Glycopyrrolate/Formoterol Fumarate MDI Compared With Spiriva® as An Active Control in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

• Sponsor: Pearl Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01587079
• Collaborator: (none)
• Enrollment: 159
• Locations: 19
• Arms: 8
• Duration (Months): 6
• Patients Per Site: 8.4
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the efficacy of Glycopyrrolate/Formoterol Fumarate MDI relative to individual components (GP MDI and FF MDI) in subjects with moderate to severe COPD

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: PT003; Drug: PT001; Drug: PT005; Drug: Tiotropium inhalation powder	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 159 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, (Test Products), Chronic Dosing (7 Days), Four Period, Eight Treatment , Incomplete Block, Cross Over, Multi Center Study to Assess Efficacy and Safety of Five Doses of PT003, One Dose of PT001 and One Dose of PT005 in Patients With Moderate to Severe COPD, Compared With Spiriva® Handihaler® (Tiotropium Bromide 18 µg, Open Label) as Active Control
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PT003 (Dose 1) PT003 MDI Dose 1	Drug: PT003; PT003 MDI administered as two puffs BID for 7 days
Experimental: PT003 (Dose 2) PT003 MDI Dose 2	Drug: PT003; PT003 MDI administered as two puffs BID for 7 days
Experimental: PT003 (Dose 3) PT003 MDI Dose 3	Drug: PT003; PT003 MDI administered as two puffs BID for 7 days
Experimental: PT003 (Dose 4) PT003 MDI Dose 4	Drug: PT003; PT003 MDI administered as two puffs BID for 7 days
Experimental: PT003 (Dose 5) PT003 MDI Dose 5	Drug: PT003; PT003 MDI administered as two puffs BID for 7 days
Experimental: PT001 PT001 MDI	Drug: PT001; PT001 MDI administered as two puffs BID for 7 days
Experimental: PT005 PT005 MDI	Drug: PT005; PT005 MDI administered as two puffs BID for 7 days
Active Comparator: Spiriva® Handihaler® Tiotropium Bromide	Drug: Tiotropium inhalation powder; Taken as 1 capsule containing 18 µg of Tiotropium via the Handihaler DPI for 7 days

Outcome Measures

Primary Outcome Measures

1. FEV1 AUC 0-12 on Day 7 [Day 7]

   FEV1 AUC 0-12

Secondary Outcome Measures

1. Peak Change From Baseline in FEV1 on Treatment Day 1 [Day 1]

   Peak change from Baseline in FEV1 on Treatment

2. Time to Onset of Action (>10% Improvement in FEV1) on Day 1 [Day 1]

   Time to onset of action (>10% improvement in FEV1)

3. Proportion of Subjects Achieving >=12% Improvement in FEV1 on Day 1 [Day 1]

   Proportion of subjects achieving >=12% improvement in FEV1

4. Peak Change From Baseline in Inspiratory Capacity on Day 1 [Day 1]

   Peak change from baseline in Inspiratory Capacity

5. Change From Baseline in Morning Pre-dose Trough FEV1 on Day 7 [Day 7]

   Change from baseline in morning pre-dose trough FEV1

6. Peak Change From Baseline in FEV1 on Day 7 [Day 7]

   Peak change from baseline in FEV1 Day 7

7. Change From Baseline in Morning Pre-dose Trough IC on Day 7 [Day 7]

   Change from baseline in morning pre-dose trough IC

8. Peak Change From Baseline IC on Day 7 [Day 7]

   Peak change from baseline IC

9. Change From Baseline at Evening 12-hour Post-dose Trough FEV1 on Day 7 [Day 7]

   Change from baseline at evening 12-hour post-dose trough FEV1

10. Change From Baseline in Mean Morning Pre-dose Daily Peak Flow Readings on Day 7 [Day 7]

    Change from baseline in mean morning pre-dose daily peak flow readings

11. Change From Baseline in Mean Morning Post-dose Daily Peak Flow Readings on Day 7 [Day 7]

    Change from baseline in mean morning post-dose daily peak flow readings on

12. Change From Baseline in Mean Evening Pre-dose Daily Peak Flow Readings on Day 7 [Day 7]

    Change from baseline in mean evening pre-dose daily peak flow readings (BID treatments only)

13. Change From Baseline in Mean Evening Post-dose Daily Peak Flow Readings on Day 7 [Day 7]

    Change from baseline in mean evening post-dose daily peak flow readings (12 Hours post-dose for Spiriva)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Signed written informed consent

• 40 - 80 years of age

• Clinical history of COPD with airflow limitation that is not fully reversible

• Females of non-child bearing potential or females of child bearing potential with negative pregnancy test and acceptable contraceptive methods

• Current/former smokers with at least a 10 pack-year history of cigarette smoking

• A measured post-bronchodilator FEV1/FVC ratio of < or = 0.70

• A measured post-bronchodilator FEV1 > or = 750ml or 30% predicted and < or = 80% of predicted normal values

• Able to change COPD treatment as required by protocol

Key Exclusion Criteria:

• Women who are pregnant or lactating

• Primary diagnosis of asthma

• Alpha-1 antitrypsin deficiency as the cause of COPD

• Active pulmonary diseases

• Prior lung volume reduction surgery

• Abnormal chest X-ray not due to the presence of COPD

• Hospitalized due to poorly controlled COPD within 3 months of Screening

• Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG, uncontrolled hypertension, glaucoma, symptomatic prostatic hypertrophy)

• Cancer that has not been in complete remission for at least 5 years

• Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives

Other inclusion/exclusion criteria as defined in the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pearl Investigative Site	Glendale	Arizona	United States
2	Pearl Investigative Site	Rancho Mirage	California	United States
3	Pearl Investigative Site	Waterbury	Connecticut	United States
4	Pearl Investigative Site	Clearwater	Florida	United States	33765
5	Pearl Investigative Site	Clearwater	Florida	United States
6	Pearl Investigative Site	Pensacola	Florida	United States
7	Pearl Investigative Site	Winter Park	Florida	United States	32789
8	Pearl Investigative Site	Lafayette	Louisiana	United States
9	Pearl Investigative Site	North Dartmouth	Massachusetts	United States
10	Pearl Investigative Site	Fridley	Minnesota	United States
11	Pearl Investigative Site	St. Louis	Missouri	United States
12	Pearl Investigative Site	Summit	New Jersey	United States
13	Pearl Investigative Site	Cincinnati	Ohio	United States
14	Pearl Investigative Site	Medford	Oregon	United States	97504
15	Pearl Investigative Site	Medford	Oregon	United States
16	Pearl Investigative Site	Rock Hill	South Carolina	United States
17	Pearl Investigative Site	Spartanburg	South Carolina	United States	29303
18	Pearl Investigative Site	San Antonio	Texas	United States
19	Pearl Investigative Site	Morgantown	West Virginia	United States

Sponsors and Collaborators

• Pearl Therapeutics, Inc.

Investigators

• Study Director: Colin Reisner, MD, Pearl Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pearl Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01587079
• Other Study ID Numbers: PT003005
• First Posted: Apr 27, 2012
• Last Update Posted: Jun 30, 2016
• Last Verified: May 1, 2016

• Keywords provided by Pearl Therapeutics, Inc.: COPD
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

Study Results

Participant Flow

Recruitment Details	The study was conducted at 20 sites in the US from May 2012 until September 2012. The entire study was scheduled to take a maximum of 19 weeks for each individual subject.
Pre-assignment Detail	Study was a chronic dosing (7 days), 4-period, 8-treatment, Incomplete Block, Cross-Over.

Arm/Group Title	All Subjects
Arm/Group Description
Period Title: Overall Study
STARTED	159
COMPLETED	120
NOT COMPLETED	39

Baseline Characteristics

Arm/Group Title	All Subjects Screened
Arm/Group Description
Overall Participants	159
Age (years) [Mean (Standard Deviation) ]
Age, years	62.8 (8.6)
Sex: Female, Male (Count of Participants)
Female	76 (47.8) 47.8%
Male	83 (52.2) 52.2%

Outcome Measures

1. Primary Outcome

Title	FEV1 AUC 0-12 on Day 7
Description	FEV1 AUC 0-12
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI 18 μg (PT001)	GFF MDI 18/9.6 μg (PT003)	GFF/MDI 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI 2.4/9.6 μg (PT003)	GFF MDI 1.2/9.6 μg (PT003)	FF MDI 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	18 μg	18/9.6 μg	9/9.6 μg	4.6/9.6 μg	2.4/9.6 μg	1.2/9.6 μg	9.6 μg	18 μg QD
Measure Participants	57	59	52	57	57	60	57	60
Least Squares Mean (95% Confidence Interval) [Liters]	1.452	1.591	1.547	1.539	1.538	1.508	1.467	1.489

2. Secondary Outcome

Title	Peak Change From Baseline in FEV1 on Treatment Day 1
Description	Peak change from Baseline in FEV1 on Treatment
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg QD
Measure Participants	59	63	56	60	60	64	59	63
Least Squares Mean (95% Confidence Interval) [Milliliters]	209	339	329	348	333	312	317	238

3. Secondary Outcome

Title	Time to Onset of Action (>10% Improvement in FEV1) on Day 1
Description	Time to onset of action (>10% improvement in FEV1)
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg QD
Measure Participants	60	62	55	58	60	64	60	62
15 minutes	27	65	51	62	65	66	60	37
30 minutes	8	18	13	10	10	9	3	21
1 hour	15	6	11	12	12	5	12	11
2 hours	10	5	7	5	2	9	3	5
No onset within 2 hours	40	6	18	10	12	11	22	26

4. Secondary Outcome

Title	Proportion of Subjects Achieving >=12% Improvement in FEV1 on Day 1
Description	Proportion of subjects achieving >=12% improvement in FEV1
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	GP MDI 18 μg (PT001)
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg
Measure Participants	60	63	55	59	61	65	61	63
Number [Percentage]	56	93	85	84	86	83	80	72

5. Secondary Outcome

Title	Peak Change From Baseline in Inspiratory Capacity on Day 1
Description	Peak change from baseline in Inspiratory Capacity
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg QD
Measure Participants	60	63	56	61	61	65	62	63
Least Squares Mean (95% Confidence Interval) [Milliliters]	204	393	320	387	347	348	335	233

6. Secondary Outcome

Title	Change From Baseline in Morning Pre-dose Trough FEV1 on Day 7
Description	Change from baseline in morning pre-dose trough FEV1
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg QD
Measure Participants	60	62	56	61	60	65	60	63
Least Squares Mean (95% Confidence Interval) [Milliliters]	120	183	150	154	163	130	104	122

7. Secondary Outcome

Title	Peak Change From Baseline in FEV1 on Day 7
Description	Peak change from baseline in FEV1 Day 7
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg QD
Measure Participants	60	63	55	60	61	64	60	63
Least Squares Mean (95% Confidence Interval) [Millliters]	300	444	414	403	388	363	332	309

8. Secondary Outcome

Title	Change From Baseline in Morning Pre-dose Trough IC on Day 7
Description	Change from baseline in morning pre-dose trough IC
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg QD
Measure Participants	60	63	56	61	61	63	62	63
Least Squares Mean (95% Confidence Interval) [Millliters]	109	185	183	215	203	151	129	106

9. Secondary Outcome

Title	Peak Change From Baseline IC on Day 7
Description	Peak change from baseline IC
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg QD
Measure Participants	60	63	56	61	61	65	62	63
Least Squares Mean (95% Confidence Interval) [Millliters]	223	430	441	409	368	371	377	241

10. Secondary Outcome

Title	Change From Baseline at Evening 12-hour Post-dose Trough FEV1 on Day 7
Description	Change from baseline at evening 12-hour post-dose trough FEV1
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI BID 18 μg	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI BID 1.2/9.6 μg	FF MDI BID 9.6 μg	Spiriva 18 μg QD
Arm/Group Description	BID 18 μg	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	BID 1.2/9.6 μg	BID 9.6 μg	18 μg QD
Measure Participants	57	61	53	59	57	61	59	61
Least Squares Mean (95% Confidence Interval) [Millliters]	99	196	162	118	133	110	73	130

11. Secondary Outcome

Title	Change From Baseline in Mean Morning Pre-dose Daily Peak Flow Readings on Day 7
Description	Change from baseline in mean morning pre-dose daily peak flow readings
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI 18 μg BID	GFF MDI 18/9.6 μg BID	GFF/MDI 9/9.6 μg BID	GFF MDI BID 4.6/9.6 μg	GFF MDI 2.4/9.6 μg BID	GFF MDI 1.2/9.6 μg BID	FF MDI 9.6 μg BID	Spiriva 18 μg QD
Arm/Group Description	18 μg BID	18/9.6 μg BID	9/9.6 μg BID	4.6/9.6 μg	2.4/9.6 μg BID	1.2/9.6 μg BID	9.6 μg BID	18 μg QD
Measure Participants	59	63	56	61	61	64	62	62
Least Squares Mean (95% Confidence Interval) [L/min]	7.6	25.2	16.6	12.4	18.0	13.8	8.6	11.6

12. Secondary Outcome

Title	Change From Baseline in Mean Morning Post-dose Daily Peak Flow Readings on Day 7
Description	Change from baseline in mean morning post-dose daily peak flow readings on
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI 18 μg BID	GFF MDI BID 18/9.6 μg	GFF/MDI BID 9/9.6 μg	GFF MDI BID 4.6/9.6 μg	GFF MDI BID 2.4/9.6 μg	GFF MDI 1.2/9.6 μg BID	FF MDI 9.6 μg BID	Spiriva 18 μg QD
Arm/Group Description	18 μg BID	BID 18/9.6 μg	BID 9/9.6 μg	4.6/9.6 μg	BID 2.4/9.6 μg	1.2/9.6 μg BID	9.6 μg BID	18 μg QD
Measure Participants	59	62	56	61	61	64	62	62
Least Squares Mean (95% Confidence Interval) [L/min]	31.0	58.8	55.0	46.7	52.1	49.6	43.2	37.9

13. Secondary Outcome

Title	Change From Baseline in Mean Evening Pre-dose Daily Peak Flow Readings on Day 7
Description	Change from baseline in mean evening pre-dose daily peak flow readings (BID treatments only)
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI 18 μg BID	GFF MDI 18/9.6 μg BID	GFF/MDI 9/9.6 μg BID	GFF MDI 4.6/9.6 μg BID	GFF MDI 2.4/9.6 μg BID	GFF MDI 1.2/9.6 μg BID	FF MDI 9.6 μg BID	Spiriva18 μg QD
Arm/Group Description	18 μg BID	18/9.6 μg BID	9/9.6 μg BID	4.6/9.6 μg BID	2.4/9.6 μg BID	1.2/9.6 μg BID	9.6 μg BID	18 μg QD
Measure Participants	57	59	56	58	60	63	62	0
Least Squares Mean (95% Confidence Interval) [L/min]	11.7	32.5	25.0	19.0	25.6	19.9	16.5

14. Secondary Outcome

Title	Change From Baseline in Mean Evening Post-dose Daily Peak Flow Readings on Day 7
Description	Change from baseline in mean evening post-dose daily peak flow readings (12 Hours post-dose for Spiriva)
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	GP MDI 18 μg BID	GFF MDI 18/9.6 μg BID	GFF/MDI 9/9.6 μg BID	GFF MDI BID 4.6/9.6 μg BID	GFF MDI 2.4/9.6 μg BID	GFF MDI 1.2/9.6 μg BID	FF MDI 9.6 μg BID	Spiriva 18 μg QD
Arm/Group Description	18 μg BID	18/9.6 μg BID	9/9.6 μg BID	4.6/9.6 μg BID	2.4/9.6 μg BID	1.2/9.6 μg BID	9.6 μg BID	18 μg QD
Measure Participants	57	57	56	58	60	63	62	60
Least Squares Mean (95% Confidence Interval) [L/min]	35.0	61.5	56.1	51.5	53.7	53.8	48.3	30.3

Adverse Events

Time Frame	SAEs and AEs were collected throughout study participation and up to 14 days following the last dose of study drug.
Adverse Event Reporting Description	Safety Population - All subjects who were randomized, received at least 1 dose of a study treatment, and had a post-baseline safety assessment for that treatment.
Arm/Group Title	GP MDI 18 μg (PT001)		GFF MDI 18/9.6 μg (PT003)		GFF MDI 9/9.6 μg (PT003)		GFF MDI 4.6/9.6 μg (PT003)		GFF MDI 2.4/9.6 μg (PT003)		GFF MDI 1.2/9.6 μg (PT003)		FF MDI 9.6 μg (PT005)		Spiriva
Arm/Group Description	18 μg		18/9.6 μg		9/9.6 μg		4.6/9.6 μg		2.4/9.6 μg		1.2/9.6 μg		9.6 μg		18 μg
All Cause Mortality
	GP MDI 18 μg (PT001)		GFF MDI 18/9.6 μg (PT003)		GFF MDI 9/9.6 μg (PT003)		GFF MDI 4.6/9.6 μg (PT003)		GFF MDI 2.4/9.6 μg (PT003)		GFF MDI 1.2/9.6 μg (PT003)		FF MDI 9.6 μg (PT005)		Spiriva
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	GP MDI 18 μg (PT001)		GFF MDI 18/9.6 μg (PT003)		GFF MDI 9/9.6 μg (PT003)		GFF MDI 4.6/9.6 μg (PT003)		GFF MDI 2.4/9.6 μg (PT003)		GFF MDI 1.2/9.6 μg (PT003)		FF MDI 9.6 μg (PT005)		Spiriva
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/66 (1.5%)		1/71 (1.4%)		0/70 (0%)		0/67 (0%)		1/71 (1.4%)		2/68 (2.9%)		1/73 (1.4%)		0/71 (0%)
Cardiac disorders
Cardio-Respiratory arrest	0/66 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/67 (0%)	0	0/71 (0%)	0	1/68 (1.5%)	1	0/73 (0%)	0	0/71 (0%)	0
Tachycardia	0/66 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/67 (0%)	0	0/71 (0%)	0	1/68 (1.5%)	1	0/73 (0%)	0	0/71 (0%)	0
General disorders
Sudden Death	0/66 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/67 (0%)	0	0/71 (0%)	0	0/68 (0%)	0	1/73 (1.4%)	1	0/71 (0%)	0
Injury, poisoning and procedural complications
Spinal Compression fracture	0/66 (0%)	0	0/71 (0%)	0	0/70 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1	0/68 (0%)	0	0/73 (0%)	0	0/71 (0%)	0
Nervous system disorders
Transient Ischaemic attack	0/66 (0%)	0	1/71 (1.4%)	1	0/70 (0%)	0	0/67 (0%)	0	0/71 (0%)	0	0/68 (0%)	0	0/73 (0%)	0	0/71 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/66 (1.5%)	1	0/71 (0%)	0	0/70 (0%)	0	0/67 (0%)	0	0/71 (0%)	0	0/68 (0%)	0	0/73 (0%)	0	0/71 (0%)	0
Other (Not Including Serious) Adverse Events
	GP MDI 18 μg (PT001)		GFF MDI 18/9.6 μg (PT003)		GFF MDI 9/9.6 μg (PT003)		GFF MDI 4.6/9.6 μg (PT003)		GFF MDI 2.4/9.6 μg (PT003)		GFF MDI 1.2/9.6 μg (PT003)		FF MDI 9.6 μg (PT005)		Spiriva
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/66 (12.1%)		2/71 (2.8%)		8/70 (11.4%)		5/67 (7.5%)		9/71 (12.7%)		2/68 (2.9%)		8/73 (11%)		6/71 (8.5%)
Gastrointestinal disorders
Dry Mouth	8/66 (12.1%)	8	2/71 (2.8%)	2	3/70 (4.3%)	3	3/67 (4.5%)	3	5/71 (7%)	5	1/68 (1.5%)	1	6/73 (8.2%)	8	6/71 (8.5%)	6
Nervous system disorders
Tremor	0/66 (0%)	0	0/71 (0%)	0	5/70 (7.1%)	5	2/67 (3%)	2	4/71 (5.6%)	4	1/68 (1.5%)	1	2/73 (2.7%)	2	0/71 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 its opinions, or the opinions of the publication committee, if these differ with the proposed publication.