Study to Assess the Safety and Tolerability of PT010, PT009 and PT003 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

• Sponsor: Pearl Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02536508
• Collaborator: (none)
• Enrollment: 627
• Locations: 64
• Arms: 3
• Actual Duration (Months): 25.1
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Study to Assess the Safety and Tolerability of PT010, PT009 and PT003 in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Condition or Disease	Intervention/Treatment	Phase
COPD	Drug: BGF MDI 320/14.4/9.6 μg; Drug: GFF MDI 14.4/9.6 μg; Drug: BFF MDI 320/9.6 μg	Phase 3

Detailed Description

A Randomized, Double-Blind, Parallel-Group, 52-Week, Chronic-Dosing, Multi-Center Study to Assess the Safety and Tolerability of PT010, PT009 and PT003 in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Study Design

• Study Type: Interventional
• Actual Enrollment: 627 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double-Blind
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel-Group, 52-Week, Chronic-Dosing, Multi-Center Study to Assess the Safety and Tolerability of PT010, PT009 and PT003 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease
• Actual Study Start Date: Aug 10, 2015
• Actual Primary Completion Date: Sep 12, 2017
• Actual Study Completion Date: Sep 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BGF MDI (PT010) 320/14.4/9.6 μg Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) metered dose inhaler (MDI) (PT010, BGF MDI)	Drug: BGF MDI 320/14.4/9.6 μg; Budesonide, Glycopyrronium, and Formoterol Fumarate; Other Names: BGF MDI
Experimental: GFF MDI (PT003) 14.4/9.6 μg Glycopyrronium and Formoterol Fumarate (GFF) metered dose inhaler (MDI) (PT003, GFF MDI)	Drug: GFF MDI 14.4/9.6 μg; Glycopyrronium and Formoterol Fumarate; Other Names: GFF MDI
Experimental: BFF MDI (PT009) 320/9.6 μg Budesonide and Formoterol Fumarate (BFF) metered dose inhaler (MDI) (PT009, BFF MDI)	Drug: BFF MDI 320/9.6 μg; Budesonide and Formoterol Fumarate; Other Names: BFF MDI

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in BMD of the Lumbar Spine [at week 52]

   Percent change from baseline in BMD of the lumbar spine T-Score at Week 52.

2. Change From Baseline in the LOCS III (P) Score at Week 52 [at week 52]

   Change from baseline in the LOCS III (P) score (Severity of Posterior Subcapsular Cataract) at Week 52. P score is reported as a decimalized scale ranging from 0.1 (indicating a completely clear or colorless lens) to 5.9 (indicating complete opacification on the posterior capsule). A negative change in P score indicates an improvement and a positive change indicates a deterioration of LOCS III. A change in P score within 0.5 is an acceptable variation margin.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Given their signed written informed consent to participate. Must have agreed to participate in and complete the lead-in Study PT010006.(NCT02497001)

Exclusion Criteria:

Severe osteoporosis Unable to achieve an acceptable DEXA scan Inability to achieve pupil dilation to at least 6 mm Subjects with an implanted artificial intraocular lens or are scheduled to undergo cataract surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Dothan	Alabama	United States	36303
2	Research Site	Jasper	Alabama	United States	35501
3	Research Site	Peoria	Arizona	United States	85381
4	Research Site	Phoenix	Arizona	United States	85018
5	Research Site	Fullerton	California	United States	92835
6	Research Site	Gold River	California	United States	95670
7	Research Site	Poway	California	United States	92064
8	Research Site	Rolling Hills Estates	California	United States	90274
9	Research Site	Sacramento	California	United States	95821
10	Research Site	Clearwater	Florida	United States	33756
11	Research Site	Miami	Florida	United States	33186
12	Research Site	Ormond Beach	Florida	United States	32174
13	Research Site	Pensacola	Florida	United States	32503
14	Research Site	Tamarac	Florida	United States	33321
15	Research Site	Tampa	Florida	United States	33603
16	Research Site	Winter Park	Florida	United States	32789
17	Research Site	Dacula	Georgia	United States	30019
18	Research Site	Norcross	Georgia	United States	30071
19	Research Site	Rincon	Georgia	United States	31326
20	Research Site	Edina	Minnesota	United States	55435
21	Research Site	Minneapolis	Minnesota	United States	55402
22	Research Site	Minneapolis	Minnesota	United States	55407
23	Research Site	Woodbury	Minnesota	United States	55125
24	Research Site	Saint Charles	Missouri	United States	63301
25	Research Site	Saint Louis	Missouri	United States	63141
26	Research Site	Las Vegas	Nevada	United States	89106
27	Research Site	Reno	Nevada	United States	89503
28	Research Site	Albuquerque	New Mexico	United States	87108
29	Research Site	Charlotte	North Carolina	United States	28207
30	Research Site	Gastonia	North Carolina	United States	28054
31	Research Site	Greensboro	North Carolina	United States	27408
32	Research Site	Hendersonville	North Carolina	United States	28739
33	Research Site	Mooresville	North Carolina	United States	28117
34	Research Site	Wilmington	North Carolina	United States	28401
35	Research Site	Winston-Salem	North Carolina	United States	27103
36	Research Site	Cincinnati	Ohio	United States	45231
37	Research Site	Cincinnati	Ohio	United States	45242
38	Research Site	Cincinnati	Ohio	United States	45245
39	Research Site	Columbus	Ohio	United States	43213
40	Research Site	Columbus	Ohio	United States	43235
41	Research Site	Dayton	Ohio	United States	45459
42	Research Site	Dublin	Ohio	United States	43016
43	Research Site	Oklahoma City	Oklahoma	United States	73103
44	Research Site	Medford	Oregon	United States	97504
45	Research Site	Anderson	South Carolina	United States	29621
46	Research Site	Charleston	South Carolina	United States	29406
47	Research Site	Easley	South Carolina	United States	29640
48	Research Site	Greenville	South Carolina	United States	29615
49	Research Site	Indian Land	South Carolina	United States	29707
50	Research Site	Mount Pleasant	South Carolina	United States	29464
51	Research Site	Rock Hill	South Carolina	United States	29732
52	Research Site	Seneca	South Carolina	United States	29678
53	Research Site	Spartanburg	South Carolina	United States	29303
54	Research Site	Union	South Carolina	United States	29379
55	Research Site	Johnson City	Tennessee	United States	37601
56	Research Site	Kingwood	Texas	United States	77339
57	Research Site	Longview	Texas	United States	75604
58	Research Site	San Antonio	Texas	United States	78229
59	Research Site	Abingdon	Virginia	United States	24210
60	Research Site	Newport News	Virginia	United States	23606
61	Research Site	Richmond	Virginia	United States	23225
62	Research Site	Richmond	Virginia	United States	23230
63	Research Site	Tacoma	Washington	United States	98405
64	Research Site	Morgantown	West Virginia	United States	26505

Sponsors and Collaborators

• Pearl Therapeutics, Inc.

Investigators

• Study Director: Colin Reisner, Pearl Therapeutics
• Study Director: Paul Dorinsky, MD, Pearl Therapeutics

Study Documents (Full-Text)

• Study Protocol - Mar 18, 2016
• Statistical Analysis Plan - Jul 17, 2017

More Information

Additional Information:

• PT010008-01_Protocol_Version_2.0_REDACTED.pdf

Publications

None provided.

• Responsible Party: Pearl Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02536508
• Other Study ID Numbers: PT010008; NCT03313570
• First Posted: Sep 1, 2015
• Last Update Posted: Feb 26, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details	The study randomized subjects at 69 sites in the United States from September 2015 to September 2017. The entire study period was scheduled to take up to approximately 58 weeks for each individual subject from the time of screening through the follow-up period.
Pre-assignment Detail	Subjects were randomized in a 2:2:1 scheme (BGF MDI:GFF MDI:BFF MDI).

Arm/Group Title	BGF MDI 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug	BFF MDI 320/9.6 ug
Arm/Group Description	Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug
Period Title: Overall Study
STARTED	194	174	88
COMPLETED	142	130	65
NOT COMPLETED	52	44	23

Baseline Characteristics

Arm/Group Title	BGF MDI 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug	BFF MDI 320/9.6 ug	Total
Arm/Group Description	Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug	Total of all reporting groups
Overall Participants	194	174	88	456
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.6 (7.9)	62.4 (7.8)	64.0 (7.2)	62.8 (7.7)
Sex: Female, Male (Count of Participants)
Female	92 47.4%	87 50%	35 39.8%	214 46.9%
Male	102 52.6%	87 50%	53 60.2%	242 53.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 4.6%	5 2.9%	6 6.8%	20 4.4%
Not Hispanic or Latino	185 95.4%	169 97.1%	82 93.2%	436 95.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Black	13 6.7%	17 9.8%	9 10.2%	39 8.6%
White	179 92.3%	156 89.7%	79 89.8%	414 90.8%
Asian	0 0%	1 0.6%	0 0%	1 0.2%
Other	2 1%	0 0%	0 0%	2 0.4%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in BMD of the Lumbar Spine
Description	Percent change from baseline in BMD of the lumbar spine T-Score at Week 52.
Time Frame	at week 52

Outcome Measure Data

Analysis Population Description

BMD Population was defined as all evaluable subjects in the Safety Population who had a baseline BMD assessment and at least 1 on-treatment BMD assessment. Subjects were analyzed according to actual study drug received.

Arm/Group Title	BGF MDI 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug	BFF MDI 320/9.6 ug
Arm/Group Description	Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug
Measure Participants	128	123	57
Least Squares Mean (95% Confidence Interval) [Percentage]	-0.093	0.379	-0.120

2. Primary Outcome

Title	Change From Baseline in the LOCS III (P) Score at Week 52
Description	Change from baseline in the LOCS III (P) score (Severity of Posterior Subcapsular Cataract) at Week 52. P score is reported as a decimalized scale ranging from 0.1 (indicating a completely clear or colorless lens) to 5.9 (indicating complete opacification on the posterior capsule). A negative change in P score indicates an improvement and a positive change indicates a deterioration of LOCS III. A change in P score within 0.5 is an acceptable variation margin.
Time Frame	at week 52

Outcome Measure Data

Analysis Population Description

Ophthalmologic Population was defined as all evaluable subjects in the Safety Population who had a baseline ophthalmologic assessment and at least 1 on-treatment ophthalmologic assessment. Subjects were analyzed according to actual study drug received.

Arm/Group Title	BGF MDI 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug	BFF MDI 320/9.6 ug
Arm/Group Description	Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug
Measure Participants	132	125	54
Least Squares Mean (95% Confidence Interval) [P-Score]	0.153	.026	0.022

Adverse Events

Time Frame	Adverse events were collected from the time of administration of the first dose of study drug to the time of the final follow-up telephone call. Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 54 weeks.
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
Arm/Group Description	Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug		Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug		Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/194 (1.5%)		1/174 (0.6%)		0/88 (0%)
Serious Adverse Events
	BGF MDI 320/14.4/9.6 ug		GFF MDI 14.4/9.6 ug		BFF MDI 320/9.6 ug
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/194 (17%)		22/174 (12.6%)		7/88 (8%)
Cardiac disorders
Acute Myocardial Infarction	0/194 (0%)	0	2/174 (1.1%)	2	0/88 (0%)	0
Atrioventricular block complete	1/194 (0.5%)	1	0/174 (0%)	0	1/88 (1.1%)	1
Myocardial Infarction	2/194 (1%)	2	0/174 (0%)	0	0/88 (0%)	0
Acute coronary syndrome	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Angina unstable	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Coronary artery occlusion	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Myocardial ischaemia	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Supraventricular tachycardia	0/194 (0%)	0	0/174 (0%)	0	1/88 (1.1%)	1
Cardiac failure congestive	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Coronary artery disease	0/194 (0%)	0	0/174 (0%)	0	1/88 (1.1%)	1
Eye disorders
Cataract	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Gastrointestinal disorders
Abdominal hernia	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Gastrointestinal haemorrhage	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Inguinal hernia	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Pancreatitis acute	1/194 (0.5%)	1	1/174 (0.6%)	1	0/88 (0%)	0
General disorders
Non-cardiac chest pain	1/194 (0.5%)	1	1/174 (0.6%)	1	0/88 (0%)	0
Hepatobiliary disorders
Cholecystitis acute	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Infections and infestations
Pneumonia	2/194 (1%)	2	4/174 (2.3%)	4	0/88 (0%)	0
Bronchitis	1/194 (0.5%)	1	0/174 (0%)	0	1/88 (1.1%)	2
Gastritis viral	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Upper respiratory tract infection	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Cellulitis	1/194 (0.5%)	1	0/174 (0%)	0	1/88 (1.1%)	2
Sepsis	1/194 (0.5%)	1	0/174 (0%)	0	1/88 (1.1%)	1
Diverticulitis	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Gastroenteritis	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Pyelonephritis acute	0/194 (0%)	0	0/174 (0%)	0	1/88 (1.1%)	1
Urinary tract infection	0/194 (0%)	0	0/174 (0%)	0	1/88 (1.1%)	1
Injury, poisoning and procedural complications
Hip fracture	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Pulmonary contusion	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Rib fracture	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Road traffic accident	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Respiratory fume inhalation disorder	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Investigations
Electrocardiogram T wave invesion	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Intervertebral disc disorder	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Squamous cell carcinoma of lung	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Adenocarcinoma	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Colorectal cancer metastatic	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Metastases to lung	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Nervous system disorders
Syncope	2/194 (1%)	2	0/174 (0%)	0	0/88 (0%)	0
Cerebral infarction	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Psychiatric disorders
Anxiety	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Suicidal ideation	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/194 (0.5%)	2	0/174 (0%)	0	0/88 (0%)	0
Acute kidney injury	0/194 (0%)	0	0/174 (0%)	0	1/88 (1.1%)	1
Reproductive system and breast disorders
Pelvic pain	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic Pulmonary Obstructive Disease	12/194 (6.2%)	13	9/174 (5.2%)	11	2/88 (2.3%)	3
Acute Respiratory Failure	0/194 (0%)	0	2/174 (1.1%)	2	0/88 (0%)	0
Respiratory Failure	1/194 (0.5%)	1	0/174 (0%)	0	1/88 (1.1%)	1
Hypoxia	0/194 (0%)	0	1/174 (0.6%)	2	0/88 (0%)	0
Hypercapnia	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Pneumonia aspiration	1/194 (0.5%)	1	0/174 (0%)	0	0/88 (0%)	0
Pulmonary mass	0/194 (0%)	0	0/174 (0%)	0	1/88 (1.1%)	1
Vascular disorders
Intermittent claudication	0/194 (0%)	0	1/174 (0.6%)	1	0/88 (0%)	0
Peripheral vascular disorder	0/194 (0%)	0	0/174 (0%)	0	1/88 (1.1%)	1
Other (Not Including Serious) Adverse Events
	BGF MDI 320/14.4/9.6 ug		GFF MDI 14.4/9.6 ug		BFF MDI 320/9.6 ug
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/194 (32%)		51/174 (29.3%)		30/88 (34.1%)
Gastrointestinal disorders
Diarrhoea	5/194 (2.6%)	5	9/174 (5.2%)	9	2/88 (2.3%)	2
Infections and infestations
Upper Respiratory Tract Infection	18/194 (9.3%)	24	17/174 (9.8%)	20	6/88 (6.8%)	6
Viral Upper Respiratory Tract Infection	9/194 (4.6%)	11	5/174 (2.9%)	6	6/88 (6.8%)	6
Sinusitis	11/194 (5.7%)	14	6/174 (3.4%)	7	2/88 (2.3%)	3
Urinary Tract Infection	10/194 (5.2%)	10	6/174 (3.4%)	9	4/88 (4.5%)	4
Bronchitis	12/194 (6.2%)	13	8/174 (4.6%)	10	2/88 (2.3%)	2
Musculoskeletal and connective tissue disorders
Muscle Spasms	6/194 (3.1%)	6	2/174 (1.1%)	2	5/88 (5.7%)	5
Respiratory, thoracic and mediastinal disorders
Dysphonia	6/194 (3.1%)	6	2/174 (1.1%)	2	5/88 (5.7%)	5
Dyspnoea	4/194 (2.1%)	4	5/174 (2.9%)	5	5/88 (5.7%)	5

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 it's opinions, or the opinions of the publication committee, if these differ with the proposed publication.