Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Patients
Brief summary
Patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from frequent and recurrent acute exacerbations (AECB) which are associated with enormous healthcare expenditures and significant morbidity, specifically an increased risk of death, a decline in pulmonary function and a significant change in quality of life. Bacteria appear to have an important role in acute exacerbations in chronic bronchitis and COPD. Studies of acute exacerbations in COPD have shown a reduction in bacterial load with prolonged exacerbation-free interval. In addition, recent studies indicate that acquisition of a new strain of H. influenzae, M. catarrhalis, S. pneumoniae or P. aeruginosa are responsible for many of these exacerbations. Chronic inflammation and bacterial infection predispose many patients to frequent and recurrent acute exacerbations. Mpex believes that intermittent administration of inhaled MP-376 in high risk patients will decrease the incidence of acute exacerbations by both by lowering the organism burden, and resultant inflammation, as well as pre-emptive eradication of any newly acquired bacterial strains.
Detailed description
This study will be a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of MP-376 inhalation solution given daily for 5 days in a 28 day treatment cycle to COPD patients. Study with completed results acquired from Horizon in 2024.
Interventions
DRUGMP-376
MP-376 administered via inhalation for 5 consecutive days within 28-day treatment cycles for up to 12 cycles
DRUGPlacebo
same frequency as study drug using the same method of delivery
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(selected): * \> 40 years of age * History of COPD * Forced expiratory volume in 1 second (FEV1) \</= 70% of predicted and FEV1/Forced vital capacity (FVC) \</= 0.7 value at screening * Have at least two acute exacerbation episodes in the proceeding year * Clinically stable with no changes in health status within the last 30 days * Lifetime smoking history of at least 10 pack-years * Willing and able to use a daily electronic diary
Exclusion criteria
(selected): * Use of any systemic or inhaled antibiotics within 30 days prior to baseline * History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication * Creatinine clearance \< 40 mg/ml/min, AST, ALT \>/= 5 x upper limit of normal (ULN) or total bilirubin \>/= 3 x ULN at Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exacerbation Rate | From randomization to the patients final study visit (up to 12 months) | The number of acute exacerbations per patient-year of study participation, where an acute exacerbation was defined as a deterioration in respiratory symptoms that required treatment with antibiotics, corticosteroids, hospitalization or a combination of those treatments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Forced Vital Capacity (FVC) | from baseline to the conclusion of the fourth 28-day treatment cycle (4 months) | The percent change in the amount of air a patient can inhale |
| Duration of Acute Exacerbation | from randomization to the patient's final study visit (up to 12 months) | From the beginning of antibiotics and/or systemic corticosteroids to the end of antibiotics and/or systemic corticosteroids, whichever was longer, for treatment of the first acute exacerbation |
| Percent Change in Forced Expiratory Volume in 1 Second (FEV1) | from baseline to the conclusion of the fourth 28-day treatment cycle (4 months) | The percent change in the amount of air a patient can exhale in 1 second |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles | 108 |
| MP-376 240 mg BID MP-376 240 mg inhaled twice daily via the PARI eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles | 214 |
| Total | 322 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 15 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Do not know | 4 | 6 |
| Overall Study | Lost to Follow-up | 4 | 7 |
| Overall Study | Withdrawal by Subject | 13 | 25 |
Baseline characteristics
| Characteristic | Placebo | MP-376 240 mg BID | Total |
|---|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 9.06 | 64.0 years STANDARD_DEVIATION 9.14 | 63.8 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 52 Participants | 101 Participants | 153 Participants |
| Sex: Female, Male Male | 56 Participants | 113 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 94 / 108 | 197 / 214 |
| serious Total, serious adverse events | 32 / 108 | 72 / 214 |
Outcome results
Primary
Exacerbation Rate
The number of acute exacerbations per patient-year of study participation, where an acute exacerbation was defined as a deterioration in respiratory symptoms that required treatment with antibiotics, corticosteroids, hospitalization or a combination of those treatments.
Time frame: From randomization to the patients final study visit (up to 12 months)
Population: modified intent to treat (MITT; patients who received at least one dose of study drug)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Exacerbation Rate | 1.20 exacerbation per patient year | Standard Error 0.15 |
| MP-376 240 mg BID | Exacerbation Rate | 1.31 exacerbation per patient year | Standard Error 0.11 |
p-value: 0.728290% CI: [0.86, 1.39]Regression, Linear
Secondary
Duration of Acute Exacerbation
From the beginning of antibiotics and/or systemic corticosteroids to the end of antibiotics and/or systemic corticosteroids, whichever was longer, for treatment of the first acute exacerbation
Time frame: from randomization to the patient's final study visit (up to 12 months)
Population: MITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Duration of Acute Exacerbation | 12.9 Days | Standard Deviation 12.11 |
| MP-376 240 mg BID | Duration of Acute Exacerbation | 11.6 Days | Standard Deviation 7.98 |
Secondary
Percent Change in Forced Expiratory Volume in 1 Second (FEV1)
The percent change in the amount of air a patient can exhale in 1 second
Time frame: from baseline to the conclusion of the fourth 28-day treatment cycle (4 months)
Population: MITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Forced Expiratory Volume in 1 Second (FEV1) | 14.76 Percent | Standard Error 6.21 |
| MP-376 240 mg BID | Percent Change in Forced Expiratory Volume in 1 Second (FEV1) | 2.42 Percent | Standard Error 4.45 |
p-value: 0.946490% CI: [-24.9, 0.26]Mixed Models Analysis
Secondary
Percent Change in Forced Vital Capacity (FVC)
The percent change in the amount of air a patient can inhale
Time frame: from baseline to the conclusion of the fourth 28-day treatment cycle (4 months)
Population: MITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Forced Vital Capacity (FVC) | 14.46 Percent | Standard Error 6.18 |
| MP-376 240 mg BID | Percent Change in Forced Vital Capacity (FVC) | -0.77 Percent | Standard Error 4.43 |
p-value: 0.976890% CI: [-27.8, -2.66]Mixed Models Analysis