Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 84 of 318 for:    FLUTICASONE AND SALMETEROL

Dose Ranging Study of the Salmeterol Component of Fluticasone /Salmeterol Spiromax Compared to Fluticasone Spiromax and Advair Diskus in Asthma Subjects

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: NCT01772368
Recruitment Status : Completed
First Posted : January 21, 2013
Results First Posted : April 12, 2017
Last Update Posted : June 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: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Fp MDPI
Drug: FS MDPI
Drug: Advair Diskus
Drug: Albuterol
Enrollment 72
Recruitment Details A total of 105 subjects with asthma were screened for this study. Of the 105 subjects screened, 82 subjects at 10 investigational sites in the US met entry criteria and were considered to be eligible to enter the run-in period.
Pre-assignment Details Ten subjects failed randomization.
Arm/Group Title All Participants
Hide Arm/Group Description All subjects, regardless of the order of treatments to which they were randomized in this cross-over study.
Period Title: Overall Study
Started 72
Received Fp MDPI 100 mcg 67
Received FS MDPI 100/6.25 mcg 68
Received FS MDPI 100/12.5mcg 69
Received FS MDPI 100/25 mcg 67
Received FS MDPI 100/50 mcg 68
Received Advair Diskus 100/50 mcg 66
Completed 65
Not Completed 7
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             3
Protocol Violation             2
Not specified             1
Arm/Group Title All Participants
Hide Arm/Group Description All subjects, regardless of the order of treatments to which they were randomized in this cross-over study.
Overall Number of Baseline Participants 72
Hide Baseline Analysis Population Description
Intent-to-Treat population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants
42.5  (13.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
Female
37
  51.4%
Male
35
  48.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
White
64
  88.9%
Black
7
   9.7%
Other
1
   1.4%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 72 participants
79.2  (14.17)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 72 participants
170.0  (9.76)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 72 participants
27.3  (3.35)
1.Primary Outcome
Title Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12)
Hide Description Standardized baseline-adjusted FEV1 AUC0-12 was defined as the area under the curve for baseline-adjusted FEV1 measurements from the predose to 12 hours postdose time points using the trapezoidal rule based on actual (not scheduled) time of measurement and was standardized by dividing the actual time of last non-missing FEV1 measurement. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting period-specific baseline FEV1. The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline.
Time Frame Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all subjects in the ITT population who received at least 1 dose of study drug and had at least 1 evaluable standardized baseline-adjusted FEV1 AUC0-12.
Arm/Group Title Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg
Hide Arm/Group Description:
Subjects inhaled a single dose of 100 mcg fluticasone propionate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
Overall Number of Participants Analyzed 67 68 69 67 68 66
Least Squares Mean (Standard Error)
Unit of Measure: mL
52.13  (38.071) 203.84  (38.072) 248.98  (38.025) 279.69  (38.121) 303.43  (38.062) 245.56  (38.148)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/6.25 mcg, FS MDPI 100/12.5mcg, FS MDPI 100/25 mcg, FS MDPI 100/50 mcg
Comments A linear in log-dose-trend contrast was constructed to evaluate the dose-response trend, where the logarithm of dose was defined precisely as log (dose+1) to accommodate the case of Fp MDPI 100 mcg, since the dose used in this trend analysis was the salmeterol dose. The study was considered positive if the trend test was positive and the test involving the highest FS MDPI dose (100/50 mcg) compared with Fp MDPI 100 mcg was positive, regardless of the results of the tests for the other doses.
Type of Statistical Test Other
Comments linearity statistical test
Statistical Test of Hypothesis P-Value <0.0001
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between FS MDPI 100/50 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 251.30
Confidence Interval (2-Sided) 95%
215.6 to 287.1
Estimation Comments FS MDPI 100/50 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/25 mcg
Comments The estimated treatment difference from the ANCOVA model between FS MDPI 100/25 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 227.56
Confidence Interval (2-Sided) 95%
191.6 to 263.5
Estimation Comments FS MDPI 100/25 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/12.5mcg
Comments The estimated treatment difference from the ANCOVA model between FS MDPI 100/512.5 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 196.85
Confidence Interval (2-Sided) 95%
161.2 to 232.5
Estimation Comments FS MDPI 100/12.5 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/6.25 mcg
Comments The estimated treatment difference from the ANCOVA model between FS MDPI 100/6.25 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 151.71
Confidence Interval (2-Sided) 95%
115.9 to 187.5
Estimation Comments FS MDPI 100/6.25 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between Advair Diskus 100/50 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 193.42
Confidence Interval (2-Sided) 95%
157.4 to 229.5
Estimation Comments Advair Diskus 100/50 mcg - Fp MDPI 100
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/50 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between FS MDPI 100/50 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 57.88
Confidence Interval (2-Sided) 95%
22.0 to 93.7
Estimation Comments FS MDPI 100/50 - Advair Diskus 100/50 mcg
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/25 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between FS MDPI 100/25 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0624
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 34.14
Confidence Interval (2-Sided) 95%
-1.8 to 70.1
Estimation Comments FS MDPI 100/25 mcg - Advair Diskus 100/50 mcg
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/12.5mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between FS MDPI 100/12.5 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8503
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 3.42
Confidence Interval (2-Sided) 95%
-32.3 to 39.1
Estimation Comments FS MDPI 100/12.5mcg - Advair Diskus 100/50 mcg
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/6.25 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between FS MDPI 100/6.25 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0229
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value -41.72
Confidence Interval (2-Sided) 95%
-77.6 to -5.8
Estimation Comments FS MDPI 100/6.25 mcg - Advair Diskus 100/50 mcg
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between Fp MDPI 100 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value -193.42
Confidence Interval (2-Sided) 95%
-229.5 to -157.4
Estimation Comments Fp MDPI 100 mcg - Advair Diskus 100/50 mcg
2.Secondary Outcome
Title Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment
Hide Description

The secondary efficacy variable was the change from period-specific baseline in FEV1 at 12 hours, calculated as FEV1 measured at 12 hours postdose after subtracting period-specific baseline FEV1 at each treatment period.

The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline.

Time Frame Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all subjects in the ITT population who received at least 1 dose of study drug and had at least 1 evaluable standardized baseline-adjusted FEV1 AUC0-12.
Arm/Group Title Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg
Hide Arm/Group Description:
Subjects inhaled a single dose of 100 mcg fluticasone propionate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
Overall Number of Participants Analyzed 67 67 68 67 68 66
Least Squares Mean (Standard Error)
Unit of Measure: mL
11.53  (29.058) 128.49  (29.109) 170.51  (28.990) 209.85  (29.127) 238.30  (28.988) 170.54  (29.230)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between each FS MDPI 100/50 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 226.77
Confidence Interval (2-Sided) 95%
172.4 to 281.1
Estimation Comments FS MDPI 100/50 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/25 mcg
Comments The estimated treatment difference from the ANCOVA model between each FS MDPI 100/25 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 198.32
Confidence Interval (2-Sided) 95%
143.7 to 252.9
Estimation Comments FS MDPI 100/25 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/12.5mcg
Comments The estimated treatment difference from the ANCOVA model between each FS MDPI 100/12.5 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 158.99
Confidence Interval (2-Sided) 95%
104.7 to 213.3
Estimation Comments FS MDPI 100/12.5 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, FS MDPI 100/6.25 mcg
Comments The estimated treatment difference from the ANCOVA model between each FS MDPI 100/6.25 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 116.96
Confidence Interval (2-Sided) 95%
62.4 to 171.6
Estimation Comments FS MDPI 100/6.25 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between each Advair Diskus 100/50 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 159.01
Confidence Interval (2-Sided) 95%
104.3 to 213.7
Estimation Comments Advair Diskus 100/50 mcg - Fp MDPI 100 mcg
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/50 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between each FS MDPI 100/50 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0150
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 67.76
Confidence Interval (2-Sided) 95%
13.3 to 122.2
Estimation Comments FS MDPI 100/50 mcg - Advair Diskus 100/50 mcg
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/25 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between each FS MDPI 100/25 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1578
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value 39.31
Confidence Interval (2-Sided) 95%
-15.3 to 94.0
Estimation Comments FS MDPI 100/25 mcg - Advair Diskus 100/50 mcg
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/12.5mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between each FS MDPI 100/12.5 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9993
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-54.4 to 54.4
Estimation Comments FS MDPI 100/12.5 mcg - Advair Diskus 100/50 mcg
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/6.25 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between each FS MDPI 100/6.25 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1311
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value -42.05
Confidence Interval (2-Sided) 95%
-96.7 to 12.6
Estimation Comments FS MDPI 100/6.25 mcg - Advair Diskus 100/50 mcg
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Fp MDPI 100 mcg, Advair Diskus 100/50 mcg
Comments The estimated treatment difference from the ANCOVA model between each Fp MDPI 100 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significance of 0.05 or alpha of 0.05.
Method ANCOVA
Comments Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1.
Method of Estimation Estimation Parameter LSM difference
Estimated Value -159.01
Confidence Interval (2-Sided) 95%
-213.7 to -104.3
Estimation Comments Fp MDPI 100 mcg - Advair Diskus 100/50 mcg
3.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol
Hide Description Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. The primary pharmacokinetic parameters were AUC0-t and Cmax for Salmeterol.
Time Frame Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience.
Arm/Group Title Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg
Hide Arm/Group Description:
Subjects inhaled a single dose of 100 mcg fluticasone propionate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
Overall Number of Participants Analyzed 0 62 65 61 61 62
Mean (Standard Deviation)
Unit of Measure: pg*hr/mL
32.8  (20.98) 69.9  (35.36) 133.5  (63.13) 309.3  (143.43) 173.5  (106.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/50 mcg, Advair Diskus 100/50 mcg
Comments The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=58
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter geometric mean ratio
Estimated Value 1.929
Confidence Interval (2-Sided) 90%
1.690 to 2.202
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/25 mcg, Advair Diskus 100/50 mcg
Comments The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=59
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter geometric mean ratio
Estimated Value 0.800
Confidence Interval (2-Sided) 90%
0.702 to 0.911
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/12.5mcg, Advair Diskus 100/50 mcg
Comments The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=61
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter geometric mean ratio
Estimated Value 0.427
Confidence Interval (2-Sided) 90%
0.376 to 0.485
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/6.25 mcg, Advair Diskus 100/50 mcg
Comments The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=59
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.172
Confidence Interval (2-Sided) 90%
0.151 to 0.196
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Salmeterol
Hide Description Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. The primary pharmacokinetic parameters were AUC0-t and Cmax for Salmeterol.
Time Frame Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience.
Arm/Group Title Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg
Hide Arm/Group Description:
Subjects inhaled a single dose of 100 mcg fluticasone propionate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
Overall Number of Participants Analyzed 0 62 65 61 61 62
Mean (Standard Deviation)
Unit of Measure: pg/mL
16.0  (8.86) 35.8  (20.25) 67.5  (34.71) 154.5  (80.28) 42.3  (19.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/50 mcg, Advair Diskus 100/50 mcg
Comments The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=58
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter geometric mean ratio
Estimated Value 3.622
Confidence Interval (2-Sided) 90%
3.149 to 4.168
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/25 mcg, Advair Diskus 100/50 mcg
Comments The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=59
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter geometric mean ratio
Estimated Value 1.534
Confidence Interval (2-Sided) 90%
1.335 to 1.763
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/12.5mcg, Advair Diskus 100/50 mcg
Comments The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=61
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter geometric mean ratio
Estimated Value 0.795
Confidence Interval (2-Sided) 90%
0.694 to 0.911
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FS MDPI 100/6.25 mcg, Advair Diskus 100/50 mcg
Comments The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=59
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter geometric mean ratio
Estimated Value 0.339
Confidence Interval (2-Sided) 90%
0.295 to 0.390
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol
Hide Description Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived.
Time Frame Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience.
Arm/Group Title Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg
Hide Arm/Group Description:
Subjects inhaled a single dose of 100 mcg fluticasone propionate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
Overall Number of Participants Analyzed 0 62 65 61 61 62
Median (Full Range)
Unit of Measure: hours
0.1
(0.1 to 12.1)
0.1
(0.1 to 2.0)
0.1
(0.1 to 2.0)
0.1
(0.1 to 1.5)
0.5
(0.1 to 2.0)
6.Secondary Outcome
Title Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period
Hide Description

TEAEs were recorded during each double-blind treatment. In addition, at the end of each treatment, patients continued to use 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily, so adverse events during this treatment were assigned to Fp MDPI 50 mcg.

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 in

Time Frame Day 1 up to Day 35
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg Fp MDPI 50 mcg X 2 BID
Hide Arm/Group Description:
Subjects inhaled a single dose of 100 mcg fluticasone propionate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
Patients used 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily during the 'washout' between treatment periods, so adverse events during this treatment were assigned to Fp MDPI 50 mcg.
Overall Number of Participants Analyzed 67 68 69 67 68 66 72
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse event
2
   3.0%
2
   2.9%
3
   4.3%
1
   1.5%
1
   1.5%
3
   4.5%
17
  23.6%
Severe adverse event
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.5%
0
   0.0%
1
   1.4%
Treatment-related adverse event
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
0
   0.0%
1
   1.5%
1
   1.4%
Deaths
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Other serious adverse events
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Withdrawn from treatment due to AE
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
Time Frame Day 1 to Day 35
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg Fp MDPI 50 mcg X 2 BID
Hide Arm/Group Description Subjects inhaled a single dose of 100 mcg fluticasone propionate. Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate. Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate. Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate. Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms. Patients used 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily during the 'washout' between treatment periods, so adverse events during this treatment were assigned to Fp MDPI 50 mcg.
All-Cause Mortality
Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg Fp MDPI 50 mcg X 2 BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/68 (0.00%)   0/69 (0.00%)   0/67 (0.00%)   0/68 (0.00%)   0/66 (0.00%)   0/72 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg Fp MDPI 50 mcg X 2 BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/68 (0.00%)   0/69 (0.00%)   0/67 (0.00%)   0/68 (0.00%)   0/66 (0.00%)   0/72 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Fp MDPI 100 mcg FS MDPI 100/6.25 mcg FS MDPI 100/12.5mcg FS MDPI 100/25 mcg FS MDPI 100/50 mcg Advair Diskus 100/50 mcg Fp MDPI 50 mcg X 2 BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/68 (0.00%)   0/69 (0.00%)   0/67 (0.00%)   0/68 (0.00%)   0/66 (0.00%)   4/72 (5.56%) 
Respiratory, thoracic and mediastinal disorders               
Upper respiratory tract infection  1  0/67 (0.00%)  0/68 (0.00%)  0/69 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  0/66 (0.00%)  4/72 (5.56%) 
1
Term from vocabulary, MedDRA (15.1)
Indicates events were collected by systematic assessment
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: 1-215-591-3000
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT01772368     History of Changes
Other Study ID Numbers: FSS-AS-201
First Submitted: January 17, 2013
First Posted: January 21, 2013
Results First Submitted: February 28, 2017
Results First Posted: April 12, 2017
Last Update Posted: June 12, 2017