Trial Outcomes & Findings for Study to Assess the Safety and Tolerability of PT010, PT009 and PT003 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (NCT NCT02536508)

NCT ID: NCT02536508

Last Updated: 2021-02-26

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

627 participants

Primary outcome timeframe

at week 52

Results posted on

2021-02-26

Participant Flow

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.

Subjects were randomized in a 2:2:1 scheme (BGF MDI:GFF MDI:BFF MDI).

Participant milestones

Participant milestones
Measure	BGF MDI 320/14.4/9.6 ug Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	BFF MDI 320/9.6 ug Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug
Overall Study STARTED	194	174	88
Overall Study COMPLETED	142	130	65
Overall Study NOT COMPLETED	52	44	23

Reasons for withdrawal

Reasons for withdrawal
Measure	BGF MDI 320/14.4/9.6 ug Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	BFF MDI 320/9.6 ug Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug
Overall Study Withdrawal by Subject	18	13	7
Overall Study Adverse Event	14	13	6
Overall Study Lost to Follow-up	12	4	0
Overall Study Lack of Efficacy	3	5	4
Overall Study Protocol Discontinuation Criteria	3	2	2
Overall Study Physician Decision	0	4	2
Overall Study Major Protocol Deviation	2	2	2
Overall Study Administrative Reasons	0	1	0

Baseline Characteristics

Safety Population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BGF MDI 320/14.4/9.6 ug n=194 Participants Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug n=174 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	BFF MDI 320/9.6 ug n=88 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug	Total n=456 Participants Total of all reporting groups
Age, Continuous	62.6 Years STANDARD_DEVIATION 7.9 • n=5 Participants • Safety Population	62.4 Years STANDARD_DEVIATION 7.8 • n=7 Participants • Safety Population	64.0 Years STANDARD_DEVIATION 7.2 • n=5 Participants • Safety Population	62.8 Years STANDARD_DEVIATION 7.7 • n=4 Participants • Safety Population
Sex: Female, Male Female	92 Participants n=5 Participants • Safety Population	87 Participants n=7 Participants • Safety Population	35 Participants n=5 Participants • Safety Population	214 Participants n=4 Participants • Safety Population
Sex: Female, Male Male	102 Participants n=5 Participants • Safety Population	87 Participants n=7 Participants • Safety Population	53 Participants n=5 Participants • Safety Population	242 Participants n=4 Participants • Safety Population
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants • Safety Population	5 Participants n=7 Participants • Safety Population	6 Participants n=5 Participants • Safety Population	20 Participants n=4 Participants • Safety Population
Ethnicity (NIH/OMB) Not Hispanic or Latino	185 Participants n=5 Participants • Safety Population	169 Participants n=7 Participants • Safety Population	82 Participants n=5 Participants • Safety Population	436 Participants n=4 Participants • Safety Population
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Safety Population	0 Participants n=7 Participants • Safety Population	0 Participants n=5 Participants • Safety Population	0 Participants n=4 Participants • Safety Population
Race/Ethnicity, Customized Black	13 Participants n=5 Participants • Safety Population	17 Participants n=7 Participants • Safety Population	9 Participants n=5 Participants • Safety Population	39 Participants n=4 Participants • Safety Population
Race/Ethnicity, Customized White	179 Participants n=5 Participants • Safety Population	156 Participants n=7 Participants • Safety Population	79 Participants n=5 Participants • Safety Population	414 Participants n=4 Participants • Safety Population
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants • Safety Population	1 Participants n=7 Participants • Safety Population	0 Participants n=5 Participants • Safety Population	1 Participants n=4 Participants • Safety Population
Race/Ethnicity, Customized Other	2 Participants n=5 Participants • Safety Population	0 Participants n=7 Participants • Safety Population	0 Participants n=5 Participants • Safety Population	2 Participants n=4 Participants • Safety Population

PRIMARY outcome

Timeframe: at week 52

Population: 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.

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

Outcome measures

Outcome measures
Measure	BGF MDI 320/14.4/9.6 ug n=128 Participants Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug n=123 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	BFF MDI 320/9.6 ug n=57 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug
Percent Change From Baseline in BMD of the Lumbar Spine	-0.093 Percentage Interval -0.739 to 0.557	0.379 Percentage Interval -0.28 to 1.042	-0.120 Percentage Interval -1.087 to 0.857

PRIMARY outcome

Timeframe: at week 52

Population: 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.

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.

Outcome measures

Outcome measures
Measure	BGF MDI 320/14.4/9.6 ug n=132 Participants Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug n=125 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	BFF MDI 320/9.6 ug n=54 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug
Change From Baseline in the LOCS III (P) Score at Week 52	0.153 P-Score Interval 0.079 to 0.227	.026 P-Score Interval -0.055 to 0.106	0.022 P-Score Interval -0.09 to 0.135

Adverse Events

BGF MDI 320/14.4/9.6 ug

Serious events: 33 serious events

Other events: 62 other events

Deaths: 3 deaths

GFF MDI 14.4/9.6 ug

Serious events: 22 serious events

Other events: 51 other events

Deaths: 1 deaths

BFF MDI 320/9.6 ug

Serious events: 7 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	BGF MDI 320/14.4/9.6 ug n=194 participants at risk Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug n=174 participants at risk Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug	BFF MDI 320/9.6 ug n=88 participants at risk Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug
Infections and infestations Upper Respiratory Tract Infection	9.3% 18/194 • Number of events 24 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	9.8% 17/174 • Number of events 20 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	6.8% 6/88 • Number of events 6 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Viral Upper Respiratory Tract Infection	4.6% 9/194 • Number of events 11 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	2.9% 5/174 • Number of events 6 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	6.8% 6/88 • Number of events 6 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Sinusitis	5.7% 11/194 • Number of events 14 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	3.4% 6/174 • Number of events 7 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	2.3% 2/88 • Number of events 3 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Urinary Tract Infection	5.2% 10/194 • Number of events 10 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	3.4% 6/174 • Number of events 9 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	4.5% 4/88 • Number of events 4 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Bronchitis	6.2% 12/194 • Number of events 13 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	4.6% 8/174 • Number of events 10 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	2.3% 2/88 • Number of events 2 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Dysphonia	3.1% 6/194 • Number of events 6 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	1.1% 2/174 • Number of events 2 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	5.7% 5/88 • Number of events 5 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.1% 4/194 • Number of events 4 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	2.9% 5/174 • Number of events 5 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	5.7% 5/88 • Number of events 5 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Musculoskeletal and connective tissue disorders Muscle Spasms	3.1% 6/194 • Number of events 6 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	1.1% 2/174 • Number of events 2 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	5.7% 5/88 • Number of events 5 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Diarrhoea	2.6% 5/194 • Number of events 5 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	5.2% 9/174 • Number of events 9 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	2.3% 2/88 • Number of events 2 • 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. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.

Additional Information

Pearl Therapeutics, Inc.

Phone: 1-877-240-9479

Email: [email protected]

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