COPD
Conditions
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
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
Interventions
Budesonide, Glycopyrronium, and Formoterol Fumarate
Glycopyrronium and Formoterol Fumarate
Budesonide and Formoterol Fumarate
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-Blind
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
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 details
Subjects were randomized in a 2:2:1 scheme (BGF MDI:GFF MDI:BFF MDI).
Participants by arm
| Arm | Count |
|---|---|
| BGF MDI 320/14.4/9.6 ug Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug | 194 |
| GFF MDI 14.4/9.6 ug Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug | 174 |
| BFF MDI 320/9.6 ug Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug | 88 |
| Total | 456 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative Reasons | 0 | 1 | 0 |
| Overall Study | Adverse Event | 14 | 13 | 6 |
| Overall Study | Lack of Efficacy | 3 | 5 | 4 |
| Overall Study | Lost to Follow-up | 12 | 4 | 0 |
| Overall Study | Major Protocol Deviation | 2 | 2 | 2 |
| Overall Study | Physician Decision | 0 | 4 | 2 |
| Overall Study | Protocol Discontinuation Criteria | 3 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 18 | 13 | 7 |
Baseline characteristics
| Characteristic | BGF MDI 320/14.4/9.6 ug | GFF MDI 14.4/9.6 ug | BFF MDI 320/9.6 ug | Total |
|---|---|---|---|---|
| Age, Continuous | 62.6 Years STANDARD_DEVIATION 7.9 | 62.4 Years STANDARD_DEVIATION 7.8 | 64.0 Years STANDARD_DEVIATION 7.2 | 62.8 Years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 5 Participants | 6 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 185 Participants | 169 Participants | 82 Participants | 436 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 13 Participants | 17 Participants | 9 Participants | 39 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 179 Participants | 156 Participants | 79 Participants | 414 Participants |
| Sex: Female, Male Female | 92 Participants | 87 Participants | 35 Participants | 214 Participants |
| Sex: Female, Male Male | 102 Participants | 87 Participants | 53 Participants | 242 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 194 | 1 / 174 | 0 / 88 |
| other Total, other adverse events | 62 / 194 | 51 / 174 | 30 / 88 |
| serious Total, serious adverse events | 33 / 194 | 22 / 174 | 7 / 88 |
Outcome results
Primary
Change From Baseline in the LOCS III (P) Score 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BGF MDI 320/14.4/9.6 ug | Change From Baseline in the LOCS III (P) Score at Week 52 | 0.153 P-Score |
| GFF MDI 14.4/9.6 ug | Change From Baseline in the LOCS III (P) Score at Week 52 | .026 P-Score |
| BFF MDI 320/9.6 ug | Change From Baseline in the LOCS III (P) Score at Week 52 | 0.022 P-Score |
Primary
Percent Change From Baseline in BMD of the Lumbar Spine
Percent change from baseline in BMD of the lumbar spine T-Score at Week 52.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BGF MDI 320/14.4/9.6 ug | Percent Change From Baseline in BMD of the Lumbar Spine | -0.093 Percentage |
| GFF MDI 14.4/9.6 ug | Percent Change From Baseline in BMD of the Lumbar Spine | 0.379 Percentage |
| BFF MDI 320/9.6 ug | Percent Change From Baseline in BMD of the Lumbar Spine | -0.120 Percentage |