Trial Outcomes & Findings for Chronic Dosing Cross-Over Study to Assess the Efficacy and Safety of Glycopyrronium (PT001) in Adult Subjects With Intermittent Asthma or Mild to Moderate Persistent Asthma (NCT NCT02433834)
NCT ID: NCT02433834
Last Updated: 2017-07-02
Results Overview
Forced Expiratory Volume in 1 second (FEV1) within 3 hours post-dosing on Day 15
COMPLETED
PHASE2
248 participants
From Day 1 to Within 3 hours post dosing on Day 15 in each of 5 treatment periods
2017-07-02
Participant Flow
Randomized, Double-Blind, Chronic-Dosing (14 days), 5-Period, 7-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multi-Center, Dose-Ranging Study to Assess the Efficacy and Safety of PT001 Relative to Placebo MDI and Open-Label Serevent® Diskus® Adult Subjects With Intermittent Asthma or Mild to Moderate Persistent Asthma
Eligible subjects were randomized to 1 of 24 pre-defined treatment sequences. There were 5 treatment periods lasting 14 days with a 7-14 day washout period in between and a follow-up phone call 7-14 days post final dose. By-sequence tabulations of the data were not pre-specified.
Participant milestones
| Measure |
Overall Study
All patients randomized
|
|---|---|
|
Overall Study
STARTED
|
248
|
|
Overall Study
GP MDI 28.8 µg
|
112
|
|
Overall Study
GP MDI 14.4 µg
|
230
|
|
Overall Study
GP MDI 7.2 µg
|
228
|
|
Overall Study
GP MDI 3.6 µg
|
118
|
|
Overall Study
GP MDI 1.9 µg
|
107
|
|
Overall Study
Placebo MDI
|
174
|
|
Overall Study
SAL 50 µg
|
167
|
|
Overall Study
COMPLETED
|
211
|
|
Overall Study
NOT COMPLETED
|
37
|
Reasons for withdrawal
| Measure |
Overall Study
All patients randomized
|
|---|---|
|
Overall Study
Protocol-specified criteria
|
7
|
|
Overall Study
Protocol Violation
|
3
|
|
Overall Study
Lost to Follow-up
|
6
|
|
Overall Study
Withdrawal by Subject
|
14
|
|
Overall Study
Adverse Event
|
6
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Chronic Dosing Cross-Over Study to Assess the Efficacy and Safety of Glycopyrronium (PT001) in Adult Subjects With Intermittent Asthma or Mild to Moderate Persistent Asthma
Baseline characteristics by cohort
| Measure |
Overall Study
n=222 Participants
All patients randomized
|
|---|---|
|
Age, Continuous
|
46.0 Years
STANDARD_DEVIATION 13.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
142 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
80 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Day 1 to Within 3 hours post dosing on Day 15 in each of 5 treatment periodsPopulation: Modified Intent-to-Treat (mITT) population was a subset of the Intent-to-Treat (ITT) Population and included all subjects who received treatment, had post-treatment efficacy data from at least two treatment periods, and did not hav e a major protocol violation that would preclude the use of data from these periods.
Forced Expiratory Volume in 1 second (FEV1) within 3 hours post-dosing on Day 15
Outcome measures
| Measure |
GP MDI 28.8 µg
n=101 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=212 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=202 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=109 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=99 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=158 Participants
Placebo MDI.
|
SAL 50 µg
n=155 Participants
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
Peak Change From Baseline in FEV1 Within 3 Hours Post-dosing on Day 15
|
0.284 Liter
Standard Error 0.0181
|
0.261 Liter
Standard Error 0.0141
|
0.252 Liter
Standard Error 0.0142
|
0.237 Liter
Standard Error 0.0176
|
0.215 Liter
Standard Error 0.0184
|
0.130 Liter
Standard Error 0.0154
|
0.285 Liter
Standard Error 0.0156
|
SECONDARY outcome
Timeframe: Day 1-Day 15 in each of 5 treatment periodsPopulation: Modified Intent-to-Treat (mITT) population was a subset of the Intent-to-Treat (ITT) Population and included all subjects who received treatment, had post-treatment efficacy data from at least two treatment periods, and did not hav e a major protocol violation that would preclude the use of data from these periods.
Change from baseline in morning pre-dose trough FEV1 on Day 15
Outcome measures
| Measure |
GP MDI 28.8 µg
n=101 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=212 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=204 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=109 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=99 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=159 Participants
Placebo MDI.
|
SAL 50 µg
n=155 Participants
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Morning Pre-dose Trough FEV1 on Day 15
|
0.073 Liter
Standard Error 0.0165
|
0.047 Liter
Standard Error 0.0116
|
0.042 Liter
Standard Error 0.0118
|
0.012 Liter
Standard Error 0.0159
|
0.018 Liter
Standard Error 0.0168
|
-0.012 Liter
Standard Error 0.0133
|
0.059 Liter
Standard Error 0.0135
|
SECONDARY outcome
Timeframe: Day 1-Day 15 in each of 5 treatment periodsPopulation: Modified Intent-to-Treat (mITT) population was a subset of the Intent-to-Treat (ITT) Population and included all subjects who received treatment, had post-treatment efficacy data from at least two treatment periods, and did not hav e a major protocol violation that would preclude the use of data from these periods.
FEV1 AUC0-3 is the area under the curve for the change from baseline in FEV1 calculated using the trapezoidal rule. All observed data will be used with the trapezoidal rule to calculate AUC. To aid in interpretation, all AUC values will be normalized by dividing the AUC by the time from the first to the last non-missing value (typically 3 hours).
Outcome measures
| Measure |
GP MDI 28.8 µg
n=101 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=212 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=204 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=109 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=99 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=158 Participants
Placebo MDI.
|
SAL 50 µg
n=155 Participants
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
FEV1 AUC0-3 on Day 15
|
0.191 Liter
Standard Error 0.0170
|
0.167 Liter
Standard Error 0.0131
|
0.146 Liter
Standard Error 0.0133
|
0.147 Liter
Standard Error 0.0165
|
0.113 Liter
Standard Error 0.0173
|
0.038 Liter
Standard Error 0.0144
|
0.190 Liter
Standard Error 0.0146
|
SECONDARY outcome
Timeframe: Day 1-Day 15 in each of 5 treatment periodsPopulation: Modified Intent-to-Treat (mITT) population was a subset of the Intent-to-Treat (ITT) Population and included all subjects who received treatment, had post-treatment efficacy data from at least two treatment periods, and did not hav e a major protocol violation that would preclude the use of data from these periods.
Change from baseline in average daily pre-dose peak expiratory flow rate (PEFR) over 14 days Daily pre-dose PEFR and daily post-dose PEFR will each be calculated as the average of the AM and PM measurements recorded for a given day. If either the AM or PM assessment is missing, only the single measurement will be used. Analyses of average daily pre-dose PEFR, average daily post-dose PEFR, and rescue Ventolin HFA usage will use the average of the non-missing daily values recorded in the subject diaries over each week and over the last week of treatment within each period.
Outcome measures
| Measure |
GP MDI 28.8 µg
n=105 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=209 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=205 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=108 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=97 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=158 Participants
Placebo MDI.
|
SAL 50 µg
n=152 Participants
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Average Daily Pre-dose PEFR Over 14 Days
|
5.01 L/min
Standard Error 4.947
|
-6.54 L/min
Standard Error 4.032
|
-10.65 L/min
Standard Error 4.052
|
-2.98 L/min
Standard Error 4.905
|
-10.52 L/min
Standard Error 5.130
|
-22.57 L/min
Standard Error 4.345
|
-3.00 L/min
Standard Error 4.417
|
SECONDARY outcome
Timeframe: Day 1-Day 15 in each of 5 treatment periodsPopulation: Modified Intent-to-Treat (mITT) population was a subset of the Intent-to-Treat (ITT) Population and included all subjects who received treatment, had post-treatment efficacy data from at least two treatment periods, and did not hav e a major protocol violation that would preclude the use of data from these periods.
Daily pre-dose PEFR and daily post-dose PEFR will each be calculated as the average of the AM and PM measurements recorded for a given day. If either the AM or PM assessment is missing, only the single measurement will be used. Analyses of average daily pre-dose PEFR, average daily post-dose PEFR, and rescue Ventolin HFA usage will use the average of the non-missing daily values recorded in the subject diaries over each week and over the last week of treatment within each period.
Outcome measures
| Measure |
GP MDI 28.8 µg
n=104 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=208 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=205 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=107 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=99 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=159 Participants
Placebo MDI.
|
SAL 50 µg
n=153 Participants
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Average Daily Post-dose PEFR Over 14 Days
|
5.53 L/min
Standard Error 4.568
|
-2.86 L/min
Standard Error 3.790
|
-5.38 L/min
Standard Error 3.801
|
3.09 L/min
Standard Error 4.530
|
-5.68 L/min
Standard Error 4.680
|
-21.65 L/min
Standard Error 4.041
|
3.55 L/min
Standard Error 4.103
|
SECONDARY outcome
Timeframe: Day 1-Day 15 in each of 5 treatment periodsPopulation: Modified Intent-to-Treat (mITT) population was a subset of the Intent-to-Treat (ITT) Population and included all subjects who received treatment, had post-treatment efficacy data from at least two treatment periods, and did not hav e a major protocol violation that would preclude the use of data from these periods.
Daily pre-dose PEFR and daily post-dose PEFR will each be calculated as the average of the AM and PM measurements recorded for a given day. If either the AM or PM assessment is missing, only the single measurement will be used. Analyses of average daily pre-dose PEFR, average daily post-dose PEFR, and rescue Ventolin HFA usage will use the average of the non-missing daily values recorded in the subject diaries over each week and over the last week of treatment within each period.
Outcome measures
| Measure |
GP MDI 28.8 µg
n=107 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=210 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=209 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=109 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=100 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=161 Participants
Placebo MDI.
|
SAL 50 µg
n=154 Participants
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Average Daily Rescue Medication Use Over 14 Days
|
-0.42 Puffs
Standard Error 0.132
|
-0.25 Puffs
Standard Error 0.105
|
-0.24 Puffs
Standard Error 0.105
|
-0.24 Puffs
Standard Error 0.131
|
-0.23 Puffs
Standard Error 0.136
|
-0.11 Puffs
Standard Error 0.114
|
-0.63 Puffs
Standard Error 0.116
|
SECONDARY outcome
Timeframe: Day 1-Day 15 in each of 5 treatment periodsPopulation: Modified Intent-to-Treat (mITT) population. The modified intent-to-treat (mITT) population included all randomized patients who received at least one dose of study drug. Patients were analyzed according to the treatment they received.
The ACQ-5 measures 5 symptoms (woken at night by symptoms, wake in the morning with symptoms, limitation of daily activities, shortness of breath, and wheeze). The scale is 0-6, where 0=minimum and 6=maximum
Outcome measures
| Measure |
GP MDI 28.8 µg
n=106 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=215 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=211 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=110 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=101 Participants
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=160 Participants
Placebo MDI.
|
SAL 50 µg
n=158 Participants
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Asthma Control Questionnaire (ACQ-5) on Day 15
|
-0.167 Scores on a scale
Standard Error 0.0586
|
-0.173 Scores on a scale
Standard Error 0.0453
|
-0.113 Scores on a scale
Standard Error 0.0455
|
-0.100 Scores on a scale
Standard Error 0.0578
|
-0.205 Scores on a scale
Standard Error 0.0602
|
-0.056 Scores on a scale
Standard Error 0.0501
|
-0.304 Scores on a scale
Standard Error 0.0505
|
Adverse Events
GP MDI 28.8 µg
GP MDI 14.4 µg
GP MDI 7.2 µg
GP MDI 3.6 µg
GP MDI 1.9 µg
Placebo MDI
SAL 50 µg
Serious adverse events
| Measure |
GP MDI 28.8 µg
n=112 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=230 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=228 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=118 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=107 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=174 participants at risk
Placebo MDI.
|
SAL 50 µg
n=167 participants at risk
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
Infections and infestations
Gastroenteritis, viral
|
0.00%
0/112 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
0.00%
0/230 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
0.00%
0/228 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
0.00%
0/118 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
0.00%
0/107 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
0.57%
1/174 • Number of events 1 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
0.00%
0/167 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
Other adverse events
| Measure |
GP MDI 28.8 µg
n=112 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 28.8 µg
|
GP MDI 14.4 µg
n=230 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 14.4 µg
|
GP MDI 7.2 µg
n=228 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 7.2 µg
|
GP MDI 3.6 µg
n=118 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 3.6 µg
|
GP MDI 1.9 µg
n=107 participants at risk
Glycopyrronium Metered Dose Inhaler (GP MDI) 1.9 µg
|
Placebo MDI
n=174 participants at risk
Placebo MDI.
|
SAL 50 µg
n=167 participants at risk
salmeterol 50 µg
|
|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Dry Mouth
|
8.0%
9/112 • Number of events 9 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
6.5%
15/230 • Number of events 15 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
7.0%
16/228 • Number of events 17 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
6.8%
8/118 • Number of events 8 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
7.5%
8/107 • Number of events 8 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
7.5%
13/174 • Number of events 13 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
5.4%
9/167 • Number of events 9 • Adverse events captured from Day 1 through Final Follow up Visit, which is 7-14 days post last study drug dose, unless serious. If serious, they are captured from screening Visit 1 through Final Follow up Visit
Safety Population includes all subjects who were randomized to treatment and received at least one dose of study treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent it's opinions, or the opinions of the publication committee, if these differ with the proposed publication.
- Publication restrictions are in place
Restriction type: OTHER