PT003 MDI Dose Confirmation Study

• Sponsor: Pearl Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01349816
• Collaborator: (none)
• Enrollment: 185
• Locations: 13
• Arms: 6
• Duration (Months): 5
• Patients Per Site: 14.2
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

The primary objective of this study is to demonstrate efficacy of PT003 MDI relative to its individual components (PT001 MDI and PT005 MDI) in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 185 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Chronic Dosing (7 Days), Two Period, Six Treatment, Incomplete Block, Cross Over, Multi Center Study to Assess Efficacy and Safety of Four Doses of PT003 MDI in Patients With Moderate to Severe COPD, Compared With Its Individual Components (PT005 MDI and PT001 MDI) as Active Controls
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

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: 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

Outcome Measures

Primary Outcome Measures

1. FEV1 AUC0-12 [Day 7]

   Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 relative to baseline following chronic dosing (1 week).

Secondary Outcome Measures

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

   Peak change from baseline in FEV1 through 2 hours

2. Time to Onset of Action [Day 1]

   At least 10% improvement in mean FEV1

3. At Least 12% Improvement in FEV1 [Day 1]

   Proportion of subjects achieving >=12% improvement in FEV1 relative to baseline

4. Peak Change in IC [Day 1]

   Mean inspiratory capacity (IC) of 1 and 2 hours post-dose minus baseline

5. Morning Pre-dose FEV1 [Day 7]

   Change from baseline in morning pre-dose FEV1 (average of 60- and 30-minute pre-dose values on Day 7)

6. FEV1 Through 6 Hours [Day 7]

   Peak change from baseline in FEV1 through 6 hours

7. Peak Change From Baseline in IC [Day 7]

   Peak change from baseline in inspiratory capacity (IC) (mean of 1 and 2 hours post-dose minus baseline)

8. Mean Evening Trough FEV1 [Day 7]

   Change from baseline in mean evening 12-hour post-dose trough FEV1

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 (or CT scan) 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	Rancho Mirage	California	United States
2	Pearl Investigative Site	Colorado Springs	Colorado	United States
3	Pearl Investigative Site	Waterbury	Connecticut	United States
4	Pearl Investigative Site	Clearwater	Florida	United States
5	Pearl Investigative Site	Pensacola	Florida	United States
6	Pearl Investigative Site	Stockbridge	Georgia	United States
7	Pearl Investigative Site	Minneapolis	Minnesota	United States
8	Pearl Investigative Site	Brooklyn	New York	United States
9	Pearl Investigative Site	Charlotte	North Carolina	United States
10	Pearl Investigative Site	Winston-Salem	North Carolina	United States
11	Pearl Investigative Site	Cincinnati	Ohio	United States
12	Pearl Investigative Site	Medford	Oregon	United States
13	Pearl Investigative Site	Spartanburg	South Carolina	United States

Sponsors and Collaborators

• Pearl Therapeutics, Inc.

Investigators

• Study Director: Colin Reisner, M.D., Pearl Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pearl Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01349816
• Other Study ID Numbers: PT003004
• First Posted: May 9, 2011
• Last Update Posted: Apr 27, 2017
• Last Verified: Apr 1, 2017

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

Study Results

Participant Flow

Recruitment Details	Conducted at 14 US sites from July-November 2011. Entire study period of study participation was a maximum of 9 weeks.
Pre-assignment Detail	Study was a chronic dosing study; each participant received 2 of 6 possible treatments; each treatment period was separated by a washout period of at least 7 days. Patients were randomized into one of 30 treatment sequences. Each sequence included exactly 2 of the 6 treatment groups for this study.

Arm/Group Title	Overall Study
Arm/Group Description	Overall Study
Period Title: Overall Study
STARTED	185
GP MDI 36 µg	61
GFF MDI 36/7.2 µg	58
GFF MDI 36/9.6 µg	56
GFF MDI 18/9.6 µg	57
GFF MDI 9/9.6 µg	57
FF MDI 9.6 µg	61
COMPLETED	155
NOT COMPLETED	30

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	All patients randomized and treated
Overall Participants	185
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.1 (9.18)
Sex: Female, Male (Count of Participants)
Female	78 42.2%
Male	107 57.8%

Outcome Measures

1. Primary Outcome

Title	FEV1 AUC0-12
Description	Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 relative to baseline following chronic dosing (1 week).
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat (MITT) Population is made of participants who completed both treatment periods and had Pre-dose Day 1 data for both and no protocol deviations believed to have a potential impact on efficacy results. Subjects must have had data for the given endpoint to be included.

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	49	42	44	50	49	50
Least Squares Mean (95% Confidence Interval) [Liters]	1.467	1.462	1.493	1.499	1.399	1.465

2. Secondary Outcome

Title	Peak Change From Baseline in FEV1
Description	Peak change from baseline in FEV1 through 2 hours
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	49	43	45	52	51	51
Least Squares Mean (95% Confidence Interval) [Liters]	0.312	0.308	0.344	0.350	0.248	0.307

3. Secondary Outcome

Title	Time to Onset of Action
Description	At least 10% improvement in mean FEV1
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	50	43	45	52	51	51
15 minutes	28 15.1%	21 NaN	20 NaN	30 NaN	15 NaN	24 NaN
30 minutes	10 5.4%	9 NaN	8 NaN	8 NaN	14 NaN	14 NaN
1 hour	4 2.2%	3 NaN	9 NaN	5 NaN	7 NaN	6 NaN
2 hours	4 2.2%	2 NaN	2 NaN	3 NaN	3 NaN	2 NaN
No onset within 2 hours	4 2.2%	8 NaN	6 NaN	6 NaN	12 NaN	5 NaN

4. Secondary Outcome

Title	At Least 12% Improvement in FEV1
Description	Proportion of subjects achieving >=12% improvement in FEV1 relative to baseline
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	50	43	45	52	51	51
15 minutes	22 11.9%	17 NaN	18 NaN	27 NaN	13 NaN	22 NaN
30 minutes	14 7.6%	10 NaN	8 NaN	7 NaN	12 NaN	10 NaN
1 hour	2 1.1%	5 NaN	6 NaN	4 NaN	5 NaN	7 NaN
2 hours	2 1.1%	3 NaN	5 NaN	6 NaN	4 NaN	5 NaN
No onset within 2 hours	10 5.4%	8 NaN	8 NaN	8 NaN	17 NaN	7 NaN

5. Secondary Outcome

Title	Peak Change in IC
Description	Mean inspiratory capacity (IC) of 1 and 2 hours post-dose minus baseline
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	48	43	45	52	51	51
Least Squares Mean (95% Confidence Interval) [Liters]	0.323	0.242	0.339	0.326	0.228	0.316

6. Secondary Outcome

Title	Morning Pre-dose FEV1
Description	Change from baseline in morning pre-dose FEV1 (average of 60- and 30-minute pre-dose values on Day 7)
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	49	43	45	52	51	51
Least Squares Mean (95% Confidence Interval) [Liters]	0.152	0.110	0.122	0.131	0.100	0.103

7. Secondary Outcome

Title	FEV1 Through 6 Hours
Description	Peak change from baseline in FEV1 through 6 hours
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	50	42	45	51	51	51
Least Squares Mean (95% Confidence Interval) [Liters]	0.362	0.356	0.388	0.415	0.283	0.355

8. Secondary Outcome

Title	Peak Change From Baseline in IC
Description	Peak change from baseline in inspiratory capacity (IC) (mean of 1 and 2 hours post-dose minus baseline)
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	48	43	45	52	51	51
Least Squares Mean (95% Confidence Interval) [Liters]	0.333	0.267	0.340	0.351	0.228	0.354

9. Secondary Outcome

Title	Mean Evening Trough FEV1
Description	Change from baseline in mean evening 12-hour post-dose trough FEV1
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	GFF MDI 36/7.2 µg	GFF MDI 36/9.6 µg	GFF MDI 18/9.6 µg	GFF MDI 9/9.6 µg	GP MDI 36 µg	FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID	GFF MDI 36/9.6 µg BID	GFF MDI 18/9.6 µg BID	GFF MDI 9/9.6 µg BID	GP MDI 36 µg BID	FF MDI 9.6 µg BID
Measure Participants	48	43	44	51	49	50
Least Squares Mean (95% Confidence Interval) [Liters]	0.080	0.073	0.105	0.112	0.081	0.120

Adverse Events

Time Frame	Adverse events were collected from the time the subject signed consent up to the follow-up (Final) visit or premature discontinuation visit.
Adverse Event Reporting Description	Safety population included all participants who received at least one dose of study drug, with safety data available. Serious adverse events were collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Arm/Group Title	GFF MDI 36/7.2 µg		GFF MDI 36/9.6 µg		GFF MDI 18/9.6 µg		GFF MDI 9/9.6 µg		GP MDI 36 µg		FF MDI 9.6 µg
Arm/Group Description	GFF MDI 36/7.2 µg BID		GFF MDI 36/9.6 µg BID		GFF MDI 18/9.6 µg BID		GFF MDI 9/9.6 µg BID		GP MDI 36 µg BID		FF MDI 9.6 µg BID
All Cause Mortality
	GFF MDI 36/7.2 µg		GFF MDI 36/9.6 µg		GFF MDI 18/9.6 µg		GFF MDI 9/9.6 µg		GP MDI 36 µg		FF MDI 9.6 µg
	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)
Serious Adverse Events
	GFF MDI 36/7.2 µg		GFF MDI 36/9.6 µg		GFF MDI 18/9.6 µg		GFF MDI 9/9.6 µg		GP MDI 36 µg		FF MDI 9.6 µg
	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	1/58 (1.7%)		0/56 (0%)		0/57 (0%)		0/57 (0%)		2/61 (3.3%)		0/61 (0%)
Infections and infestations
Pyelonephritis	0/58 (0%)	0	0/56 (0%)	0	0/57 (0%)	0	0/57 (0%)	0	1/61 (1.6%)	1	0/61 (0%)	0
Metabolism and nutrition disorders
Hypokalemia	1/58 (1.7%)	1	0/56 (0%)	0	0/57 (0%)	0	0/57 (0%)	0	0/61 (0%)	0	0/61 (0%)	0
Renal and urinary disorders
Renal failure acute	0/58 (0%)	0	0/56 (0%)	0	0/57 (0%)	0	0/57 (0%)	0	1/61 (1.6%)	1	0/61 (0%)	0
Other (Not Including Serious) Adverse Events
	GFF MDI 36/7.2 µg		GFF MDI 36/9.6 µg		GFF MDI 18/9.6 µg		GFF MDI 9/9.6 µg		GP MDI 36 µg		FF MDI 9.6 µg
	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	9/58 (15.5%)		4/56 (7.1%)		1/57 (1.8%)		7/57 (12.3%)		2/61 (3.3%)		8/61 (13.1%)
Gastrointestinal disorders
Dry mouth	3/58 (5.2%)	3	3/56 (5.4%)	3	1/57 (1.8%)	1	5/57 (8.8%)	5	2/61 (3.3%)	2	4/61 (6.6%)	4
Nervous system disorders
Tremor	2/58 (3.4%)	3	0/56 (0%)	0	0/57 (0%)	0	2/57 (3.5%)	2	0/61 (0%)	0	4/61 (6.6%)	4
Headache	4/58 (6.9%)	4	1/56 (1.8%)	1	0/57 (0%)	0	0/57 (0%)	0	0/61 (0%)	0	0/61 (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.