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Study of Fluticasone Propionate MDPI Compared With Fluticasone/Salmeterol MDPI in Adolescent and Adult Patients With Persistent Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02139644
Recruitment Status : Completed
First Posted : May 15, 2014
Results First Posted : April 12, 2017
Last Update Posted : April 12, 2017
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: FS MDPI
Drug: Fp MDPI
Drug: Placebo MDPI
Drug: albuterol/salbutamol
Drug: Beclomethasone dipropionate
Enrollment 787
Recruitment Details A total of 1363 patients with persistent asthma were screened for enrollment into this study. 787 patients at 129 investigational centers in the US and elsewhere internationally met entry criteria and were considered eligible for enrollment into the study.
Pre-assignment Details Patients were randomized 1:1:1:1:1 to one of the five treatment arms during the Treatment Period.
Arm/Group Title Enrolled Patients FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description During the run-in period (from the screening visit to the randomization visit), all patients replaced their current rescue medication with study-specific rescue medication (albuterol/salbutamol HFA MDI) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the period. All patients discontinued their current ICS or ICS/LABA, and took 1 inhalation twice a day from a single-blinded placebo MDPI device and 1 puff twice a day from open-label QVAR 40 mcg HFA MDI (or equivalent).

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Period Title: Run-In Period (Pre-assignment)
Started 787 [1] 0 0 0 0 0
Completed 647 0 0 0 0 0
Not Completed 140 0 0 0 0 0
Reason Not Completed
Randomization criteria not met             70             0             0             0             0             0
Inclusion criteria not met             30             0             0             0             0             0
Withdrawal by Subject             12             0             0             0             0             0
Exclusion criteria met             11             0             0             0             0             0
Lost to Follow-up             8             0             0             0             0             0
Adverse Event             3             0             0             0             0             0
Not specified             6             0             0             0             0             0
[1]
Enrolled
Period Title: Treatment Period
Started 0 129 [1] 129 [1] 130 [1] 129 [1] 130 [1]
Completed 0 126 121 121 121 113
Not Completed 0 3 8 9 8 17
Reason Not Completed
Adverse Event             0             0             3             2             1             6
Withdrawal by Subject             0             0             2             2             3             2
Non-compliance             0             0             0             1             0             0
Protocol Violation             0             0             0             1             1             1
Disease progression             0             0             0             1             1             2
Lost to Follow-up             0             0             1             1             1             1
Lack of Efficacy             0             0             1             0             1             4
Not specified             0             3             1             1             0             1
[1]
Randomized
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI Total
Hide Arm/Group Description

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Total of all reporting groups
Overall Number of Baseline Participants 129 129 130 129 130 647
Hide Baseline Analysis Population Description
Intent to treat population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
41.0  (17.00) 41.4  (18.61) 40.6  (17.16) 43.3  (17.96) 40.9  (17.35) 41.5  (17.60)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
Adolescents (12-17 years)
19
  14.7%
19
  14.7%
18
  13.8%
13
  10.1%
17
  13.1%
86
  13.3%
Adults (18-64 years)
100
  77.5%
97
  75.2%
102
  78.5%
93
  72.1%
102
  78.5%
494
  76.4%
Adults (65+ years)
10
   7.8%
13
  10.1%
10
   7.7%
23
  17.8%
11
   8.5%
67
  10.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
Female
72
  55.8%
71
  55.0%
76
  58.5%
75
  58.1%
70
  53.8%
364
  56.3%
Male
57
  44.2%
58
  45.0%
54
  41.5%
54
  41.9%
60
  46.2%
283
  43.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
White
105
  81.4%
109
  84.5%
93
  71.5%
107
  82.9%
101
  77.7%
515
  79.6%
Black or African American
20
  15.5%
19
  14.7%
30
  23.1%
18
  14.0%
26
  20.0%
113
  17.5%
Asian
4
   3.1%
1
   0.8%
4
   3.1%
1
   0.8%
1
   0.8%
11
   1.7%
American Indian or Alaskan Native
0
   0.0%
0
   0.0%
1
   0.8%
0
   0.0%
0
   0.0%
1
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.8%
0
   0.0%
1
   0.2%
Other
0
   0.0%
0
   0.0%
2
   1.5%
2
   1.6%
2
   1.5%
6
   0.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
Not Hispanic or Latino
119
  92.2%
121
  93.8%
114
  87.7%
121
  93.8%
122
  93.8%
597
  92.3%
Hispanic or Latino
10
   7.8%
8
   6.2%
16
  12.3%
8
   6.2%
7
   5.4%
49
   7.6%
Unknown
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.8%
1
   0.2%
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
27.94  (6.686) 28.00  (7.166) 27.63  (6.603) 27.94  (7.259) 27.99  (6.849) 27.90  (6.897)
History of Smoking  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
Prior smoker
18
  14.0%
13
  10.1%
15
  11.5%
14
  10.9%
12
   9.2%
72
  11.1%
No tobacco use
111
  86.0%
116
  89.9%
115
  88.5%
115
  89.1%
118
  90.8%
575
  88.9%
Previous Asthma Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
Inhaled corticosteroid
97
  75.2%
90
  69.8%
83
  63.8%
89
  69.0%
102
  78.5%
461
  71.3%
Inhaled corticosteroid/long-acting beta2-agonist
32
  24.8%
39
  30.2%
47
  36.2%
40
  31.0%
28
  21.5%
186
  28.7%
Forced Expiratory Volume in 1 second (FEV1)   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters
Number Analyzed 129 participants 129 participants 130 participants 129 participants 130 participants 647 participants
2.162  (0.5522) 2.302  (0.6526) 2.166  (0.5725) 2.134  (0.6362) 2.188  (0.5628) 2.190  (0.5977)
[1]
Measure Description: participants with valid measurements (n=126, 128, 129, 129, 129)
1.Primary Outcome
Title Standardized Baseline-Adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Effect Curve From Time Zero to 12 Hours Postdose (FEV1 AUEC0-12h) at Week 12
Hide Description

A subset of approximately 300 patients who performed postdose serial spirometry is based on sample size calculation. Data from these assessments were used to analyze the primary endpoint of baseline adjusted FEV1 AUEC0-12h at week 12 using the trapezoidal rule based on actual time of measurement. It was standardized by dividing it by the number of hours between the start time of dose administration and the end time of the last nonmissing FEV1 measurement.

The baseline FEV1 was the average of the 2 predose FEV1 measurements (30 and 10 minutes predose). If 1 of these was missing, the nonmissing value was used; if both were missing, baseline was treated as missing. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting the baseline FEV1 value.

Time Frame Day 1 (predose, baseline), Week 12 and was performed at the following times relative to the administration of study drug (±5 minutes): 15 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, and 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: a subset of patients who performed postdose serial spirometry at the baseline visit and week 12
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 61 56 72 63 60
Least Squares Mean (Standard Error)
Unit of Measure: liters
0.408  (0.0465) 0.399  (0.0479) 0.254  (0.0434) 0.268  (0.0457) 0.074  (0.0487)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 100 mcg
Comments A fixed-sequence multiple testing procedure was used to control the overall Type I error rate at the 0.05 level (2-sided) for the primary endpoints analyses. Analyses appear in the defined sequence. This is the first in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0076
Comments [Not Specified]
Method ANCOVA
Comments Fixed effects of treatment, sex, (pooled) center, previous therapy (ICS or ICS/LABA), and covariates of age and baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.154
Confidence Interval (2-Sided) 95%
0.041 to 0.267
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 50 mcg
Comments A fixed-sequence multiple testing procedure was used to control the overall Type I error rate at the 0.05 level (2-sided) for the primary endpoints analyses. Analyses appear in the defined sequence. This is the second in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0322
Comments [Not Specified]
Method ANCOVA
Comments Fixed effects of treatment, sex, (pooled) center, previous therapy (ICS or ICS/LABA), and covariates of age and baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.131
Confidence Interval (2-Sided) 95%
0.011 to 0.250
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Placebo MDPI
Comments A fixed-sequence multiple testing procedure was used to control the overall Type I error rate at the 0.05 level (2-sided) for the primary endpoints analyses. Analyses appear in the defined sequence. This is the third in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments [Not Specified]
Method ANCOVA
Comments Fixed effects of treatment, sex, (pooled) center, previous therapy (ICS or ICS/LABA), and covariates of age and baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.335
Confidence Interval (2-Sided) 95%
0.216 to 0.453
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Placebo MDPI
Comments A fixed-sequence multiple testing procedure was used to control the overall Type I error rate at the 0.05 level (2-sided) for the primary endpoints analyses. Analyses appear in the defined sequence. This is the fourth in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments [Not Specified]
Method ANCOVA
Comments Fixed effects of treatment, sex, (pooled) center, previous therapy (ICS or ICS/LABA), and covariates of age and baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.325
Confidence Interval (2-Sided) 95%
0.203 to 0.447
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
Hide Description

Trough FEV1 was a morning spirometry taken predose and pre-rescue bronchodilator. If the patient inadvertently administered asthma medication/study drug at home on the AM of the visit, or if the patient took rescue medication within 6 hours of testing, the visit was rescheduled.

The baseline for predose FEV1 was defined as the average of the 30-minute and 10-minute predose measurements obtained at the randomization visit (Day 1).

Time Frame Day 1 (predose, baseline), Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 126 128 129 128 129
Least Squares Mean (Standard Error)
Unit of Measure: liters
0.315  (0.0352) 0.319  (0.0350) 0.204  (0.0340) 0.172  (0.0347) 0.053  (0.0350)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Placebo MDPI
Comments A fixed-sequence multiple testing procedure was used to control the overall Type I error rate at the 0.05 level (2-sided) for the primary endpoints analyses. Analyses appear in the defined sequence. This is the fifth in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments [Not Specified]
Method ANCOVA
Comments Effects due to baseline trough AM FEV1, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.262
Confidence Interval (2-Sided) 95%
0.168 to 0.356
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Placebo MDPI
Comments A fixed-sequence multiple testing procedure was used to control the overall Type I error rate at the 0.05 level (2-sided) for the primary endpoints analyses. Analyses appear in the defined sequence. This is the sixth in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments [Not Specified]
Method ANCOVA
Comments Effects due to baseline trough AM FEV1, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.266
Confidence Interval (2-Sided) 95%
0.172 to 0.360
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
Comments A fixed-sequence multiple testing procedure was used to control the overall Type I error rate at the 0.05 level (2-sided) for the primary endpoints analyses. Analyses appear in the defined sequence. This is the seventh in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method ANCOVA
Comments Effects due to baseline trough AM FEV1, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.151
Confidence Interval (2-Sided) 95%
0.057 to 0.244
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
Comments A fixed-sequence multiple testing procedure was used to control the overall Type I error rate at the 0.05 level (2-sided) for the primary endpoints analyses. Analyses appear in the defined sequence. This is the eighth in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0132
Comments [Not Specified]
Method ANCOVA
Comments Effects due to baseline trough AM FEV1, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.119
Confidence Interval (2-Sided) 95%
0.025 to 0.212
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in the Weekly Average of the Daily Morning Trough Peak Expiratory Flow (PEF) Over the 12 Week Treatment
Hide Description Morning PEF tests were performed before administration of study drug or rescue medications (data were excluded if the time of PEF measurement was more than 5 minutes after the dose time). The patient recorded the highest value of 3 measurements obtained in the patient diary. The baseline PEF was the average value of recorded (nonmissing) morning assessments over the 7 days prior to randomization on Day 1. For efficacy analyses of weekly average morning PEF measurements, values were the averages based on available data for that week.
Time Frame Days -6 to Day 1 (predose), Day 1 (postdose) daily until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set of patients who contributed at least once to the analysis.
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 125 128 129 128 128
Least Squares Mean (Standard Error)
Unit of Measure: liters/minute
24.415  (3.1530) 24.864  (3.1182) 14.517  (3.0778) 10.609  (3.1176) 3.591  (3.1474)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
Comments The analysis of change from baseline in weekly average of daily (AM predose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using an mixed model for repeated measures (MMRM) with an unstructured covariance matrix and with effects due to baseline weekly average of daily AM PEF, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0123
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 10.926
Confidence Interval (2-Sided) 95%
2.380 to 19.471
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
Comments The analysis of change from baseline in weekly average of daily (AM predose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using an mixed model for repeated measures (MMRM) with an unstructured covariance matrix and with effects due to baseline weekly average of daily AM PEF, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1074
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 7.018
Confidence Interval (2-Sided) 95%
-1.531 to 15.567
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Placebo MDPI
Comments The analysis of change from baseline in weekly average of daily (AM predose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using an mixed model for repeated measures (MMRM) with an unstructured covariance matrix and with effects due to baseline weekly average of daily AM PEF, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 20.824
Confidence Interval (2-Sided) 95%
12.253 to 29.395
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Placebo MDPI
Comments The analysis of change from baseline in weekly average of daily (AM predose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using an mixed model for repeated measures (MMRM) with an unstructured covariance matrix and with effects due to baseline weekly average of daily AM PEF, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 21.273
Confidence Interval (2-Sided) 95%
12.728 to 29.818
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 100 mcg
Comments The analysis of change from baseline in weekly average of daily (AM predose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using an mixed model for repeated measures (MMRM) with an unstructured covariance matrix and with effects due to baseline weekly average of daily AM PEF, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0233
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 9.898
Confidence Interval (2-Sided) 95%
1.349 to 18.447
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 50 mcg
Comments The analysis of change from baseline in weekly average of daily (AM predose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using an mixed model for repeated measures (MMRM) with an unstructured covariance matrix and with effects due to baseline weekly average of daily AM PEF, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 14.255
Confidence Interval (2-Sided) 95%
5.732 to 22.778
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 100 mcg
Comments The analysis of change from baseline in weekly average of daily (AM predose and pre-rescue bronchodilator) PEF over the 12-week treatment period was performed using an mixed model for repeated measures (MMRM) with an unstructured covariance matrix and with effects due to baseline weekly average of daily AM PEF, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0175
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 10.347
Confidence Interval (2-Sided) 95%
1.822 to 18.872
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over the 12-Week Treatment Period
Hide Description

The total daily asthma symptom score is the average of the daytime and nighttime scores as recorded in the patient diary (range 0-9).

Daytime Symptom Score:

0=No symptoms

  1. Symptoms for 1 short period
  2. Symptoms for 2+ short periods
  3. Symptoms for most of the day - did not affect normal daily activities
  4. Symptoms for most of the day - did affect normal daily activities
  5. Symptoms so severe that I could not go to work or perform normal daily activities

Nighttime Symptom Score (determined in the AM):

0=No symptoms

  1. Symptoms causing me to wake once (or wake early)
  2. Symptoms causing me to wake twice or more (including waking early)
  3. Symptoms causing me to be awake for most of the night
  4. Symptoms so severe that I did not sleep Baseline was the average of recorded scores over the 7 days before randomization. The change from baseline in the weekly average over weeks 1 to 12 was analyzed using an mixed model for repeated measures (MMRM).
Time Frame Days -6 to Day 1 (predose, baseline) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set of patients who contributed at least once to the analysis.
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 125 128 129 128 128
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.364  (0.0318) -0.329  (0.0314) -0.300  (0.0308) -0.278  (0.0314) -0.135  (0.0318)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
Comments The change from baseline in the weekly average of the total daily asthma symptom scores over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.165
Confidence Interval (2-Sided) 95%
-0.251 to -0.080
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
Comments The change from baseline in the weekly average of the total daily asthma symptom scores over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.143
Confidence Interval (2-Sided) 95%
-0.229 to -0.058
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Placebo MDPI
Comments The change from baseline in the weekly average of the total daily asthma symptom scores over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.230
Confidence Interval (2-Sided) 95%
-0.315 to -0.144
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Placebo MDPI
Comments The change from baseline in the weekly average of the total daily asthma symptom scores over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.194
Confidence Interval (2-Sided) 95%
-0.279 to -0.109
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 100 mcg
Comments The change from baseline in the weekly average of the total daily asthma symptom scores over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1381
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.064
Confidence Interval (2-Sided) 95%
-0.150 to 0.021
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 50 mcg
Comments The change from baseline in the weekly average of the total daily asthma symptom scores over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2438
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.051
Confidence Interval (2-Sided) 95%
-0.136 to 0.035
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 100 mcg
Comments The change from baseline in the weekly average of the total daily asthma symptom scores over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5095
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.029
Confidence Interval (2-Sided) 95%
-0.114 to 0.057
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in the Weekly Average of the Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol Over the 12-Week Treatment Period
Hide Description Patients recorded the number of inhalations of rescue medication (albuterol/salbutamol HFA MDI) each AM and PM in the diary. The average number of daily inhalations over the 7 days before the randomization visit was the baseline value. The weekly average was based on the available data for the 7 days before each analysis week. The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using a mixed model for repeated measures.
Time Frame Days -6 to Day 1 (predose, baseline), up to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS of patients who contributed at least once to the analysis
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 126 128 129 128 129
Least Squares Mean (Standard Error)
Unit of Measure: puffs
-0.677  (0.0937) -0.706  (0.0930) -0.466  (0.0915) -0.467  (0.0928) -0.003  (0.0937)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
Comments The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline value, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments Significance level of 0.05
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.463
Confidence Interval (2-Sided) 95%
-0.716 to -0.209
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
Comments The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline value, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments Significance level of 0.05
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.464
Confidence Interval (2-Sided) 95%
-0.718 to -0.211
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Placebo MDPI
Comments The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline value, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Significance level of 0.05
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.675
Confidence Interval (2-Sided) 95%
-0.928 to -0.421
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Placebo MDPI
Comments The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline value, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Significance level of 0.05
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.704
Confidence Interval (2-Sided) 95%
-0.957 to -0.450
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 100 mcg
Comments The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline value, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1014
Comments Significance level of 0.05
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.212
Confidence Interval (2-Sided) 95%
-0.465 to 0.042
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 50 mcg
Comments The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline value, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0640
Comments Significance level of 0.05
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.239
Confidence Interval (2-Sided) 95%
-0.492 to 0.014
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 100 mcg
Comments The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using an MMRM with an unstructured covariance matrix and with effects due to baseline value, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), week, treatment, and week-by-treatment interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0626
Comments Significance level of 0.05
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.241
Confidence Interval (2-Sided) 95%
-0.494 to 0.013
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Kaplan-Meier Estimate of Probability of Remaining in Study At Week 12
Hide Description The analysis of probability of remaining in the study at Week 12 used the time to patient withdrawal for worsening asthma, defined as the number of days elapsed from the date of randomization to the date of withdrawal due to worsening asthma. Patients who were lost to follow-up, who had not withdrawn due to worsening asthma by week 12, or who had withdrawn due to reasons other than worsening asthma were right-censored at the date of last assessment.
Time Frame up to Week 12 of the Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 126 128 129 128 129
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
1.0000
(1.000 to 1.000)
0.9917
(0.942 to 0.999)
0.9919
(0.944 to 0.999)
0.9919
(0.944 to 0.999)
0.9681
(0.917 to 0.988)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1679
Comments Significance level of 0.05
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1701
Comments Significance level of 0.05
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Placebo MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0437
Comments Significance level of 0.05
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Placebo MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1718
Comments Significance level of 0.05
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 100 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3134
Comments Significance level of 0.05
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 50 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9930
Comments Significance level of 0.05
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 100 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9999
Comments Significance level of 0.05
Method Log Rank
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ(S)) Score at Endpoint for Patients >=18 Years Old
Hide Description

The AQLQ(S) (September 2010 version; patients aged ≥18 years) was self-administered by the patients at the investigational center at the randomization visit and at Week 12 or end of trial. The questionnaire is a tool to measure the impact of asthma on a patient’s quality of life (physical, emotional, social, and occupational) with a recall period of 2 weeks. The AQLQ(S) was administered only to patients 18 years and older. The 32 individual questions in the AQLQ were equally weighted. The overall AQLQ score was the mean of the responses to each of the 32 questions, and ranged from 1 to 7. A score of 7.0 indicated that the patient had no impairments due to asthma and a score of 1.0 indicated severe impairment.

Positive change from baseline scores indicate improved quality of life.

Time Frame Day 1 (predose, baseline), end of trial (up to week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS patients who contributed at least once to analysis and were >= 18 years old
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 109 102 103 108 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.808  (0.0728) 0.565  (0.0752) 0.636  (0.0736) 0.588  (0.0733) 0.335  (0.0777)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Placebo MDPI
Comments The change from baseline in AQLQ(S) score (patients ≥18 years of age) at endpoint (ie, last postbaseline observation) was analyzed using an ANCOVA model with effects due to baseline AQLQ(S) score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment, imputing missing data via last observation carried forward (LOCF).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0044
Comments Significance level of 0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.301
Confidence Interval (2-Sided) 95%
0.094 to 0.508
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fp MDPI 50 mcg, Placebo MDPI
Comments The change from baseline in AQLQ(S) score (patients ≥18 years of age) at endpoint (ie, last postbaseline observation) was analyzed using an ANCOVA model with effects due to baseline AQLQ(S) score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment, imputing missing data via last observation carried forward (LOCF).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0155
Comments Significance level of 0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.253
Confidence Interval (2-Sided) 95%
0.048 to 0.458
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Placebo MDPI
Comments The change from baseline in AQLQ(S) score (patients ≥18 years of age) at endpoint (ie, last postbaseline observation) was analyzed using an ANCOVA model with effects due to baseline AQLQ(S) score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment, imputing missing data via last observation carried forward (LOCF).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Significance level of 0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.473
Confidence Interval (2-Sided) 95%
0.270 to 0.676
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Placebo MDPI
Comments The change from baseline in AQLQ(S) score (patients ≥18 years of age) at endpoint (ie, last postbaseline observation) was analyzed using an ANCOVA model with effects due to baseline AQLQ(S) score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment, imputing missing data via last observation carried forward (LOCF).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0293
Comments Significance level of 0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.230
Confidence Interval (2-Sided) 95%
0.023 to 0.437
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 100 mcg
Comments The change from baseline in AQLQ(S) score (patients ≥18 years of age) at endpoint (ie, last postbaseline observation) was analyzed using an ANCOVA model with effects due to baseline AQLQ(S) score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment, imputing missing data via last observation carried forward (LOCF).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0913
Comments Significance level of 0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.172
Confidence Interval (2-Sided) 95%
-0.028 to 0.372
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 50 mcg
Comments The change from baseline in AQLQ(S) score (patients ≥18 years of age) at endpoint (ie, last postbaseline observation) was analyzed using an ANCOVA model with effects due to baseline AQLQ(S) score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment, imputing missing data via last observation carried forward (LOCF).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8216
Comments Significance level of 0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.023
Confidence Interval (2-Sided) 95%
-0.223 to 0.177
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 50 / 12.5 mcg, Fp MDPI 100 mcg
Comments The change from baseline in AQLQ(S) score (patients ≥18 years of age) at endpoint (ie, last postbaseline observation) was analyzed using an ANCOVA model with effects due to baseline AQLQ(S) score, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment, imputing missing data via last observation carried forward (LOCF).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4934
Comments Significance level of 0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.071
Confidence Interval (2-Sided) 95%
-0.275 to 0.133
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Kaplan-Meier Estimates for Time to 15% and 12% Improvement From Baseline in FEV1 Postdose on Day 1
Hide Description

A subset of approximately 300 patients who performed postdose serial spirometry is based on sample size calculation. Baseline FEV1 was the average of 2 FEV1 measurements (30 and 10 minutes predose) on Day 1. If one of these was missing, the other measurement was used as baseline value. If both were missing, baseline was treated as missing. Time to target improvement (15% or 12%) was defined as the time elapsed from the time of first dose to the first time the target improvement in FEV1 was achieved. If an exact target increase was not achieved at a measured timepoint, then the time was estimated by linear interpolation between the timepoint when target was reached and the timepoint immediately before. Patients who did not achieve the target improvement were censored at the time of last serial spirometry assessment.

Values of 9999 indicate the values could not be estimated which happened when the estimated probability of not achieving target is more than 50%.

Time Frame Day 1 of the Treatment Period (predose and postdose)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: a subset of patients who performed postdose serial spirometry on Day 1
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 61 56 72 63 60
Median (95% Confidence Interval)
Unit of Measure: hours
15% improvement
4.3 [1] 
(1.070 to NA)
1.3
(0.600 to 2.750)
NA [1] 
(10.190 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
12% improvement
1.0
(0.460 to 3.720)
0.5
(0.300 to 1.550)
NA [1] 
(7.370 to NA)
NA [1] 
(3.890 to NA)
NA [1] 
(7.270 to NA)
[1]
values could not be estimated which happened when the estimated probability of not achieving target is more than 50%.
9.Secondary Outcome
Title Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period
Hide Description An adverse event was defined 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 AE which prevents normal daily activities. Relationship 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.
Time Frame Day 1 to Week 12 of the Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description:

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Overall Number of Participants Analyzed 126 128 129 129 129
Measure Type: Count of Participants
Unit of Measure: Participants
>=1 TEAE
37
  29.4%
46
  35.9%
40
  31.0%
44
  34.1%
47
  36.4%
>=1 severe TEAE
2
   1.6%
0
   0.0%
1
   0.8%
1
   0.8%
0
   0.0%
>=1 treatment-related TEAE
4
   3.2%
4
   3.1%
5
   3.9%
7
   5.4%
5
   3.9%
>=1 severe treatment-related TEAE
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=1 serious TEAE
1
   0.8%
0
   0.0%
1
   0.8%
0
   0.0%
2
   1.6%
>=1 TEAE leading to withdrawal
0
   0.0%
3
   2.3%
2
   1.6%
1
   0.8%
6
   4.7%
>=1 nonserious TEAE
36
  28.6%
46
  35.9%
39
  30.2%
44
  34.1%
45
  34.9%
>=1 TEAE resulting in death
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame Day 1 up to Week 12
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Hide Arm/Group Description

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 200 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate for a total daily dose of 100 mcg for 12 weeks.

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

The placebo multidose dry powder inhaler was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart).

Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

All-Cause Mortality
FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/126 (0.79%)      0/128 (0.00%)      1/129 (0.78%)      0/129 (0.00%)      2/129 (1.55%)    
Gastrointestinal disorders           
Pancreatitis  1  1/126 (0.79%)  1 0/128 (0.00%)  0 0/129 (0.00%)  0 0/129 (0.00%)  0 0/129 (0.00%)  0
Hepatobiliary disorders           
Cholecystitis  1  1/126 (0.79%)  1 0/128 (0.00%)  0 0/129 (0.00%)  0 0/129 (0.00%)  0 0/129 (0.00%)  0
Cholelithiasis  1  1/126 (0.79%)  1 0/128 (0.00%)  0 0/129 (0.00%)  0 0/129 (0.00%)  0 0/129 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Plasma cell myeloma  1  0/126 (0.00%)  0 0/128 (0.00%)  0 1/129 (0.78%)  1 0/129 (0.00%)  0 0/129 (0.00%)  0
Pregnancy, puerperium and perinatal conditions           
Abortion spontaneous  1  0/126 (0.00%)  0 0/128 (0.00%)  0 0/129 (0.00%)  0 0/129 (0.00%)  0 1/129 (0.78%)  1
Respiratory, thoracic and mediastinal disorders           
Asthma  1  0/126 (0.00%)  0 0/128 (0.00%)  0 0/129 (0.00%)  0 0/129 (0.00%)  0 1/129 (0.78%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FS MDPI 100 / 12.5 mcg FS MDPI 50 / 12.5 mcg Fp MDPI 100 mcg Fp MDPI 50 mcg Placebo MDPI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/126 (9.52%)      22/128 (17.19%)      21/129 (16.28%)      15/129 (11.63%)      15/129 (11.63%)    
Infections and infestations           
Nasopharyngitis  1  3/126 (2.38%)  3 11/128 (8.59%)  11 9/129 (6.98%)  10 7/129 (5.43%)  8 4/129 (3.10%)  5
Upper respiratory tract infection  1  2/126 (1.59%)  2 6/128 (4.69%)  6 4/129 (3.10%)  4 7/129 (5.43%)  8 6/129 (4.65%)  6
Nervous system disorders           
Headache  1  7/126 (5.56%)  10 7/128 (5.47%)  8 9/129 (6.98%)  11 2/129 (1.55%)  4 5/129 (3.88%)  7
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
EMail: ustevatrials@tevapharm.com
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT02139644     History of Changes
Other Study ID Numbers: FSS-AS-301
2014-001149-25 ( EudraCT Number )
First Submitted: May 9, 2014
First Posted: May 15, 2014
Results First Submitted: February 28, 2017
Results First Posted: April 12, 2017
Last Update Posted: April 12, 2017