.5%) | 2 | 0/14 (0%) | 0 |
| Myositis | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 2/517 (0.4%) | 2 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Pain In Extremity | 2/111 (1.8%) | 2 | 6/421 (1.4%) | 6 | 7/517 (1.4%) | 8 | 16/1013 (1.6%) | 16 | 1/97 (1%) | 1 | 3/90 (3.3%) | 3 | 1/19 (5.3%) | 1 | 1/14 (7.1%) | 1 |
| Rotator Cuff Syndrome | 1/111 (0.9%) | 1 | 1/421 (0.2%) | 1 | 1/517 (0.2%) | 1 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Tendonitis | 2/111 (1.8%) | 3 | 4/421 (1%) | 4 | 0/517 (0%) | 0 | 5/1013 (0.5%) | 5 | 1/97 (1%) | 1 | 2/90 (2.2%) | 2 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Trismus | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Pituitary Tumour Benign | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||
| Carpal Tunnel Syndrome | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 3/1013 (0.3%) | 3 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Dizziness | 3/111 (2.7%) | 3 | 12/421 (2.9%) | 13 | 8/517 (1.5%) | 8 | 6/1013 (0.6%) | 7 | 2/97 (2.1%) | 2 | 0/90 (0%) | 0 | 2/19 (10.5%) | 3 | 0/14 (0%) | 0 |
| Dysaesthesia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Headache | 13/111 (11.7%) | 14 | 47/421 (11.2%) | 141 | 47/517 (9.1%) | 69 | 74/1013 (7.3%) | 145 | 4/97 (4.1%) | 4 | 5/90 (5.6%) | 5 | 4/19 (21.1%) | 9 | 1/14 (7.1%) | 1 |
| Migraine | 2/111 (1.8%) | 2 | 3/421 (0.7%) | 3 | 7/517 (1.4%) | 14 | 9/1013 (0.9%) | 9 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 2/14 (14.3%) | 2 |
| Paraesthesia | 1/111 (0.9%) | 1 | 3/421 (0.7%) | 3 | 1/517 (0.2%) | 1 | 4/1013 (0.4%) | 4 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Presyncope | 0/111 (0%) | 0 | 2/421 (0.5%) | 2 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Somnolence | 1/111 (0.9%) | 1 | 4/421 (1%) | 6 | 1/517 (0.2%) | 1 | 1/1013 (0.1%) | 1 | 2/97 (2.1%) | 2 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Syncope | 1/111 (0.9%) | 1 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 2/1013 (0.2%) | 2 | 0/97 (0%) | 0 | 1/90 (1.1%) | 3 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||
| Anxiety | 1/111 (0.9%) | 1 | 1/421 (0.2%) | 1 | 7/517 (1.4%) | 7 | 10/1013 (1%) | 11 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Insomnia | 2/111 (1.8%) | 3 | 6/421 (1.4%) | 7 | 6/517 (1.2%) | 6 | 8/1013 (0.8%) | 8 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Sleep Disorder | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Renal and urinary disorders | ||||||||||||||||
| Leukocyturia | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Urinary Retention | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Reproductive system and breast disorders | ||||||||||||||||
| Endometriosis | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Metrorrhagia | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Cough | 4/111 (3.6%) | 4 | 16/421 (3.8%) | 24 | 10/517 (1.9%) | 12 | 22/1013 (2.2%) | 29 | 3/97 (3.1%) | 3 | 3/90 (3.3%) | 4 | 3/19 (15.8%) | 3 | 0/14 (0%) | 0 |
| Dyspnoea | 2/111 (1.8%) | 2 | 10/421 (2.4%) | 11 | 8/517 (1.5%) | 8 | 12/1013 (1.2%) | 23 | 2/97 (2.1%) | 7 | 2/90 (2.2%) | 3 | 2/19 (10.5%) | 2 | 1/14 (7.1%) | 1 |
| Nasal Congestion | 1/111 (0.9%) | 1 | 5/421 (1.2%) | 5 | 3/517 (0.6%) | 3 | 5/1013 (0.5%) | 5 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Oropharyngeal Pain | 3/111 (2.7%) | 5 | 13/421 (3.1%) | 13 | 11/517 (2.1%) | 11 | 20/1013 (2%) | 22 | 2/97 (2.1%) | 2 | 5/90 (5.6%) | 5 | 1/19 (5.3%) | 1 | 1/14 (7.1%) | 1 |
| Paranasal Sinus Discomfort | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 2/19 (10.5%) | 2 | 0/14 (0%) | 0 |
| Sinus Congestion | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 2/517 (0.4%) | 3 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 1/90 (1.1%) | 1 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Sputum Increased | 1/111 (0.9%) | 1 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Upper Respiratory Tract Congestion | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Wheezing | 1/111 (0.9%) | 1 | 0/421 (0%) | 0 | 3/517 (0.6%) | 5 | 3/1013 (0.3%) | 4 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Dermatitis Atopic | 0/111 (0%) | 0 | 2/421 (0.5%) | 5 | 5/517 (1%) | 5 | 9/1013 (0.9%) | 11 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Dyshidrotic Eczema | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 1/1013 (0.1%) | 1 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Papulopustular Rosacea | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Pityriasis Alba | 0/111 (0%) | 0 | 0/421 (0%) | 0 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Rash Generalised | 1/111 (0.9%) | 1 | 1/421 (0.2%) | 1 | 1/517 (0.2%) | 1 | 0/1013 (0%) | 0 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 1/19 (5.3%) | 1 | 0/14 (0%) | 0 |
| Rosacea | 0/111 (0%) | 0 | 1/421 (0.2%) | 1 | 1/517 (0.2%) | 1 | 3/1013 (0.3%) | 3 | 0/97 (0%) | 0 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Solar Dermatitis | 1/111 (0.9%) | 1 | 1/421 (0.2%) | 1 | 0/517 (0%) | 0 | 0/1013 (0%) | 0 | 1/97 (1%) | 1 | 0/90 (0%) | 0 | 0/19 (0%) | 0 | 1/14 (7.1%) | 1 |
| Vascular disorders | ||||||||||||||||
| Hypertension | 5/111 (4.5%) | 5 | 16/421 (3.8%) | 19 | 19/517 (3.7%) | 20 | 29/1013 (2.9%) | 37 | 5/97 (5.2%) | 7 | 2/90 (2.2%) | 2 | 0/19 (0%) | 0 | 0/14 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | 800-633-1610 ext 1# |
| Contact-US@sanofi.com |
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT02134028
Other Study ID Numbers:
- LTS12551
- 2013-003856-19
- U1111-1117-6745
First Posted:
May 8, 2014
Last Update Posted:
Mar 28, 2022
Last Verified:
Mar 1, 2022