Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 10 sites in the US from April 2012 to August 2012. Study participation maximum of 26 weeks.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A randomized, double-blind,chronic dosing, four-period, eight-treatment, placebo-controlled, incomplete block, crossover, multicenter study.

Reporting Groups

  Description
All Subjects

Participant Flow:   Overall Study

  All Subjects
 STARTED  140
 GP MDI 18 µg BID  64
 GP MDI 9 µg BID  64
 GP MDI 4.6 µg BID  62
 GP MDI 2.4 µg BID  64
 GP MDI 1.2 µg BID  57
 GP MDI 0.6 µg BID  59
 Placebo MDI  62
 Spiriva® Handihaler®  62
 COMPLETED  110
 NOT COMPLETED  30
  Protocol specified criteria   4
  Protocol Violation   4
  Withdrawal by Subject   9
  Administrative reason   1
  Adverse Event   10
  Physician Decision   2

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.
Intent to Treat (ITT) Population: Subjects who randomized and received at least 1 dose of study drug, and had both baseline and post-baseline efficacy data for that treatment.

Reporting Groups

Description
All Subjects All Subjects

Baseline Measures

  All Subjects
Number of Participants
[units: Participants] 		140
Age Continuous
[units: Years]
Mean ± Standard Deviation
Gender, Male/Female
[units: ]
 
Female 65
Male 75

Outcome Measures

1. Primary Outcome Measure: FEV1 AUC0-12   [ Time Frame: Day 14 (-1 hr, -30 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 11.5 hr, 12 hr) ]

Measure Type Primary
Measure Name FEV1 AUC0-12
Measure Description Forced expiratory volume in 1 second (FEV1) normalized area under the curve 0-12 hours (AUC0-12) following chronic dosing for 14 days.
Time Frame Day 14 (-1 hr, -30 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 11.5 hr, 12 hr)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

2. Secondary Outcome Measure: Peak change from baseline in FEV1   [ Time Frame: Day 1 ]

Measure Type Secondary
Measure Name Peak change from baseline in FEV1
Measure Description Highest value of FEV1 post dose on day 1
Time Frame Day 1
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

3. Secondary Outcome Measure: Time to Onset of Action (>10% Improvement in FEV1) on Day 1   [ Time Frame: Day 1 (15 min, 30 min, 1 hr, 2 hrs, no onset within 2 hrs) ]

Measure Type Secondary
Measure Name Time to Onset of Action (>10% Improvement in FEV1) on Day 1
Measure Description Time to Onset of Action (>10% Improvement in FEV1) on Day 1.
Time Frame Day 1 (15 min, 30 min, 1 hr, 2 hrs, no onset within 2 hrs)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

4. Secondary Outcome Measure: Percentage of subjects achieving at least 12% improvement in FEV1   [ Time Frame: Day 1 ]

Measure Type Secondary
Measure Name Percentage of subjects achieving at least 12% improvement in FEV1
Measure Description Percentage of subjects achieving at least 12% improvement in FEV1.
Time Frame Day 1
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

5. Secondary Outcome Measure: Peak change from baseline in Inspiratory Capacity (IC)   [ Time Frame: Day 1 (1 hr and 2 hr post-dose ) ]

Measure Type Secondary
Measure Name Peak change from baseline in Inspiratory Capacity (IC)
Measure Description Peak change in Inspiratory Capacity (IC) mean of 1 and 2 hour post-dose assessments minus the baseline
Time Frame Day 1 (1 hr and 2 hr post-dose )
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

6. Secondary Outcome Measure: Change from baseline in morning pre-dose trough FEV1   [ Time Frame: Day 7 (average of the 60 and 30-minute pre-dose values on Treatment Day 7 minus the baseline) ]

Measure Type Secondary
Measure Name Change from baseline in morning pre-dose trough FEV1
Measure Description Change from baseline in morning pre-dose trough FEV1 (average of the 60 and 30-minute pre-dose values on Treatment Day 7 minus the baseline)
Time Frame Day 7 (average of the 60 and 30-minute pre-dose values on Treatment Day 7 minus the baseline)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

7. Secondary Outcome Measure: Peak change from baseline in FEV1   [ Time Frame: Day 7 ]

Measure Type Secondary
Measure Name Peak change from baseline in FEV1
Measure Description Peak change from baseline in FEV1 (defined as the change at the highest value of FEV1 post-dose minus the baseline)
Time Frame Day 7
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

8. Secondary Outcome Measure: Change from baseline in morning pre-dose trough Inspiratory Capacity (IC)   [ Time Frame: Day 7 ]

Measure Type Secondary
Measure Name Change from baseline in morning pre-dose trough Inspiratory Capacity (IC)
Measure Description Change from baseline in morning pre-dose trough IC (average of the 60 and 30-minute pre-dose assessments minus the baseline)
Time Frame Day 7
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

9. Secondary Outcome Measure: Peak change from baseline in IC   [ Time Frame: Day 7 (mean of 1 hr and 2 hr post-dose assessments) ]

Measure Type Secondary
Measure Name Peak change from baseline in IC
Measure Description Peak change from baseline in IC (mean of 1 hr and 2 hr post-dose assessments)
Time Frame Day 7 (mean of 1 hr and 2 hr post-dose assessments)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

10. Secondary Outcome Measure: Change from baseline in mean morning pre-dose daily PEFR   [ Time Frame: Day 7 (60 minutes pre-dose, 30 minutes pre-dose) ]

Measure Type Secondary
Measure Name Change from baseline in mean morning pre-dose daily PEFR
Measure Description Change from baseline in mean morning pre-dose daily PEFR (peak expiratory flow rate) taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (excluding reading taken pre-dose on Visit 2 [Treatment Day 1])
Time Frame Day 7 (60 minutes pre-dose, 30 minutes pre-dose)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

11. Secondary Outcome Measure: Change from baseline in morning post-dose daily PEFR   [ Time Frame: Day 7 (30 minutes post-dose) ]

Measure Type Secondary
Measure Name Change from baseline in morning post-dose daily PEFR
Measure Description Change from baseline in morning post-dose daily PEFR (peak expiratory flow rate) taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (excluding reading taken pre-dose on Visit 2 [Treatment Day 1])
Time Frame Day 7 (30 minutes post-dose)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

12. Secondary Outcome Measure: Change from baseline in mean evening pre-dose PEFR   [ Time Frame: Day 7 ]

Measure Type Secondary
Measure Name Change from baseline in mean evening pre-dose PEFR
Measure Description Change from baseline in mean evening pre-dose daily peak flow readings taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (subjects taking Spiriva performed a single evening assessment)
Time Frame Day 7
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

13. Secondary Outcome Measure: Change from baseline in mean evening post-dose PEFR   [ Time Frame: Day 7 ]

Measure Type Secondary
Measure Name Change from baseline in mean evening post-dose PEFR
Measure Description Change from baseline in mean evening post-dose daily peak flow readings taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (subjects taking Spiriva performed a single evening assessment)
Time Frame Day 7
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

14. Secondary Outcome Measure: Mean number of puffs of rescue medication   [ Time Frame: Day 7 ]

Measure Type Secondary
Measure Name Mean number of puffs of rescue medication
Measure Description Mean number of puffs of rescue medication recorded in subject diaries during each treatment period and by treatment and numbers of days treated
Time Frame Day 7
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

15. Secondary Outcome Measure: Change from baseline in morning pre-dose trough FEV1   [ Time Frame: Day 14 (average of the 60 and 30-minute pre-dose values on Treatment Day 14 minus the baseline) ]

Measure Type Secondary
Measure Name Change from baseline in morning pre-dose trough FEV1
Measure Description Change from baseline in morning pre-dose trough FEV1 (average of the 60 and 30-minute pre-dose values on Treatment Day 14 minus the baseline)
Time Frame Day 14 (average of the 60 and 30-minute pre-dose values on Treatment Day 14 minus the baseline)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

16. Secondary Outcome Measure: Peak change from baseline in FEV1   [ Time Frame: Day 14 ]

Measure Type Secondary
Measure Name Peak change from baseline in FEV1
Measure Description Peak change from baseline in FEV1 (defined as the change at the highest value of FEV1 post-dose minus the baseline)
Time Frame Day 14
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

17. Secondary Outcome Measure: Change from baseline for mean morning pre-dose trough IC   [ Time Frame: Day 14 (average of the 60 and 30-minute pre-dose assessments minus the baseline) ]

Measure Type Secondary
Measure Name Change from baseline for mean morning pre-dose trough IC
Measure Description Change from baseline for mean morning pre-dose trough IC (average of the 60 and 30-minute pre-dose assessments minus the baseline)
Time Frame Day 14 (average of the 60 and 30-minute pre-dose assessments minus the baseline)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

18. Secondary Outcome Measure: Peak change from baseline in IC   [ Time Frame: Day 14 (mean of 1 and 2 hour post-dose assessments minus the baseline) ]

Measure Type Secondary
Measure Name Peak change from baseline in IC
Measure Description Peak change from baseline in IC (mean of 1 and 2 hour post-dose assessments minus the baseline)
Time Frame Day 14 (mean of 1 and 2 hour post-dose assessments minus the baseline)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

19. Secondary Outcome Measure: Change from baseline in 12-hour post-dose trough FEV1   [ Time Frame: Day 14 (Baseline, 11.5 and 12 hours post dose) ]

Measure Type Secondary
Measure Name Change from baseline in 12-hour post-dose trough FEV1
Measure Description 12-hour post-dose trough FEV1 was defined as the mean of the FEV1 assessments taken at 11.5 and 12 hours post-dose minus the baseline
Time Frame Day 14 (Baseline, 11.5 and 12 hours post dose)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

20. Secondary Outcome Measure: Change from baseline in mean morning pre-dose daily PEFR   [ Time Frame: Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period before dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7) ]

Measure Type Secondary
Measure Name Change from baseline in mean morning pre-dose daily PEFR
Measure Description Change from baseline in mean morning pre-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (mean reading excluded reading taken pre-dose on Visit 2 [Treatment 1 Day 1]
Time Frame Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period before dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

21. Secondary Outcome Measure: Change from baseline in mean morning post-dose daily PEFR   [ Time Frame: Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period 30 minutes post dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7) ]

Measure Type Secondary
Measure Name Change from baseline in mean morning post-dose daily PEFR
Measure Description Change from baseline in mean morning post-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (mean reading excluded reading taken pre-dose on Visit 2 [Treatment 1 Day 1]
Time Frame Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period 30 minutes post dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

22. Secondary Outcome Measure: Change from baseline in mean evening pre-dose daily PEFR   [ Time Frame: Treatment Day 1 to the end of the 14-Day Treatment, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7) ]

Measure Type Secondary
Measure Name Change from baseline in mean evening pre-dose daily PEFR
Measure Description Change from baseline in mean evening pre-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (subjects taking Spiriva performed a single evening assessment)
Time Frame Treatment Day 1 to the end of the 14-Day Treatment, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

23. Secondary Outcome Measure: Change from baseline in mean evening post-dose daily PEFR   [ Time Frame: Through the end of the 14-Day Treatment ]

Measure Type Secondary
Measure Name Change from baseline in mean evening post-dose daily PEFR
Measure Description Change from baseline in mean evening post-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (subjects taking Spiriva performed a single evening assessment)
Time Frame Through the end of the 14-Day Treatment
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

24. Secondary Outcome Measure: Mean number of puffs of rescue medication (End of treatment)   [ Time Frame: Day 14 (End of treatment) ]

Measure Type Secondary
Measure Name Mean number of puffs of rescue medication (End of treatment)
Measure Description Mean number of puffs of rescue medication recorded in subject diaries during each treatment period and by treatment and numbers of days treated
Time Frame Day 14 (End of treatment)
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

25. Secondary Outcome Measure: Change from Baseline in Morning Pre-dose Trough FEV1 (mL) Averaging Treatment Day 7 and Day 14   [ Time Frame: Day 1 through Day 14 ]

Measure Type Secondary
Measure Name Change from Baseline in Morning Pre-dose Trough FEV1 (mL) Averaging Treatment Day 7 and Day 14
Measure Description Change from Baseline in Morning Pre-dose Trough FEV1 (mL) Averaging Treatment Day 7 and Day 14
Time Frame Day 1 through Day 14
Safety Issue?
Results not yet posted.  Anticipated Posting Date:   No text entered. Safety Issue:  No text entered.

Serious Adverse Events

Time Frame All of the adverse events (AEs) reported during the study were captured after signing informed consent through the 7-14 day follow up period.
Additional Description No text entered.

Reporting Groups

  Description
GP MDI 18 µg BID GP MDI 18 µg BID.
GP MDI 9 µg BID GP MDI 9 µg BID.
GP MDI 4.6 µg BID GP MDI 4.6 µg BID.
GP MDI 2.4 µg BID GP MDI 2.4 µg BID.
GP MDI 1.2 µg BID GP MDI 1.2 µg BID.
GP MDI 0.6 µg BID GP MDI 0.6 µg BID.
Placebo MDI Placebo MDI.
Spiriva 18 µg Spiriva 18 µg

Serious Adverse Events

  GP MDI 18 µg BID GP MDI 9 µg BID GP MDI 4.6 µg BID GP MDI 2.4 µg BID GP MDI 1.2 µg BID GP MDI 0.6 µg BID Placebo MDI Spiriva 18 µg
Total, serious adverse events                
# participants affected / at risk 0/64 (0.00%) 1/64 (1.56%) 0/62 (0.00%) 1/64 (1.56%) 0/57 (0.00%) 1/59 (1.69%) 1/62 (1.61%) 1/62 (1.61%)
Respiratory, thoracic and mediastinal disorders                
Chronic Obstructive Pulmonary Disease1, †                
# participants affected / at risk 0/64 (0.00%) 1/64 (1.56%) 0/62 (0.00%) 0/64 (0.00%) 0/57 (0.00%) 0/59 (0.00%) 1/62 (1.61%) 0/62 (0.00%)
# events 0 1 0 0 0 0 1 0
Cardiac disorders                
Acute myocardial infarction1, †                
# participants affected / at risk 0/64 (0.00%) 0/64 (0.00%) 0/62 (0.00%) 0/64 (0.00%) 0/57 (0.00%) 0/59 (0.00%) 0/62 (0.00%) 1/62 (1.61%)
# events 0 0 0 0 0 0 0 1
Infections and infestations                
Pneumonia1, †                
# participants affected / at risk 0/64 (0.00%) 0/64 (0.00%) 0/62 (0.00%) 1/64 (1.56%) 0/57 (0.00%) 0/59 (0.00%) 0/62 (0.00%) 0/62 (0.00%)
# events 0 0 0 1 0 0 0 0
Reproductive system and breast disorders                
Prostatitis1, †                
# participants affected / at risk 0/64 (0.00%) 0/64 (0.00%) 0/62 (0.00%) 0/64 (0.00%) 0/57 (0.00%) 1/59 (1.69%) 0/62 (0.00%) 0/62 (0.00%)
# events 0 0 0 0 0 1 0 0
† Events were collected by systematic assessment
1 Term from vocabulary,  MedDRA

Other Adverse Events

Time Frame All of the adverse events (AEs) reported during the study were captured after signing informed consent through the 7-14 day follow up period.
Additional Description No text entered.

Frequency Threshold

Threshold above which other adverse events are reported 5%

Reporting Groups

  Description
GP MDI 18 µg BID GP MDI 18 µg BID.
GP MDI 9 µg BID GP MDI 9 µg BID.
GP MDI 4.6 µg BID GP MDI 4.6 µg BID.
GP MDI 2.4 µg BID GP MDI 2.4 µg BID.
GP MDI 1.2 µg BID GP MDI 1.2 µg BID.
GP MDI 0.6 µg BID GP MDI 0.6 µg BID.
Placebo MDI Placebo MDI.
Spiriva 18 µg Spiriva 18 µg

Other Adverse Events

  GP MDI 18 µg BID GP MDI 9 µg BID GP MDI 4.6 µg BID GP MDI 2.4 µg BID GP MDI 1.2 µg BID GP MDI 0.6 µg BID Placebo MDI Spiriva 18 µg
Total, other (not including serious) adverse events                
# participants affected / at risk 2/64 (3.13%) 3/64 (4.69%) 3/62 (4.84%) 6/64 (9.38%) 3/57 (5.26%) 4/59 (6.78%) 3/62 (4.84%) 6/62 (9.68%)
Gastrointestinal disorders                
Dry mouth1, †                
# participants affected / at risk 2/64 (3.13%) 3/64 (4.69%) 3/62 (4.84%) 6/64 (9.38%) 3/57 (5.26%) 4/59 (6.78%) 3/62 (4.84%) 6/62 (9.68%)
# events 4 3 3 7 3 5 3 7
† Events were collected by systematic assessment
1 Term from vocabulary,  MedDRA

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title: Colin Reisner, MD, FCCP, FAAAAI
Organization: Pearl Therapeutics Inc
Phone 650-305-2600 
E-mail: [email protected]
.