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A Dose-Range Finding Study of SUN-101 in Subjects With Moderate to Severe COPD (GOLDEN 6)

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: NCT02038829
Recruitment Status : Completed
First Posted : January 17, 2014
Results First Posted : January 25, 2018
Last Update Posted : April 10, 2018
Sponsor:
Information provided by (Responsible Party):
Sunovion Respiratory Development Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition COPD
Interventions Drug: Placebo
Drug: SUN101 3 mcg
Drug: SUN-101 6.25 mcg
Drug: SUN-101 12.5 mcg
Drug: SUN-101 50 mcg
Drug: Aclidinium
Enrollment 96
Recruitment Details  
Pre-assignment Details Eligible subjects will be randomized to one of 12 treatment sequences. There will be a minimum of a 7-day washout period between each treatment visit. At each visit, subjects will receive one dose of study medication according to the sequence assigned.
Arm/Group Title Treatment Group 1 Treatment Group 2 Treatment Group 3 Treatment Group 4 Treatment Group 5 Treatment Group 6 Treatment Group 7 Treatment Group 8 Treatment Group 9 Treatment Group 10 Treatment Group 11 Treatment Group 12
Hide Arm/Group Description Participants received SUN-101 50mcg; Aclidinium 400mcg; Placebo; SUN-101 6,25mcg; SUN-101 3mcg; SUN-101 12.5mcg Participants received Placebo; SUN-101 50mcg; SUN-101 3mcg Aclidinium 400mcg; SUN-101 12.5 mcg; SUN-101 6mcg Participants received SUN-101 3mcg Placebo; SUN-101 12.5 mcg; SUN-101 50mcg; SUN-101 6.25mcg Aclidinium 400mcg; Participants received SUN-101 12.5 mcg; SUN-101 3mcg Placebo; SUN-101 50mcg; Aclidinium 400mcg; SUN-101 6.25mcg

Participants received SUN-101 6.25mcg SUN-101 12.5 mcg; Aclidinium 400mcg; SUN-101 3mcg SUN-101 50mcg Placebo;

Aclidinium 400mcg; SUN-101 6.25mcg

Participants received Aclidinium 400mcg; SUN-101 6.25mcg SUN-101 50mcg SUN-101 12.5 mcg; Placebo; SUN-101 3mcg

Placebo;

Participants received SUN-101 3mcg SUN-101 50mcg Aclidinium 400mcg; Placebo; SUN-101 6.25mcg SUN-101 12.5 mcg;

SUN-101 3mcg

Participants received Aclidinium 400mcg; SUN-101 3mcg SUN-101 6.25mcg SUN-101 50mcg SUN-101 12.5 mcg; Placebo; Participants received SUN-101 6.25mcg Aclidinium 400mcg; SUN-101 12.5 mcg SUN-101 3mcg Placebo; SUN-101 50mcg Participants received SUN-101 12.5 mcg SUN-101 6.25mcg Placebo; Aclidinium 400mcg; SUN-101 50 mcg SUN-101 3mcg Participants received Placebo; SUN-101 12.5 mcg SUN-101 50 mcg SUN-101 6.25mcg Aclidinium 400mcg; SUN-101 3mcg Participants received SUN-101 50 mcg Placebo; SUN-101 3mcg SUN-101 6.25mcg Aclidinium 400mcg; SUN-101 12.5 mcg
Period Title: Treatment Period 1
Started 8 8 8 8 8 8 8 8 8 8 8 8
Completed 8 8 8 8 8 8 8 8 8 8 8 8
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 1
Started 8 8 8 8 8 8 8 8 8 8 8 8
Completed 8 8 8 8 7 8 8 8 8 8 8 8
Not Completed 0 0 0 0 1 0 0 0 0 0 0 0
Reason Not Completed
Death             0             0             0             0             1             0             0             0             0             0             0             0
Period Title: Treatment Period 2
Started 8 8 8 8 7 8 8 8 8 8 8 8
Completed 7 8 8 8 7 8 8 8 8 8 7 8
Not Completed 1 0 0 0 0 0 0 0 0 0 1 0
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             0             0             1             0
Withdrawal by Subject             1             0             0             0             0             0             0             0             0             0             0             0
Period Title: Washout Period 2
Started 7 8 8 8 7 8 8 8 8 8 7 8
Completed 7 8 8 8 7 7 8 8 7 8 7 8
Not Completed 0 0 0 0 0 1 0 0 1 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             1             0             0             0
Withdrawal by Subject             0             0             0             0             0             1             0             0             0             0             0             0
Period Title: Treatment Period 3
Started 7 8 8 8 7 7 8 8 7 8 7 8
Completed 7 8 8 8 7 7 8 8 7 8 7 8
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 3
Started 7 8 8 8 7 7 8 8 7 8 7 8
Completed 7 8 8 8 7 7 8 8 7 8 7 8
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Treatment Period 4
Started 7 8 8 8 7 7 8 8 7 8 7 8
Completed 7 7 8 8 7 7 8 8 7 8 7 8
Not Completed 0 1 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             1             0             0             0             0             0             0             0             0             0             0
Period Title: Washout Period 4
Started 7 7 8 8 7 7 8 8 7 8 7 8
Completed 7 7 8 8 7 7 7 8 7 8 7 8
Not Completed 0 0 0 0 0 0 1 0 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             0             1             0             0             0             0             0
Period Title: Treatment Period 5
Started 7 7 8 8 7 7 7 8 7 8 7 8
Completed 7 7 8 8 7 7 7 8 7 8 7 8
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 5
Started 7 7 8 8 7 7 7 8 7 8 7 8
Completed 7 7 8 8 7 7 7 8 7 8 7 8
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Treatment Period 6
Started 7 7 8 8 7 7 7 8 7 8 7 8
Completed 7 7 7 8 7 7 7 8 7 8 7 8
Not Completed 0 0 1 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             0             1             0             0             0             0             0             0             0             0             0
Arm/Group Title Total
Hide Arm/Group Description Total of all participants
Overall Number of Baseline Participants 96
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants
<=18 years
0
   0.0%
Between 18 and 65 years
94
  97.9%
>=65 years
2
   2.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 96 participants
54.6  (5.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants
Female
50
  52.1%
Male
46
  47.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
96
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
10
  10.4%
White
86
  89.6%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 96 participants
96
1.Primary Outcome
Title Change From Baseline in Trough FEV1 at Treatment Visit Day 7 Compared to Placebo.
Hide Description Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the average of the 2 spirometry values collected at 23 hours 15 minutes, and 23 hours 45 minutes post-morning dose on Day 7 of each Treatment Period. The FEV1 values within 6 hours after the use of rescue medication were considered as missing. Baseline was calculated as the mean of the FEV1 values at 45 minutes and 15 minutes prior to the morning dose at Day 1 of each Treatment Period
Time Frame Baseline and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all subjects who were randomized to treatment, received at least one dose of study medication, and had at least one trough FEV1 evaluation and the corresponding baseline FEV1 for at least one treatment period.
Arm/Group Title Placebo SUN-101 3 mcg SUN-101 6.25 mcg SUN-101 12.5 mcg SUN-101 50 mcg Aclidinium 400 mcg
Hide Arm/Group Description:

Placebo bid

Placebo: Placebo

SUN-101 3 mcg bid

SUN101 3 mcg: SUN-101 3 mcg bid

SUN-101 6.25 mcg bid

SUN-101 6.25 mcg: SUN-101 6.25 mcg bid

SUN-101 12.5 mcg bid

SUN-101 12.5 mcg: SUN-101 12.5 mcg bid

SUN-101 50 mcg bid

SUN-101 50 mcg: SUN-101 50 mcg bid

Aclidinium 400 mcg bid

Aclidinium: Aclidinium 400 mcg bid

Overall Number of Participants Analyzed 92 91 92 90 92 94
Least Squares Mean (Standard Error)
Unit of Measure: liters
-0.0282  (0.0300) -0.0156  (0.0300) 0.0540  (0.0238) 0.0806  (0.0300) 0.1092  (0.0300) 0.1285  (0.0300)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SUN-101 3 mcg
Comments An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Superiority
Comments A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value 0.9730
Comments P-values were adjusted using Dunnett’s method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity.
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.0126
Confidence Interval (2-Sided) 95%
-0.0318 to 0.0569
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0225
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, SUN-101 6.25 mcg
Comments An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Superiority
Comments A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value 0.0014
Comments P-values were adjusted using Dunnett’s method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity.
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.0822
Confidence Interval (2-Sided) 95%
0.0380 to 0.1264
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0225
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, SUN-101 12.5 mcg
Comments An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Superiority
Comments A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value <0.0001
Comments P-values were adjusted using Dunnett’s method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity.
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.1088
Confidence Interval (2-Sided) 95%
0.0644 to 0.1532
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0226
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, SUN-101 50 mcg
Comments An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation
Type of Statistical Test Superiority
Comments A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value <0.0001
Comments P-values were adjusted using Dunnett’s method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity.
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.1375
Confidence Interval (2-Sided) 95%
0.0931 to 0.1818
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0226
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Aclidinium 400 mcg
Comments An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Superiority
Comments A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value <0.0001
Comments P-values were adjusted using Dunnett’s method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity.
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.1567
Confidence Interval (2-Sided) 95%
0.1121 to 0.2012
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0226
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Standardized Change From Baseline in FEV1 AUC(0-12hours)
Hide Description The standardized FEV1 AUC(0-12) on Day 7 was calculated using the trapezoidal rule from the changes in FEV1 from the baseline value (the mean of the two FEV1 values at 45 minutes and 15 minutes prior to morning dose at Day 1 of the respective Treatment Periods) and dividing by the actual length of the time interval).
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all subjects who were randomized to treatment, received at least one dose of study medication, and had at least one trough FEV1 evaluation and the corresponding baseline FEV1 for at least one treatment period.
Arm/Group Title Placebo SUN-101 3 mcg SUN-101 6.25 mcg SUN-101 12.5 mcg SUN-101 50 mcg Aclidinium 400 mcg
Hide Arm/Group Description:

Placebo bid

Placebo: Placebo

SUN-101 3 mcg bid

SUN101 3 mcg: SUN-101 3 mcg bid

SUN-101 6.25 mcg bid

SUN-101 6.25 mcg: SUN-101 6.25 mcg bid

SUN-101 12.5 mcg bid

SUN-101 12.5 mcg: SUN-101 12.5 mcg bid

SUN-101 50 mcg bid

SUN-101 50 mcg: SUN-101 50 mcg bid

Aclidinium 400 mcg bid

Aclidinium: Aclidinium 400 mcg bid

Overall Number of Participants Analyzed 92 91 92 90 92 94
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.0203  (0.0315) 0.0323  (0.0316) 0.0639  (0.0315) 0.1052  (0.0316) 0.1760  (0.0315) 0.1699  (0.0316)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SUN-101 3 mcg
Comments An mixed effects model was used with standardized FEV1 AUC(0-12) on Day 7 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Superiority
Comments A sample size of 78 subjects (rounding to 84 for using Williams squares) provides ~80% power to detect a 55 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in AUC(0-12) of 143 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value 0.0046
Comments [Not Specified]
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.0526
Confidence Interval (2-Sided) 95%
0.0163 to 0.0888
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0184
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, SUN-101 6.25 mcg
Comments An mixed effects model was used with standardized FEV1 AUC(0-12) on Day 7 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Superiority
Comments A sample size of 78 subjects (rounding to 84 for using Williams squares) provides ~80% power to detect a 55 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in AUC(0-12) of 143 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.0842
Confidence Interval (2-Sided) 95%
0.0478 to 0.1206
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0185
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, SUN-101 12.5 mcg
Comments An mixed effects model was used with standardized FEV1 AUC(0-12) on Day 7 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Non-Inferiority
Comments A sample size of 78 subjects (rounding to 84 for using Williams squares) provides ~80% power to detect a 55 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in AUC(0-12) of 143 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.1255
Confidence Interval (2-Sided) 95%
0.0890 to 0.1621
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0186
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, SUN-101 50 mcg
Comments An mixed effects model was used with standardized FEV1 AUC(0-12) on Day 7 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Superiority
Comments A sample size of 78 subjects (rounding to 84 for using Williams squares) provides ~80% power to detect a 55 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in AUC(0-12) of 143 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.1963
Confidence Interval (2-Sided) 95%
0.1601 to 0.2325
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0184
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Aclidinium 400 mcg
Comments An mixed effects model was used with standardized FEV1 AUC(0-12) on Day 7 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation.
Type of Statistical Test Superiority
Comments A sample size of 78 subjects (rounding to 84 for using Williams squares) provides ~80% power to detect a 55 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in AUC(0-12) of 143 and a within-subject correlation of 0.3.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method LS Mean (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean (SE)
Estimated Value 0.1902
Confidence Interval (2-Sided) 95%
0.1537 to 0.2268
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0186
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment)
Hide Description A treatment emergent adverse event (TEAE) is any TEAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any TEAE with both a missing start and stop date.
Time Frame Over 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
Arm/Group Title Placebo SUN-101 3 mcg SUN-101 6.25 mcg SUN-101 12.5 mcg SUN-101 50 mcg Aclidinium 400 mcg TOTAL
Hide Arm/Group Description:

Placebo bid

Placebo: Placebo

SUN-101 3 mcg bid

SUN101 3 mcg: SUN-101 3 mcg bid

SUN-101 6.25 mcg bid

SUN-101 6.25 mcg: SUN-101 6.25 mcg bid

SUN-101 12.5 mcg bid

SUN-101 12.5 mcg: SUN-101 12.5 mcg bid

SUN-101 50 mcg bid

SUN-101 50 mcg: SUN-101 50 mcg bid

Aclidinium 400 mcg bid

Aclidinium: Aclidinium 400 mcg bid

Total number of study participants
Overall Number of Participants Analyzed 92 91 92 90 92 94 96
Measure Type: Number
Unit of Measure: participants
11 22 23 24 14 24 62
4.Secondary Outcome
Title Percentage of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment)
Hide Description A treatment emergent adverse event (TEAE) is any TEAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any TEAE with both a missing start and stop date.
Time Frame Over 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication.
Arm/Group Title Placebo SUN-101 3 mcg SUN-101 6.25 mcg SUN-101 12.5 mcg SUN-101 50 mcg Aclidinium 400 mcg TOTAL
Hide Arm/Group Description:

Placebo bid

Placebo: Placebo

SUN-101 3 mcg bid

SUN101 3 mcg: SUN-101 3 mcg bid

SUN-101 6.25 mcg bid

SUN-101 6.25 mcg: SUN-101 6.25 mcg bid

SUN-101 12.5 mcg bid

SUN-101 12.5 mcg: SUN-101 12.5 mcg bid

SUN-101 50 mcg bid

SUN-101 50 mcg: SUN-101 50 mcg bid

Aclidinium 400 mcg bid

Aclidinium: Aclidinium 400 mcg bid

Total number of study participants
Overall Number of Participants Analyzed 92 91 92 90 92 94 96
Measure Type: Number
Unit of Measure: percentage of participants
12.0 24.2 25.0 26.7 15.2 25.5 64.6
Time Frame Over 7 days
Adverse Event Reporting Description A treatment emergent serious adverse event (TESAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date.
 
Arm/Group Title Placebo SUN-101 3 mcg SUN-101 6.25 mcg SUN-101 12.5 mcg SUN-101 50 mcg Aclidinium 400 mcg
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Placebo bid

Placebo: Placebo

SUN-101 3 mcg bid

SUN101 3 mcg: SUN-101 3 mcg bid

SUN-101 6.25 mcg bid

SUN-101 6.25 mcg: SUN-101 6.25 mcg bid

SUN-101 12.5 mcg bid

SUN-101 12.5 mcg: SUN-101 12.5 mcg bid

SUN-101 50 mcg bid

SUN-101 50 mcg: SUN-101 50 mcg bid

Aclidinium 400 mcg bid

Aclidinium: Aclidinium 400 mcg bid

All-Cause Mortality
Placebo SUN-101 3 mcg SUN-101 6.25 mcg SUN-101 12.5 mcg SUN-101 50 mcg Aclidinium 400 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo SUN-101 3 mcg SUN-101 6.25 mcg SUN-101 12.5 mcg SUN-101 50 mcg Aclidinium 400 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/92 (1.09%)      0/91 (0.00%)      2/92 (2.17%)      1/90 (1.11%)      0/92 (0.00%)      3/94 (3.19%)    
Cardiac disorders             
acute myocardial infarction  1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/92 (0.00%)  0 0/90 (0.00%)  0 0/92 (0.00%)  0 1/94 (1.06%)  1
atrial fibrillation  1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/92 (0.00%)  0 0/90 (0.00%)  0 0/92 (0.00%)  0 1/94 (1.06%)  1
cardia failure acute  1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/92 (0.00%)  0 0/90 (0.00%)  0 0/92 (0.00%)  0 1/94 (1.06%)  1
General disorders             
chest pain  1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/92 (0.00%)  0 0/90 (0.00%)  0 0/92 (0.00%)  0 1/94 (1.06%)  1
Infections and infestations             
bronchitis  1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/92 (0.00%)  0 0/90 (0.00%)  0 0/92 (0.00%)  0 1/94 (1.06%)  1
metapneumovirus infection  1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/92 (0.00%)  0 0/90 (0.00%)  0 0/92 (0.00%)  0 0/94 (0.00%)  0
Injury, poisoning and procedural complications             
Toxicity to various agents  1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/92 (1.09%)  1 0/90 (0.00%)  0 0/92 (0.00%)  0 0/94 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
chronic obstructive pulmonary disease  1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/92 (1.09%)  1 1/90 (1.11%)  1 0/92 (0.00%)  1/94 (1.06%)  1
pleural effusion  1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/92 (0.00%)  0 0/90 (0.00%)  0 0/92 (0.00%)  0 1/94 (1.06%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo SUN-101 3 mcg SUN-101 6.25 mcg SUN-101 12.5 mcg SUN-101 50 mcg Aclidinium 400 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/92 (2.17%)      6/91 (6.59%)      4/92 (4.35%)      6/90 (6.67%)      5/92 (5.43%)      10/94 (10.64%)    
Nervous system disorders             
Dysgeusia  1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/92 (1.09%)  1 0/90 (0.00%)  0 1/92 (1.09%)  1 8/94 (8.51%)  8
Respiratory, thoracic and mediastinal disorders             
cough  1  2/92 (2.17%)  2 6/91 (6.59%)  6 3/92 (3.26%)  3 6/90 (6.67%)  6 4/92 (4.35%)  4 2/94 (2.13%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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.
In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Respiratory Medical Director
Organization: Sunovion Pharmaceuticals Inc.
Phone: 1-866-503-6351
Layout table for additonal information
Responsible Party: Sunovion Respiratory Development Inc.
ClinicalTrials.gov Identifier: NCT02038829     History of Changes
Other Study ID Numbers: SUN101-201
First Submitted: January 15, 2014
First Posted: January 17, 2014
Results First Submitted: January 2, 2018
Results First Posted: January 25, 2018
Last Update Posted: April 10, 2018