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A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® (Kronos) (KRONOS)

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ClinicalTrials.gov Identifier: NCT02497001
Recruitment Status : Completed
First Posted : July 14, 2015
Results First Posted : December 24, 2020
Last Update Posted : December 24, 2020
Sponsor:
Information provided by (Responsible Party):
Pearl Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition COPD
Interventions Drug: BGF MDI 320/14.4/9.6 μg
Drug: GFF MDI (PT003) 14.4/9.6 μg
Drug: BFF MDI (PT009) 320/9.6 μg
Drug: Symbicort® Turbuhaler® (TBH) Inhalation Powder
Enrollment 1902
Recruitment Details This study was conducted at 208 sites in four countries, from August 2015 until January 2018. The entire study period could take up to a maximum of 30 weeks.
Pre-assignment Details Subjects were randomized in a 2:2:1:1 scheme.
Arm/Group Title BGF MDI 320/14.4/9.6 ug GFF MDI 14.4/9.6 ug BFF MDI 320/9.6 ug Symbicort TBH 400/12 ug
Hide Arm/Group Description Budesonide Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 320/14.4/9.6 ug Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 14.4/9.6 ug Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 ug Symbicort Turbuhaler 400/12 ug
Period Title: Overall Study
Started 640 627 316 319
Completed 566 524 266 278
Not Completed 74 103 50 41
Reason Not Completed
Lost to Follow-up             10             2             0             2
Adverse Event             28             30             11             11
Withdrawal by Subject             14             37             19             15
Physician Decision             5             11             5             1
subjects that were not treated             1             2             2             1
Major Protocol Deviation             3             4             4             4
Lack of Efficacy             10             16             6             6
Protocol Violation             3             1             3             1
Arm/Group Title BGF MDI 320/14.4/9.6 ug GFF MDI 14.4/9.6 ug BFF MDI 320/9.6 ug Symbicort TBH 400/12 ug Total
Hide Arm/Group Description Budesonide Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 320/14.4/9.6 ug Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 14.4/9.6 ug Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 ug Symbicort Turbuhaler 400/12 ug Total of all reporting groups
Overall Number of Baseline Participants 639 625 314 318 1896
Hide Baseline Analysis Population Description
mITT - Modified Intent to Treat
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 639 participants 625 participants 314 participants 318 participants 1896 participants
64.9  (7.8) 65.1  (7.7) 65.2  (7.2) 65.9  (7.7) 65.2  (7.7)
[1]
Measure Analysis Population Description: mITT
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 639 participants 625 participants 314 participants 318 participants 1896 participants
Female
179
  28.0%
195
  31.2%
90
  28.7%
82
  25.8%
546
  28.8%
Male
460
  72.0%
430
  68.8%
224
  71.3%
236
  74.2%
1350
  71.2%
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 639 participants 625 participants 314 participants 318 participants 1896 participants
Hispanic or Latino
16
   2.5%
14
   2.2%
7
   2.2%
4
   1.3%
41
   2.2%
Not Hispanic or Latino
623
  97.5%
611
  97.8%
305
  97.1%
312
  98.1%
1851
  97.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
2
   0.6%
2
   0.6%
4
   0.2%
[1]
Measure Analysis Population Description: mITT
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 639 participants 625 participants 314 participants 318 participants 1896 participants
American Indian or Alaska Native
1
   0.2%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.1%
Asian
284
  44.4%
285
  45.6%
142
  45.2%
141
  44.3%
852
  44.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.1%
Black or African American
23
   3.6%
38
   6.1%
15
   4.8%
14
   4.4%
90
   4.7%
White
329
  51.5%
301
  48.2%
157
  50.0%
163
  51.3%
950
  50.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   0.3%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.1%
[1]
Measure Analysis Population Description: mITT
1.Primary Outcome
Title FEV1 AUC0-4
Hide Description FEV1 AUC0-4 (L) for The Efficacy Estimand (Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4) AUC was normalized for length of follow up (e.g. typically 4 hours)).
Time Frame at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population total numbers may vary based on predefined subject exclusions prior to study unblinding
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 436 403 201 211
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.292
(0.271 to 0.314)
0.288
(0.266 to 0.310)
0.177
(0.146 to 0.207)
0.189
(0.160 to 0.219)
2.Primary Outcome
Title Change From Baseline in Morning Pre-dose Trough FEV1
Hide Description Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand
Time Frame at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 565 522 266 276
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.124
(0.108 to 0.140)
0.111
(0.094 to 0.127)
0.050
(0.027 to 0.072)
0.062
(0.039 to 0.084)
3.Secondary Outcome
Title Change From Baseline in Morning Pre-dose Trough FEV1
Hide Description Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand
Time Frame over 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 622 601 300 301
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.147
(0.134 to 0.159)
0.125
(0.112 to 0.137)
0.073
(0.055 to 0.091)
0.088
(0.070 to 0.105)
4.Secondary Outcome
Title Peak Change From Baseline in FEV1 Within 4 Hours Post-dosing
Hide Description Peak Change from Baseline in FEV1 (L) Within 4 Hours Post-Dose for The Efficacy Estimand
Time Frame at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 436 403 201 211
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.370
(0.348 to 0.393)
0.361
(0.338 to 0.384)
0.253
(0.221 to 0.284)
0.264
(0.233 to 0.295)
5.Secondary Outcome
Title Rate of Moderate or Severe COPD Exacerbations
Hide Description Rate of Moderate or Severe COPD Exacerbations for the Efficacy Estimand
Time Frame over 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 108 157 65 61
Least Squares Mean (Standard Error)
Unit of Measure: Exacerbations
0.46  (0.05) 0.95  (0.09) 0.56  (0.08) 0.55  (0.08)
6.Secondary Outcome
Title Percentage of Subjects Achieving a Minimal Clinically Important Difference (MCID) of 4 Units or More in SGRQ Total Score (SGRQ Responders)
Hide Description Change from BGF
Time Frame at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 625 314 318
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percentage
6.06
(0.30 to 11.82)
6.43
(-0.62 to 13.47)
8.23
(1.23 to 15.22)
7.Secondary Outcome
Title Change From Baseline in Average Daily Rescue Ventolin HFA Use
Hide Description Change from Baseline in Mean Daily Number of Puffs of Rescue Ventolin HFA for The Efficacy Estimand
Time Frame over 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 141 155 269 233
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Puffs
-1.3
(-1.6 to -1.1)
-1.1
(-1.3 to -0.8)
-1.1
(-1.5 to -0.8)
-1.6
(-1.9 to -1.2)
8.Secondary Outcome
Title Time to Onset of Action on Day 1, 5 Minutes Post Dose
Hide Description FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 429 417 220 210
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.181
(0.169 to 0.192)
0.194
(0.182 to 0.205)
0.167
(0.152 to 0.182)
0.163
(0.148 to 0.178)
9.Secondary Outcome
Title Time to Onset of Action on Day 1, 15 Minutes Post Dose
Hide Description FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 484 470 238 238
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.217
(0.205 to 0.230)
0.230
(0.218 to 0.243)
0.197
(0.180 to 0.213)
0.190
(0.174 to 0.207)
10.Secondary Outcome
Title Time to Onset of Action on Day 1, 30 Minutes Post Dose
Hide Description FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 490 474 242 238
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.236
(0.223 to 0.249)
0.255
(0.242 to 0.268)
0.213
(0.195 to 0.230)
0.208
(0.190 to 0.225)
11.Secondary Outcome
Title Time to Onset of Action on Day 1, 1 Hour Post Dose
Hide Description FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 497 481 244 245
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.268
(0.254 to 0.282)
0.282
(0.268 to 0.296)
0.228
(0.208 to 0.247)
0.232
(0.213 to 0.251)
12.Secondary Outcome
Title Time to Onset of Action on Day 1, 2 Hours Post Dose
Hide Description FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 494 480 243 246
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.281
(0.266 to 0.295)
0.292
(0.277 to 0.307)
0.241
(0.220 to 0.261)
0.244
(0.224 to 0.265)
13.Secondary Outcome
Title Time to Onset of Action on Day 1, 4 Hours Post Dose
Hide Description FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title BGF MDI 320/14.4/9.6 μg GFF MDI (PT003) 14.4/9.6 μg BFF MDI (PT009) 320/9.6 μg Symbicort®
Hide Arm/Group Description:
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Symbicort® Turbuhaler® (TBH) Inhalation Powder
Overall Number of Participants Analyzed 491 477 243 244
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.276
(0.260 to 0.292)
0.278
(0.262 to 0.294)
0.234
(0.213 to 0.256)
0.247
(0.225 to 0.268)
Time Frame Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized.
Adverse Event Reporting Description The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
 
Arm/Group Title BGF MDI 320/14.4/9.6 ug GFF MDI 14.4/9.6 ug BFF MDI 320/9.6 ug Symbicort TBH 400/12 ug
Hide Arm/Group Description Budesonide Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 320/14.4/9.6 ug Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 14.4/9.6 ug Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 ug Symbicort Turbuhaler 400/12 ug
All-Cause Mortality
BGF MDI 320/14.4/9.6 ug GFF MDI 14.4/9.6 ug BFF MDI 320/9.6 ug Symbicort TBH 400/12 ug
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/639 (0.94%)      3/625 (0.48%)      2/314 (0.64%)      1/318 (0.31%)    
Hide Serious Adverse Events
BGF MDI 320/14.4/9.6 ug GFF MDI 14.4/9.6 ug BFF MDI 320/9.6 ug Symbicort TBH 400/12 ug
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   55/639 (8.61%)      68/625 (10.88%)      21/314 (6.69%)      29/318 (9.12%)    
Blood and lymphatic system disorders         
Anaemia  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Cardiac disorders         
Acute myocardial infarction  1  1/639 (0.16%)  1 2/625 (0.32%)  2 1/314 (0.32%)  1 1/318 (0.31%)  1
Coronary artery disease  1  1/639 (0.16%)  1 1/625 (0.16%)  1 1/314 (0.32%)  1 1/318 (0.31%)  1
Acute coronary syndrome  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 1/318 (0.31%)  1
Atrial fibrilation  1  2/639 (0.31%)  2 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Angina unstable  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Atrioventricular block complete  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Cardiac failure chronic  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Cardiac failure congestive  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Cardiac failure tamponade  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Cardio-respiratory arrest  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Coronary artery occlusion  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Myocardial ischaemia  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Eye disorders         
Cataract  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Gastrointestinal disorders         
Inguinal hernia  1  0/639 (0.00%)  0 2/625 (0.32%)  2 0/314 (0.00%)  0 0/318 (0.00%)  0
Anal fistula  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Colitis ulcerative  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Dysphagia  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
gastrointestinal haemorrhage  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Intestinal obstruction  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Intestinal polyp  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Large intestinal polyp  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Pancreatitis acute  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
General disorders         
Non-cardiac chest pain  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Death  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Systemic inflammatory response syndrome  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Hepatobiliary disorders         
Cholangitis  1  0/639 (0.00%)  0 1/625 (0.16%)  2 0/314 (0.00%)  0 0/318 (0.00%)  0
Bile duct stone  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Hepatic cyst  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Infections and infestations         
Pneumonia  1  8/639 (1.25%)  8 6/625 (0.96%)  6 1/314 (0.32%)  1 0/318 (0.00%)  0
Sepsis  1  1/639 (0.16%)  1 1/625 (0.16%)  1 1/314 (0.32%)  1 1/318 (0.31%)  1
Influenza  1  0/639 (0.00%)  0 1/625 (0.16%)  1 1/314 (0.32%)  1 0/318 (0.00%)  0
Appendicitis  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Cellulitis  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Clostridium difficile infection  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Dengue ferver  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Device related infection  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Diverticulitits  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Gastritis viral  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Gastroenteritis  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Herpes zoster  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Lung infection  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Lymphangitis  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Meningitis viral  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Osteomyelitis  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Pneumonia bacterial  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Pulmonary tuberculosis  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Pyelonephritis  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Upper respiratory tract infection  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Pyelonephritis acute  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Urinary tract infection  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Injury, poisoning and procedural complications         
Hip fracture  1  1/639 (0.16%)  1 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Pulmonary contusion  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Respiratory fume inhalation disorder  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Rib fracture  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Road traffic accident6  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Wrist fracture  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Investigations         
Electrocardiogram T wave inversion  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Metabolism and nutrition disorders         
Dehydration  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Intervertebral disc disorder  1  2/639 (0.31%)  2 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Intervertebral disc protrusion  1  1/639 (0.16%)  2 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Rheumatoid arthritis  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Rotator cuff syndrome  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adenocarcinoma  1  1/639 (0.16%)  1 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Colon cancer  1  1/639 (0.16%)  1 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Prostate cancer  2  1/639 (0.16%)  1 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Squamous cell carcinoma of lung  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 1/318 (0.31%)  1
Acute myeloid leukemia  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Brain cancer metastatic  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Colorectal cancer metastatic  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Gastric cancer  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Malignant neoplasm of thymus  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Lymphoma  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Metasteses of liver  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Metasteses to lung  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Metastases to spine  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Papilloma  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Rectal cancer  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Small cell lung cancer metastatic  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Urethral cancer  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Nervous system disorders         
Carotid artery stenosis  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Syncope  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Central nervous system lesion  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Cerebral infarction  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Cerebral ischeamia  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Cerebrovascular insufficiency  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Migraine  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Siezure  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Myelopathy  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Psychiatric disorders         
Delerium  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Major depression  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Suicide attempt  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Renal and urinary disorders         
Acute kidney injury  1  0/639 (0.00%)  0 1/625 (0.16%)  1 1/314 (0.32%)  1 0/318 (0.00%)  0
Ureterolithiasis  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Reproductive system and breast disorders         
Prostatitis  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease  1  17/639 (2.66%)  17 32/625 (5.12%)  41 8/314 (2.55%)  8 13/318 (4.09%)  16
Acute respiratory failure  1  4/639 (0.63%)  4 1/625 (0.16%)  1 0/314 (0.00%)  0 1/318 (0.31%)  1
Pneumothorax  1  2/639 (0.31%)  2 1/625 (0.16%)  2 1/314 (0.32%)  1 1/318 (0.31%)  1
Respiratory failure  1  1/639 (0.16%)  1 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Hypoxia  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Interstitial lung disease  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Lung infiltration  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Pneumonia aspiration  1  0/639 (0.00%)  0 0/625 (0.00%)  0 0/314 (0.00%)  0 1/318 (0.31%)  1
Pulmonary mass  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
Vascular disorders         
Arterial stenosis  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Hypertension  1  0/639 (0.00%)  0 1/625 (0.16%)  1 0/314 (0.00%)  0 0/318 (0.00%)  0
Iliac artery occlusion  1  1/639 (0.16%)  1 0/625 (0.00%)  0 0/314 (0.00%)  0 0/318 (0.00%)  0
Peripheral vascular disorder  1  0/639 (0.00%)  0 0/625 (0.00%)  0 1/314 (0.32%)  1 0/318 (0.00%)  0
1
Term from vocabulary, MedDRA
2
Term from vocabulary, nedDRA
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BGF MDI 320/14.4/9.6 ug GFF MDI 14.4/9.6 ug BFF MDI 320/9.6 ug Symbicort TBH 400/12 ug
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   126/639 (19.72%)      84/625 (13.44%)      59/314 (18.79%)      55/318 (17.30%)    
Infections and infestations         
Nasopharyngitits  1  49/639 (7.67%)  61 41/625 (6.56%)  48 26/314 (8.28%)  30 30/318 (9.43%)  32
Upper Respiratory Infection  1  65/639 (10.17%)  77 37/625 (5.92%)  41 18/314 (5.73%)  18 22/318 (6.92%)  23
Musculoskeletal and connective tissue disorders         
Muscle Spasms  1  21/639 (3.29%)  21 8/625 (1.28%)  9 17/314 (5.41%)  18 6/318 (1.89%)  6
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pearl Therapeutics Inc.
Organization: Pearl Therapeutics Inc.
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pearl Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02497001    
Other Study ID Numbers: PT010006
First Submitted: July 8, 2015
First Posted: July 14, 2015
Results First Submitted: March 26, 2020
Results First Posted: December 24, 2020
Last Update Posted: December 24, 2020