Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Reslizumab in Patients With Eosinophilic Asthma (NCT NCT01285323)

Last Updated: 2021-11-09

Results Overview

An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization. CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

464 participants

Primary outcome timeframe

Day 1 to Month 12

Results posted on

2021-11-09

Participant Flow

A total of 1111 patients were screened for this study. Of the 1111 patients screened, 464 patients at 82 centers in 15 countries were randomly assigned to double-blind treatment.

Participant milestones

Participant milestones
Measure	Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Overall Study STARTED	232	232
Overall Study Full Analysis Set	232	232
Overall Study Safety Analysis Set	232	232
Overall Study COMPLETED	199	202
Overall Study NOT COMPLETED	33	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Overall Study Adverse Event	9	8
Overall Study Lack of Efficacy	4	2
Overall Study Withdrawal by Subject	15	11
Overall Study Protocol Violation	1	2
Overall Study Non-compliance with study procedures	2	3
Overall Study Lost to Follow-up	1	1
Overall Study Other	1	3

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Reslizumab in Patients With Eosinophilic Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=232 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=232 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Total n=464 Participants Total of all reporting groups
Age, Continuous	47.5 years STANDARD_DEVIATION 13.75 • n=5 Participants	46.4 years STANDARD_DEVIATION 13.79 • n=7 Participants	47.0 years STANDARD_DEVIATION 13.76 • n=5 Participants
Sex: Female, Male Female	150 Participants n=5 Participants	144 Participants n=7 Participants	294 Participants n=5 Participants
Sex: Female, Male Male	82 Participants n=5 Participants	88 Participants n=7 Participants	170 Participants n=5 Participants
Race White	169 participants n=5 Participants	168 participants n=7 Participants	337 participants n=5 Participants
Race Black	4 participants n=5 Participants	6 participants n=7 Participants	10 participants n=5 Participants
Race Asian	21 participants n=5 Participants	16 participants n=7 Participants	37 participants n=5 Participants
Race American Indian or Alaskan Native	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants
Race Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race Other	33 participants n=5 Participants	35 participants n=7 Participants	68 participants n=5 Participants
Weight	73.9 kg STANDARD_DEVIATION 15.93 • n=5 Participants	74.7 kg STANDARD_DEVIATION 15.72 • n=7 Participants	74.3 kg STANDARD_DEVIATION 15.81 • n=5 Participants
Height	165.2 cm STANDARD_DEVIATION 9.81 • n=5 Participants	166.4 cm STANDARD_DEVIATION 9.56 • n=7 Participants	165.8 cm STANDARD_DEVIATION 9.69 • n=5 Participants
Body Mass Index	27 kg/m^2 STANDARD_DEVIATION 5.05 • n=5 Participants	27 kg/m^2 STANDARD_DEVIATION 5.26 • n=7 Participants	27 kg/m^2 STANDARD_DEVIATION 5.15 • n=5 Participants
Oral Corticosteroid Use at Baseline Yes	27 participants n=5 Participants	27 participants n=7 Participants	54 participants n=5 Participants
Oral Corticosteroid Use at Baseline No	205 participants n=5 Participants	205 participants n=7 Participants	410 participants n=5 Participants
Participants in the United States Yes	15 participants n=5 Participants	16 participants n=7 Participants	31 participants n=5 Participants
Participants in the United States No	217 participants n=5 Participants	216 participants n=7 Participants	433 participants n=5 Participants
Asthma exacerbations in the previous 12 months	2.0 exacerbations STANDARD_DEVIATION 1.78 • n=5 Participants	1.9 exacerbations STANDARD_DEVIATION 1.58 • n=7 Participants	1.9 exacerbations STANDARD_DEVIATION 1.68 • n=5 Participants
Forced Expiratory Volume in 1 Second (FEV1)	2.004 liters STANDARD_DEVIATION 0.6682 • n=5 Participants	2.129 liters STANDARD_DEVIATION 0.7848 • n=7 Participants	2.066 liters STANDARD_DEVIATION 0.7307 • n=5 Participants
Asthma Control Questionnaire (ACQ)	2.605 units on a scale STANDARD_DEVIATION 0.79 • n=5 Participants	2.570 units on a scale STANDARD_DEVIATION 0.89 • n=7 Participants	2.587 units on a scale STANDARD_DEVIATION 0.84 • n=5 Participants
Asthma Quality of Life Questionnaire (AQLQ)	4.223 units on a scale STANDARD_DEVIATION 1.0794 • n=5 Participants	4.352 units on a scale STANDARD_DEVIATION 1.0220 • n=7 Participants	4.287 units on a scale STANDARD_DEVIATION 1.0521 • n=5 Participants
Asthma Symptom Utility Index (ASUI)	0.649 units on a scale STANDARD_DEVIATION 0.1919 • n=5 Participants	0.664 units on a scale STANDARD_DEVIATION 0.2005 • n=7 Participants	0.656 units on a scale STANDARD_DEVIATION 0.1961 • n=5 Participants
Blood Eosinophil Count	0.688 10^9 blood eosinophil/L STANDARD_DEVIATION 0.6824 • n=5 Participants	0.610 10^9 blood eosinophil/L STANDARD_DEVIATION 0.4115 • n=7 Participants	0.649 10^9 blood eosinophil/L STANDARD_DEVIATION 0.5642 • n=5 Participants
Number of Short-Acting Beta-Agonist Puffs (SABA) Daily	2.7 puffs/day STANDARD_DEVIATION 2.41 • n=5 Participants	2.9 puffs/day STANDARD_DEVIATION 2.82 • n=7 Participants	2.8 puffs/day STANDARD_DEVIATION 2.62 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Month 12

Population: Randomized set includes all patients who were randomly assigned to a treatment group at enrollment, regardless of whether or not a patient took any study drug.

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=232 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment	2.115 CAEs in 52 weeks Interval 1.329 to 3.365	0.859 CAEs in 52 weeks Interval 0.549 to 1.345

PRIMARY outcome

Timeframe: Day 1 to Month 12

Population: Randomized set includes all patients who were randomly assigned to a treatment group at enrollment, regardless of whether or not a patient took any study drug.

An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals for the two criteria were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means.

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=232 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) Requiring systemic corticosterioids >3 days	1.660 CAEs in 52 weeks Interval 1.005 to 2.744	0.646 CAEs in 52 weeks Interval 0.397 to 1.053
Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) Requiring hospitalization or ER visit	0.047 CAEs in 52 weeks Interval 0.013 to 0.168	0.033 CAEs in 52 weeks Interval 0.009 to 0.12

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Week 16

Population: Randomized set includes all patients who were randomly assigned to a treatment group at enrollment, regardless of whether or not a patient took any study drug. Number analyzed reflects participants with both baseline and Week 16 assessments.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=214 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) At Week 16	0.122 liters Standard Error 0.0447	0.223 liters Standard Error 0.0445

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16

Population: Randomized set includes all patients who were randomly assigned to a treatment group at enrollment, regardless of whether or not a patient took any study drug. Includes participants who contributed at least once to the analysis.

FEV1 is a standard measurement of air movement in the lungs of patients with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer. During study (Weeks 4, 8, 12 and 16) average value used a mixed effect model for repeated measures (MMRM) with treatment group, visit, treatment and visit interaction, and stratification factors as fixed effects and participant as a random effect. Covariates for baseline values were also included in the model; for pulmonary function test analyses, covariates for height and sex were included as well. Positive change from baseline scores indicate improvement in asthma control.

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=230 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures	0.094 liters Standard Error 0.041	0.187 liters Standard Error 0.041

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Week 16

Population: Randomized set of participants with assessments at each timepoint.

The AQLQ is a 32-item instrument administered as a self-assessment (Juniper et al 1992). The questionnaire is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (1=severe impairment, 7=no impairment). The overall AQLQ score is the mean of all 32 responses. Five of the activity questions were "patient-specific," which means that each patient identified and scored 5 activities in which the patient was limited by asthma; these 5 activities were identified at the first visit and retained for all subsequent follow-up visits. Positive change from baseline scores indicate improvement in quality of life.

Outcome measures

Outcome measures
Measure	Placebo n=216 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=213 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16	0.777 units on a scale Standard Error 0.1152	0.987 units on a scale Standard Error 0.1158

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16

Population: Randomized set, including participants who contributed at least once to the analysis.

The ACQ is a 7-item instrument that measures asthma control (Juniper et al 1999). Six questions are self-assessments; the seventh item, completed by a member of the study staff, is the result of the patient's FEV1 measurement. Each item has 7 possible answers on a scale of 0 to 6, and the total score is the mean of all responses (the total scale is therefore 0-6). A higher score is an indication of poorer asthma control. The during treatment (Weeks 4, 8, 12 and 16) average ACQ was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Negative change from baseline scores indicate improvement in asthma control.

Outcome measures

Outcome measures
Measure	Placebo n=228 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=230 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures	-0.660 units on a scale Standard Error 0.0875	-0.857 units on a scale Standard Error 0.0872

SECONDARY outcome

Timeframe: Day 1 to Day 526 (longest treatment time plus 2 weeks)

Population: Randomized set

An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization. CAEs were adjudicated by committee to assure consistency. The distributions were compared by a log rank test stratified by baseline usage of oral corticosteroid (yes or no) and geographical region (US or other).

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=232 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)	NA weeks Insufficient data to estimate time	NA weeks Insufficient data to estimate time

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16

Population: Randomized set, including participants who contributed at least once to the analysis.

The ASUI is an 11-item instrument designed to assess the frequency and severity of asthma symptoms and side effects, weighted by patient preferences (Revicki et al 1998). ASUI is a utility score that ranges from 0 to 1, with higher values indicating better asthma control; info obtained from questionnaire about asthma symptoms. The during treatment (Weeks 4, 8, 12 and 16) average ASUI was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Positive change from baseline values indicate improvement in asthma symptoms. Information was obtained from questionnaire about asthma symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=224 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=227 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures	0.080 units on a scale Standard Error 0.0161	0.115 units on a scale Standard Error 0.0161

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16

Population: Randomized set including patients who contributed at least once to the analysis.

SABA are used for quick relief of asthma symptoms. To measure SABA use, at each clinical visit patients were asked to recall their usage of SABA therapy within the last 3 days of the scheduled visit. If usage was confirmed, the number of puffs used was recorded. For the purpose of summaries, an average daily usage was evaluated by dividing the total number of puffs recorded over 3 days by 3. The during treatment (Weeks 4, 8, 12 and 16) average SABA use was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Negative change from baseline scores indicate improvement in asthma control.

Outcome measures

Outcome measures
Measure	Placebo n=188 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=180 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures	-0.44 SABA puffs per day Standard Error 0.233	-0.50 SABA puffs per day Standard Error 0.230

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 or early withdrawal

Population: Randomized set including patients who contributed at least once to the analysis.

The blood eosinophil counts were measured using a standard complete blood count (CBC) with differential blood test. Results of all differential blood tests conducted after randomization were blinded. The during treatment average eosinophil count was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. The 'over 16 weeks' value used data from Weeks 4, 8, 12 and 16. The 'over 52 weeks' value used all the during study time points listed in the Time Frame field. Negative change from baseline values correlate to reduced asthma severity.

Outcome measures

Outcome measures
Measure	Placebo n=226 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=230 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures Over 52 weeks	-0.076 10^9 blood eosinophil/L Standard Error 0.0233	-0.565 10^9 blood eosinophil/L Standard Error 0.0231
Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures Over first 16 weeks	-0.076 10^9 blood eosinophil/L Standard Error 0.0268	-0.555 10^9 blood eosinophil/L Standard Error 0.0266

SECONDARY outcome

Timeframe: Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.

Population: Safety analysis set

An adverse event (AE) was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=232 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Participants With Treatment-Emergent Adverse Events TEAE) Any TEAE	201 participants	177 participants
Participants With Treatment-Emergent Adverse Events TEAE) Mild TEAE	36 participants	67 participants
Participants With Treatment-Emergent Adverse Events TEAE) Moderate TEAE	140 participants	98 participants
Participants With Treatment-Emergent Adverse Events TEAE) Treatment-related AE	27 participants	34 participants
Participants With Treatment-Emergent Adverse Events TEAE) Deaths	0 participants	0 participants
Participants With Treatment-Emergent Adverse Events TEAE) Severe TEAE	25 participants	12 participants
Participants With Treatment-Emergent Adverse Events TEAE) Mild treatment-related AE	14 participants	22 participants
Participants With Treatment-Emergent Adverse Events TEAE) Moderate treatment-related AE	13 participants	11 participants
Participants With Treatment-Emergent Adverse Events TEAE) Severe treatment-related AE	0 participants	1 participants
Participants With Treatment-Emergent Adverse Events TEAE) TEAE causing patient discontinuation	9 participants	8 participants
Participants With Treatment-Emergent Adverse Events TEAE) Serious AEs	23 participants	18 participants

SECONDARY outcome

Timeframe: Week 4 to Week 52

Population: Safety analysis set, including participants who contributed to the analysis

Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology (except for eosinophil values), and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Creatinine: \>=177 μmol/L * Urate: M\>=625, F\>=506 μmol/L * Aspartate aminotransferase (AST): \>=3\*upper limit of normal (ULN) * Alanine aminotransferase (ALT): \>=3\*ULN * GGT = gamma-glutamyl transpeptidase: \>= 3\*ULN * Total bilirubin: \>=34.2 μmol/L * White blood cells (low): \<=3.0\*10\^9/L * White blood cells (high): \>=20\*10\^9/L * Hemoglobin (age \>=18 years): M\<=115, F\<=95 g/dL * Hematocrit (age \>=18 years): M\<0.37, F\<0.32 L/L * Eosinophils/leukocytes: \>=10.0% * Platelets: \<=75\*10\^9/L * Neutrophils: \<=1.0\*10\^9/L * Urinalysis: blood, ketones, glucose, and protein: \>=2 unit increase from baseline

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=230 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Blood urea nitrogen	5 participants	4 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Creatinine	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urate	5 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values GGT	11 participants	9 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Leukocytes (low)	3 participants	10 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Leukocytes (high)	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Hemoglobin	5 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Hematocrit	10 participants	8 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Eosinophils/leukocytes	168 participants	10 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values AST	3 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values ALT	7 participants	3 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Bilirubin	3 participants	3 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Platelets	1 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Neutrophils	14 participants	9 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urine blood (hemoglobin)	28 participants	12 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urine ketones	6 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urine glucose	9 participants	7 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urine protein	28 participants	28 participants

SECONDARY outcome

Timeframe: Week 4 to Week 52

Population: Safety analysis set including participants who contributed data to the analysis

Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Sitting pulse (high): \>100 and increase of \>= 30 beats/minute * Sitting systolic blood pressure (low): \<90 and decrease of \>= 30 mmHg * Sitting systolic blood pressure (high): \>160 and increase of \>= 30 mmHg * Sitting diastolic blood pressure (low): \<50 and decrease of \>=12 mmHg (if 12-17 years old: \<55 and decrease of \>=12 mmHg 0 * Sitting diastolic blood pressure (high): \>100 and increase of \>=12 mmHg * Respiratory rate (low): \<6 breaths/minute * Respiratory rate (high): \>24 and increase of \>=10 breaths/minute * Body temperature (low): \<35.8° Celsius * Body temperature (high): \>=38.1 and increase of \>=1.1° Celsius

Outcome measures

Outcome measures
Measure	Placebo n=230 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=230 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting pulse (high)	6 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting systolic blood pressure (low)	2 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Body temperature (high)	1 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values >=1 postbaseline vital sign abnormality	58 participants	49 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting systolic blood pressure (high)	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting diastolic blood pressure (low)	4 participants	3 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting diastolic blood pressure (high)	3 participants	4 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Respiratory rate (low)	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Respiratory rate (high)	4 participants	5 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Body temperature (low)	50 participants	39 participants

SECONDARY outcome

Timeframe: Baseline visit (prior to reslizumab exposure), Weeks 16, 32, 48 and 52

Population: Safety analysis set

Counts of participants with a positive anti-drug antibody (ADA) response during treatment is offered for the experimental treatment arm. Blood samples were collected for determination of ADAs before study drug infusion.

Outcome measures

Outcome measures
Measure	Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=232 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Participants With a Positive Anti-Reslizumab Antibody Status During Study Baseline	—	10 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Week 16	—	10 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Week 32	—	10 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Week 48	—	10 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Week 52	—	10 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study >=1 positive test result	—	15 participants

Adverse Events

Placebo

Serious events: 23 serious events

Other events: 160 other events

Deaths: 0 deaths

Reslizumab 3.0 mg/kg

Serious events: 18 serious events

Other events: 123 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=232 participants at risk Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=232 participants at risk Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Infections and infestations Bronchitis	6.0% 14/232 • Number of events 15 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.86% 2/232 • Number of events 5 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Nasopharyngitis	24.1% 56/232 • Number of events 88 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	19.4% 45/232 • Number of events 71 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Upper respiratory tract infection	6.9% 16/232 • Number of events 27 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	3.4% 8/232 • Number of events 16 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Musculoskeletal and connective tissue disorders Back pain	3.4% 8/232 • Number of events 8 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	5.2% 12/232 • Number of events 13 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Nervous system disorders Headache	6.9% 16/232 • Number of events 20 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	14.2% 33/232 • Number of events 55 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Asthma	50.9% 118/232 • Number of events 293 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	28.4% 66/232 • Number of events 133 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 215-591-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=232 participants at risk Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=232 participants at risk Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Cardiac disorders Extrasystoles	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Cardiac disorders Ventricular tachycardia	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Gastrointestinal disorders Duodenal ulcer	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Gastrointestinal disorders Inguinal hernia	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Immune system disorders Anaphylactic reaction	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.86% 2/232 • Number of events 2 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Bronchitis bacterial	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Cellulitis	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Diverticulitis	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Erysipelas	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Liver abscess	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Localised infection	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Mycobacterium fortuitum infection	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Pneumonia	2.6% 6/232 • Number of events 6 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.86% 2/232 • Number of events 2 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Pyelonephritis	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Sinusitis	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Tracheobronchitis	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Infections and infestations Urinary tract infection	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Brachial plexus injury	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Contusion	0.86% 2/232 • Number of events 2 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Fall	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Head injury	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Laceration	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Meniscus lesion	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Post concussion syndrome	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Radius fracture	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Road traffic accident	1.3% 3/232 • Number of events 3 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Spinal column injury	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Injury, poisoning and procedural complications Tendon rupture	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Nervous system disorders Carotid artery stenosis	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Nervous system disorders Dizziness	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Nervous system disorders Headache	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Nervous system disorders Migraine	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Nervous system disorders Syncope	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Allergic sinusitis	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Asthma	2.6% 6/232 • Number of events 7 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	1.3% 3/232 • Number of events 3 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Asthmatic crisis	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Bronchial secretion retention	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.43% 1/232 • Number of events 1 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.	0.00% 0/232 • Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.