Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Conducted at 9 US sites from May-October 2011. Entire period of study participation per subject was a maximum of 15 weeks. Planned target enrollment of 84 subjects.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This was a chronic dosing study (7 days), 3-period, 6-treatment, incomplete block, crossover study. Each subject received 3 of 6 possible treatments; each treatment period was separated by a washout period 7-28 days. By-treatment sequence tabulations of the data were not pre-specified.

Reporting Groups

  Description
All Subjects Randomized

Participant Flow:   Overall Study

  All Subjects Randomized
 STARTED  103
 GP MDI 36 µg BID  49[1]
 GP MDI 18 µg BID  49
 GP MDI 9 µg BID  49
 GP MDI 4.6 µg BID  45
 Placebo MDI BID  48
 Atrovent HFA 34 µg BID  48
 COMPLETED  89
 NOT COMPLETED  14
  Withdrawal by Subject   3
  Protocol discontinuation criteria   8
  Physician Decision   1
  Lost to Follow-up   2
[1] Glycopyrronium Metered Dose Inhaler

Baseline Characteristics

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

Reporting Groups

Description
ITT Population ITT Population includes all subjects who were randomized, received at least 1 dose of study treatment, and had both baseline and post-baseline efficacy data for that treatment.

Baseline Measures

  ITT Population
Number of Participants
[units: Participants] 		103
Age Continuous
[units: years]
Mean ± Standard Deviation		 61.2 ± 8.19
Gender, Male/Female
[units: Participants]
 
Female 48
Male 55

Outcome Measures

1. Primary Outcome Measure: FEV1 AUC0-12   [ Time Frame: Day 7 ( -1 hour, -30 min, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 5.5 hours, 6.5 hours, 8 hours, 10 hours, 11.5 hours, and 12 hours) ]

Measure Type Primary
Measure Name FEV1 AUC0-12
Measure Description FEV1 AUC0-12 following chronic dosing (1 week), normalized.
Time Frame Day 7 ( -1 hour, -30 min, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 5.5 hours, 6.5 hours, 8 hours, 10 hours, 11.5 hours, and 12 hours)
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Modified Intent to Treat (MITT) Population includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 40 41 41 39 42 40
FEV1 AUC0-12
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		1.477 (1.418 to 1.537) 1.497 (1.437 to 1.556) 1.443 (1.385 to 1.501) 1.514 (1.456 to 1.572) 1.465 (1.405 to 1.524) 1.323 (1.263 to 1.382)

No statistical analysis provided for FEV1 AUC0-12

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

Measure Type Secondary
Measure Name Peak change from baseline in FEV1 on Day 1
Measure Description Highest value of FEV1 post-dose minus baseline on Day 1 (baseline-adjusted)
Time Frame Day 1
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
MITT Population includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 45 46 44 41 44 46
Peak change from baseline in FEV1 on Day 1
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.245 (0.195 to 0.295) 0.221 (0.172 to 0.270) 0.181 (0.130 to 0.232) 0.204 (0.153 to 0.255) 0.250 (0.198 to 0.301) 0.071 (0.021 to 0.120)

No statistical analysis provided for Peak change from baseline in FEV1 on Day 1

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 hour, 2 hours) ]

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)
Time Frame Day 1 (15 min, 30 min, 1 hour, 2 hours)
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
MITT Population includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 44 45 43 40 44 45
Time to onset of action ( ≥10% improvement in FEV1) on Day 1
[units: % of subjects]
            
15 minutes 32 31 19 25 48 7
30 minutes 32 18 7 20 25 9
1 hour 5 11 23 8 9 4
2 hours 2 13 14 15 2 13
No onset within 2 hours 30 27 37 33 16 67

No statistical analysis provided for Time to onset of action ( ≥10% improvement in FEV1) on Day 1

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

Measure Type Secondary
Measure Name Proportion of subjects achieving at least 12% improvement in FEV1 on Day 1
Measure Description Proportion of subjects achieving at least 12% improvement in FEV1 (relative to baseline)
Time Frame Day 1
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
MITT Population: This includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 45 46 44 41 45 46
Proportion of subjects achieving at least 12% improvement in FEV1 on Day 1
[units: Percent]
 66.67 58.70 52.27 60.98 77.78 17.39

No statistical analysis provided for Proportion of subjects achieving at least 12% improvement in FEV1 on Day 1

5. Secondary Outcome Measure: Peak change from baseline in IC on Day 1   [ Time Frame: Day 1 ]

Measure Type Secondary
Measure Name Peak change from baseline in IC on Day 1
Measure Description Peak change from baseline in Inspiratory Capacity (IC) on Day 1 (mean of 1 and 2 hours post-dose minus baseline on Day 1)
Time Frame Day 1
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
MITT Population includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 45 45 44 41 45 46
Peak change from baseline in IC on Day 1
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.240 (0.165 to 0.316) 0.276 (0.201 to 0.351) 0.185 (0.111 to 0.259) 0.187 (0.111 to 0.262) 0.252 (0.173 to 0.330) 0.040 (-0.036 to 0.117)

No statistical analysis provided for Peak change from baseline in IC on Day 1

6. Secondary Outcome Measure: Change from baseline in morning pre-dose FEV1 on Day 7   [ Time Frame: Day 7 ]

Measure Type Secondary
Measure Name Change from baseline in morning pre-dose FEV1 on Day 7
Measure Description Change from baseline in morning pre-dose FEV1
Time Frame Day 7
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
MITT Population includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 45 45 43 41 43 46
Change from baseline in morning pre-dose FEV1 on Day 7
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.088 (0.039 to 0.136) 0.075 (0.027 to 0.124) 0.010 (-0.039 to 0.059) 0.084 (0.035 to 0.133) -0.088 (-0.138 to -0.037) -0.043 (-0.092 to 0.006)

No statistical analysis provided for Change from baseline in morning pre-dose FEV1 on Day 7

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

Measure Type Secondary
Measure Name Peak change from baseline in FEV1 on Day 7
Measure Description Peak change from baseline in FEV1
Time Frame Day 7
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
MITT Population includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 45 45 43 41 43 44
Peak change from baseline in FEV1 on Day 7
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.242 (0.181 to 0.302) 0.224 (0.164 to 0.284) 0.223 (0.162 to 0.285) 0.238 (0.176 to 0.300) 0.225 (0.164 to 0.287) 0.070 (0.009 to 0.131)

No statistical analysis provided for Peak change from baseline in FEV1 on Day 7

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

Measure Type Secondary
Measure Name Peak change from baseline in IC on Day 7
Measure Description Peak change from baseline in IC
Time Frame Day 7
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
MITT Population includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 45 45 43 41 43 44
Peak change from baseline in IC on Day 7
[units: Liters]
Least Squares Mean (95% Confidence Interval) 		0.213 (0.130 to 0.295) 0.189 (0.107 to 0.271) 0.161 (0.077 to 0.245) 0.192 (0.107 to 0.277) 0.191 (0.106 to 0.275) -0.029 (-0.112 to 0.055)

No statistical analysis provided for Peak change from baseline in IC on Day 7

9. Secondary Outcome Measure: Change from baseline in 12-hour post-dose trough FEV1 on Day 7   [ Time Frame: Day 7 ]

Measure Type Secondary
Measure Name Change from baseline in 12-hour post-dose trough FEV1 on Day 7
Measure Description Change from baseline in 12-hour post-dose trough FEV1
Time Frame Day 7
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
MITT Population includes subjects who completed at least 2 treatment periods, with minimally 1 pre-dose assessment on Day 7 for each of those 2 treatment periods with no protocol deviations believed to have a potential impact on efficacy results.

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo MDI BID Placebo MDI BID.

Measured Values

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo MDI BID
Number of Participants Analyzed
[units:participants]
 40 41 41 39 42 41
Change from baseline in 12-hour post-dose trough FEV1 on Day 7
[units: Liters]
Least Squares Mean (95% Confidence Interval) 		0.018 (-0.045 to 0.080) 0.079 (0.018 to 0.139) 0.004 (-0.057 to 0.065) 0.077 (0.016 to 0.139) -0.041 (-0.103 to 0.021) -0.054 (-0.117 to 0.009)

No statistical analysis provided for Change from baseline in 12-hour post-dose trough FEV1 on Day 7

Serious Adverse Events

Time Frame Adverse events were collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug.
Additional Description Safety population included all participants who received at least one dose of investigational drug and had safety data available; participants were included in safety population according to the investigational drug received

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo BID Placebo BID.

Serious Adverse Events

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo BID
Total, serious adverse events            
# participants affected / at risk 0/49 (0.00%) 0/49 (0.00%) 0/49 (0.00%) 1/45 (2.22%) 1/48 (2.08%) 0/48 (0.00%)
Respiratory, thoracic and mediastinal disorders            
COPD Exacerbation1, †            
# participants affected / at risk 0/49 (0.00%) 0/49 (0.00%) 0/49 (0.00%) 1/45 (2.22%) 0/48 (0.00%) 0/48 (0.00%)
# events 0 0 0 1 0 0
Vascular disorders            
Deep Vein Thrombosis1            
# participants affected / at risk 0/49 (0.00%) 0/49 (0.00%) 0/49 (0.00%) 0/45 (0.00%) 1/48 (2.08%) 0/48 (0.00%)
# events 0 0 0 0 1 0
† Events were collected by systematic assessment
1 Term from vocabulary,  MedDRA

Other Adverse Events

Time Frame Adverse events were collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug.
Additional Description Safety population included all participants who received at least one dose of investigational drug and had safety data available; participants were included in safety population according to the investigational drug received

Frequency Threshold

Threshold above which other adverse events are reported 5%

Reporting Groups

  Description
PT001 MDI 36 µg BID PT001 MDI 36 µg BID.
PT001 MDI 18 µg BID PT001 MDI 18 µg BID.
PT001 MDI 9 µg BID PT001 MDI 9 µg BID
PT001 MDI 4.6 µg BID PT001 MDI 4.6 µg BID.
Ipratropium Bromide HFA Inhalation Aerosol Ipratropium Bromide HFA Inhalation Aerosol 34 µg QID.
Placebo BID Placebo BID.

Other Adverse Events

  PT001 MDI 36 µg BID PT001 MDI 18 µg BID PT001 MDI 9 µg BID PT001 MDI 4.6 µg BID Ipratropium Bromide HFA Inhalation Aerosol Placebo BID
Total, other (not including serious) adverse events            
# participants affected / at risk 1/49 (2.04%) 2/49 (4.08%) 4/49 (8.16%) 4/45 (8.89%) 3/48 (6.25%) 1/48 (2.08%)
Gastrointestinal disorders            
Dry Mouth1, †            
# participants affected / at risk 1/49 (2.04%) 2/49 (4.08%) 4/49 (8.16%) 4/45 (8.89%) 3/48 (6.25%) 1/48 (2.08%)
# events 1 2 4 4 3 1
† 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]
.