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Efficacy and Safety Study of FP MDPI Compared With FS 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: NCT02141854
Recruitment Status : Completed
First Posted : May 20, 2014
Results First Posted : April 12, 2017
Last Update Posted : May 31, 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/salmeterol HFA MDI
Enrollment 882
Recruitment Details  
Pre-assignment Details A total of 1661 patients with persistent asthma were screened and 882 patients enrolled. 154 patients were not randomized, most commonly (76 patients) because of not meeting randomization criteria.
Arm/Group Title Fluticasone Propionate 50 mcg BID FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description All enrolled participants used single-blind fluticasone propionate multidose dry powder inhaler twice a day for a total daily dose of 100 mcg during the Run-In Period (14-21 days).

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 882 0 0 0 0 0
Completed 728 0 0 0 0 0
Not Completed 154 0 0 0 0 0
Reason Not Completed
Inclusion criteria not met             25             0             0             0             0             0
Randomization criteria not met             76             0             0             0             0             0
Exclusion criteria met             14             0             0             0             0             0
Not specified             14             0             0             0             0             0
Adverse Event             10             0             0             0             0             0
Withdrawal by Subject             9             0             0             0             0             0
Lost to Follow-up             6             0             0             0             0             0
Period Title: Treatment Period
Started 0 146 145 146 146 145
Intent to Treat Population 0 146 145 146 146 145
Safety Population 0 145 143 146 145 144
Full Analysis Set 0 145 141 146 145 143
Completed 0 136 136 135 136 107
Not Completed 0 10 9 11 10 38
Reason Not Completed
Protocol Violation             0             1             0             2             2             1
Noncompliance             0             0             0             1             0             0
Lack of Efficacy             0             0             0             1             1             7
Pregnancy             0             1             0             0             0             0
Not specified             0             1             2             0             1             2
Adverse Event             0             2             2             0             2             2
Withdrawal by Subject             0             2             3             3             4             7
Disease progression             0             2             1             3             0             18
Lost to Follow-up             0             1             1             1             0             1
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI Total
Hide Arm/Group Description

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 146 145 146 146 145 728
Hide Baseline Analysis Population Description
Randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
44.7  (16.93) 44.3  (14.88) 44.4  (16.36) 45.7  (15.64) 44.5  (16.05) 44.7  (15.95)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Adolescents (12-17 years) Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
12
   8.2%
8
   5.5%
10
   6.8%
9
   6.2%
6
   4.1%
45
   6.2%
Adults (18-64 years) Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
115
  78.8%
125
  86.2%
119
  81.5%
124
  84.9%
125
  86.2%
608
  83.5%
Adults (65-84 years) Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
19
  13.0%
12
   8.3%
17
  11.6%
13
   8.9%
14
   9.7%
75
  10.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
Female
87
  59.6%
79
  54.5%
88
  60.3%
94
  64.4%
91
  62.8%
439
  60.3%
Male
59
  40.4%
66
  45.5%
58
  39.7%
52
  35.6%
54
  37.2%
289
  39.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
125
  85.6%
112
  77.2%
116
  79.5%
111
  76.0%
124
  85.5%
588
  80.8%
Black or African American Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
20
  13.7%
28
  19.3%
23
  15.8%
31
  21.2%
18
  12.4%
120
  16.5%
Asian Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
0
   0.0%
0
   0.0%
2
   1.4%
0
   0.0%
2
   1.4%
4
   0.5%
American Indian or Alaskan Native Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
0
   0.0%
0
   0.0%
2
   1.4%
0
   0.0%
0
   0.0%
2
   0.3%
Native Hawaiian or Other Pacific Islander Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Other Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
1
   0.7%
5
   3.4%
3
   2.1%
4
   2.7%
1
   0.7%
14
   1.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Not Hispanic or Latino Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
136
  93.2%
135
  93.1%
136
  93.2%
134
  91.8%
136
  93.8%
677
  93.0%
Hispanic or Latino Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
10
   6.8%
10
   6.9%
10
   6.8%
11
   7.5%
8
   5.5%
49
   6.7%
Unknown Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.7%
1
   0.7%
2
   0.3%
History of Smoking  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
Prior Smoker
20
  13.7%
28
  19.3%
21
  14.4%
28
  19.2%
23
  15.9%
120
  16.5%
No tobacco use
126
  86.3%
117
  80.7%
125
  85.6%
118
  80.8%
122
  84.1%
608
  83.5%
Previous Asthma Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
Inhaled corticosteroid
73
  50.0%
67
  46.2%
63
  43.2%
58
  39.7%
68
  46.9%
329
  45.2%
Inhaled corticosteroid/long-acting beta2-agonist
73
  50.0%
78
  53.8%
83
  56.8%
88
  60.3%
77
  53.1%
399
  54.8%
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 146 participants 145 participants 146 participants 146 participants 145 participants 728 participants
29.4  (7.35) 30.2  (7.60) 29.9  (7.27) 29.9  (7.62) 29.3  (7.41) 29.7  (7.44)
Forced Expiratory Volume in 1 second (FEV1)   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters
Number Analyzed 145 participants 142 participants 146 participants 145 participants 144 participants 722 participants
2.083  (0.6532) 2.157  (0.6402) 2.075  (0.5696) 2.069  (0.6017) 2.141  (0.6849) 2.105  (0.6303)
[1]
Measure Analysis Population Description: Some participants were missing baseline values
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 AUEC0-12) at Week 12
Hide Description A subset of patients performed postdose serial spirometry. 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
A subset of patients who performed postdose serial spirometry at the baseline visit and week 12.
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 68 58 61 64 61
Least Squares Mean (Standard Error)
Unit of Measure: liters
0.446  (0.0463) 0.442  (0.0496) 0.267  (0.0466) 0.260  (0.0463) 0.121  (0.0472)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 12.5 mcg, Fp MDPI 200 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 0.0009
Comments Fixed effects of treatment, sex, (pooled) center, previous therapy (ICS or ICS/LABA), and covariates of age and baseline FEV1.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.179
Confidence Interval (2-Sided) 95%
0.074 to 0.285
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 second in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments Fixed effects of treatment, sex, (pooled) center, previous therapy (ICS or ICS/LABA), and covariates of age and baseline FEV1.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.182
Confidence Interval (2-Sided) 95%
0.074 to 0.291
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 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 Fixed effects of treatment, sex, (pooled) center, previous therapy (ICS or ICS/LABA), and covariates of age and baseline FEV1.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.326
Confidence Interval (2-Sided) 95%
0.221 to 0.431
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 fourth in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Fixed effects of treatment, sex, (pooled) center, previous therapy (ICS or ICS/LABA), and covariates of age and baseline FEV1.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.322
Confidence Interval (2-Sided) 95%
0.212 to 0.432
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 is a morning spirometry taken predose and pre-rescue bronchodilator. 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
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.
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 143 140 145 144 143
Least Squares Mean (Standard Error)
Unit of Measure: liters
0.272  (0.0307) 0.271  (0.0311) 0.179  (0.0308) 0.119  (0.0311) -0.004  (0.0312)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 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 Effects due to baseline trough AM FEV1, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.276
Confidence Interval (2-Sided) 95%
0.191 to 0.361
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 sixth in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments Effects due to baseline trough AM FEV1, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.274
Confidence Interval (2-Sided) 95%
0.189 to 0.360
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 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 0.0000
Comments Effects due to baseline trough AM FEV1, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.183
Confidence Interval (2-Sided) 95%
0.098 to 0.268
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 eighth in the sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0047
Comments Effects due to baseline trough AM FEV1, sex, age, (pooled) center, previous therapy (ICS or ICS/LABA), and treatment.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.123
Confidence Interval (2-Sided) 95%
0.038 to 0.208
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, baseline), Day 1 (postdose) daily until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 145 141 146 145 142
Least Squares Mean (Standard Error)
Unit of Measure: liters/minute
20.235  (2.3845) 18.610  (2.4137) 7.464  (2.3887) 5.731  (2.4102) -10.987  (2.4784)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 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 18.450
Confidence Interval (2-Sided) 95%
11.751 to 25.150
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.0000
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 16.718
Confidence Interval (2-Sided) 95%
9.988 to 23.449
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 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 31.221
Confidence Interval (2-Sided) 95%
24.513 to 37.930
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 29.597
Confidence Interval (2-Sided) 95%
22.839 to 36.354
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 12.5 mcg, Fp MDPI 200 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 0.0002
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 12.771
Confidence Interval (2-Sided) 95%
6.179 to 19.363
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
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 0.0002
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 12.879
Confidence Interval (2-Sided) 95%
6.216 to 19.541
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 200 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 0.0010
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 11.146
Confidence Interval (2-Sided) 95%
4.511 to 17.782
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.

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
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 145 141 146 145 142
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.391  (0.0328) -0.364  (0.0332) -0.242  (0.0329) -0.282  (0.0333) -0.087  (0.0342)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 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 -0.156
Confidence Interval (2-Sided) 95%
-0.248 to -0.063
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.0000
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.195
Confidence Interval (2-Sided) 95%
-0.288 to -0.102
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 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 -0.304
Confidence Interval (2-Sided) 95%
-0.397 to -0.212
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 -0.277
Confidence Interval (2-Sided) 95%
-0.370 to -0.184
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 12.5 mcg, Fp MDPI 200 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 0.0014
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.149
Confidence Interval (2-Sided) 95%
-0.239 to -0.058
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
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 0.0818
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.082
Confidence Interval (2-Sided) 95%
-0.174 to 0.010
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 200 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 0.0094
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.121
Confidence Interval (2-Sided) 95%
-0.213 to -0.030
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
Full analysis set
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 145 141 146 145 143
Least Squares Mean (Standard Error)
Unit of Measure: puffs
-0.898  (0.1069) -0.821  (0.1080) -0.534  (0.1070) -0.439  (0.1081) 0.168  (0.1102)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 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 -0.702
Confidence Interval (2-Sided) 95%
-1.001 to -0.403
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.0001
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.607
Confidence Interval (2-Sided) 95%
-0.908 to -0.307
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 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 -1.066
Confidence Interval (2-Sided) 95%
-1.365 to -0.766
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 -0.989
Confidence Interval (2-Sided) 95%
-1.291 to -0.686
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 12.5 mcg, Fp MDPI 200 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 0.0160
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.364
Confidence Interval (2-Sided) 95%
-0.659 to -0.068
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
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 0.0124
Comments Significance level of 0.05.
Method mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.382
Confidence Interval (2-Sided) 95%
-0.681 to -0.083
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 200 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 0.0588
Comments Significance level of 0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.287
Confidence Interval (2-Sided) 95%
-0.584 to 0.011
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
Full analysis set
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 145 141 146 145 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
0.9719
(0.927 to 0.989)
0.9929
(0.950 to 0.999)
0.9786
(0.935 to 0.993)
0.9930
(0.951 to 0.999)
0.8528
(0.781 to 0.903)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 mcg, Placebo MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
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 100 mcg, Placebo MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
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 200 / 12.5 mcg, Placebo MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
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 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 <.0001
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 200 / 12.5 mcg, Fp MDPI 200 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7203
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 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 0.9960
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 100 / 12.5 mcg, Fp MDPI 200 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3250
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 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
Full analysis set of participants who contributed at least once to analysis and were >= 18 years old
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 131 135 132 133 129
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.534  (0.0741) 0.592  (0.0725) 0.384  (0.0742) 0.340  (0.0740) -0.089  (0.0747)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 200 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%
0.269 to 0.677
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.0000
Comments Significance level of 0.05.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.428
Confidence Interval (2-Sided) 95%
0.224 to 0.632
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 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 0.623
Confidence Interval (2-Sided) 95%
0.418 to 0.828
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 Slope
Estimated Value 0.681
Confidence Interval (2-Sided) 95%
0.478 to 0.885
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FS MDPI 200 / 12.5 mcg, Fp MDPI 200 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 0.1490
Comments Significance level of 0.05.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.150
Confidence Interval (2-Sided) 95%
-0.054 to 0.354
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
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 0.0143
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%
0.051 to 0.455
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 100 / 12.5 mcg, Fp MDPI 200 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 0.0435
Comments Significance level of 0.05.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.209
Confidence Interval (2-Sided) 95%
0.006 to 0.411
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

The baseline forced expiratory volume in 1 second (FEV1) was the average of the 2 predose 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, the baseline trough FEV1 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 NA 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
Patients who did not achieve the target improvement were censored at the time of last serial spirometry assessment.
Arm/Group Title FS MDPI 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 68 58 61 64 61
Median (95% Confidence Interval)
Unit of Measure: hours
15% improvement
0.8
(0.310 to 1.770)
0.9
(0.480 to 11.960)
NA [1] 
(3.840 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
12% improvement
0.4
(0.250 to 0.810)
0.4
(0.290 to 1.680)
6.9 [1] 
(2.690 to NA)
NA [1] 
(5.580 to NA)
NA [1] 
(5.680 to NA)
[1]
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. 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.
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 200 / 12.5 mcg FS MDPI 100 / 12.5 mcg Fp MDPI 200 mcg Fp MDPI 100 mcg Placebo MDPI
Hide Arm/Group Description:

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 145 143 146 145 144
Measure Type: Count of Participants
Unit of Measure: Participants
>=1 TEAE
61
  42.1%
59
  41.3%
60
  41.1%
53
  36.6%
52
  36.1%
>=1 severe TEAE
3
   2.1%
2
   1.4%
0
   0.0%
1
   0.7%
1
   0.7%
>=1 treatment-related TEAE
8
   5.5%
4
   2.8%
9
   6.2%
6
   4.1%
5
   3.5%
>=1 severe treatment-related TEAE
1
   0.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=1 serious TEAE
2
   1.4%
2
   1.4%
1
   0.7%
1
   0.7%
1
   0.7%
>=1 TEAE leading to withdrawal
2
   1.4%
2
   1.4%
0
   0.0%
2
   1.4%
2
   1.4%
>=1 nonserious TEAE
61
  42.1%
58
  40.6%
60
  41.1%
52
  35.9%
52
  36.1%
>=1 TEAE resulting in death
0
   0.0%
1
   0.7%
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame Day 1 up to Week 14
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title FS MDPI 100/12.5 mcg FS MDPI 200/12.5 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Placebo
Hide Arm/Group Description

Following randomization, participants in this treatment arm 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/salmeterol HFA MDI: Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Following randomization, participants in this treatment arm took 1 inhalation twice a day using a multidose dry powder inhaler (MDPI) of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

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

Following randomization, participants in this treatment arm took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Albuterol/salmeterol HFA MDI: Albuterol/salmeterol 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 200/12.5 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Placebo
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 200/12.5 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/143 (1.40%)      2/145 (1.38%)      1/145 (0.69%)      1/146 (0.68%)      1/144 (0.69%)    
General disorders           
Pyrexia  1  0/143 (0.00%)  0 0/145 (0.00%)  0 0/145 (0.00%)  0 1/146 (0.68%)  1 0/144 (0.00%)  0
Hepatobiliary disorders           
Jaundice  1  1/143 (0.70%)  1 0/145 (0.00%)  0 0/145 (0.00%)  0 0/146 (0.00%)  0 0/144 (0.00%)  0
Infections and infestations           
Pneumonia  1  0/143 (0.00%)  0 1/145 (0.69%)  1 0/145 (0.00%)  0 0/146 (0.00%)  0 0/144 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Breast cancer  1  1/143 (0.70%)  1 0/145 (0.00%)  0 0/145 (0.00%)  0 0/146 (0.00%)  0 0/144 (0.00%)  0
Nervous system disorders           
Grand mal convulsion  1  0/143 (0.00%)  0 0/145 (0.00%)  0 1/145 (0.69%)  1 0/146 (0.00%)  0 0/144 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Asthma  1  0/143 (0.00%)  0 1/145 (0.69%)  1 0/145 (0.00%)  0 0/146 (0.00%)  0 1/144 (0.69%)  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 200/12.5 mcg Fp MDPI 100 mcg Fp MDPI 200 mcg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/143 (14.69%)      20/145 (13.79%)      26/145 (17.93%)      20/146 (13.70%)      20/144 (13.89%)    
Infections and infestations           
Nasopharyngitis  1  10/143 (6.99%)  10 10/145 (6.90%)  12 7/145 (4.83%)  7 7/146 (4.79%)  8 8/144 (5.56%)  9
Upper respiratory tract infection  1  6/143 (4.20%)  6 6/145 (4.14%)  6 9/145 (6.21%)  11 8/146 (5.48%)  9 7/144 (4.86%)  7
Nervous system disorders           
Headache  1  6/143 (4.20%)  21 4/145 (2.76%)  5 11/145 (7.59%)  18 7/146 (4.79%)  7 7/144 (4.86%)  10
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: NCT02141854     History of Changes
Other Study ID Numbers: FSS-AS-30017
2014-000923-25 ( EudraCT Number )
First Submitted: May 9, 2014
First Posted: May 20, 2014
Results First Submitted: February 28, 2017
Results First Posted: April 12, 2017
Last Update Posted: May 31, 2017