Trial Outcomes & Findings for A Phase 2 Study of MP-376 to Prevent Acute Exacerbations in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT00739648)
NCT ID: NCT00739648
Last Updated: 2024-12-27
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
322 participants
Primary outcome timeframe
From randomization to the patients final study visit (up to 12 months)
Results posted on
2024-12-27
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
108
|
214
|
|
Overall Study
COMPLETED
|
82
|
161
|
|
Overall Study
NOT COMPLETED
|
26
|
53
|
Reasons for withdrawal
| Measure |
Placebo
Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles
|
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
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
15
|
|
Overall Study
Withdrawal by Subject
|
13
|
25
|
|
Overall Study
Lost to Follow-up
|
4
|
7
|
|
Overall Study
Death
|
2
|
0
|
|
Overall Study
Do not know
|
4
|
6
|
Baseline Characteristics
A Phase 2 Study of MP-376 to Prevent Acute Exacerbations in Chronic Obstructive Pulmonary Disease (COPD) Patients
Baseline characteristics by cohort
| Measure |
Placebo
n=108 Participants
Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles
|
MP-376 240 mg BID
n=214 Participants
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
|
Total
n=322 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.4 years
STANDARD_DEVIATION 9.06 • n=5 Participants
|
64.0 years
STANDARD_DEVIATION 9.14 • n=7 Participants
|
63.8 years
STANDARD_DEVIATION 9.10 • n=5 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
153 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
56 Participants
n=5 Participants
|
113 Participants
n=7 Participants
|
169 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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)
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.
Outcome measures
| Measure |
Placebo
n=108 Participants
Placebo inhaled twice daily (BID) via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
|
MP-376 240 mg BID
n=214 Participants
MP-376 240 mg inhaled twice daily (BID)via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
|
|---|---|---|
|
Exacerbation Rate
|
1.20 exacerbation per patient year
Standard Error 0.15
|
1.31 exacerbation per patient year
Standard Error 0.11
|
SECONDARY outcome
Timeframe: from randomization to the patient's final study visit (up to 12 months)Population: MITT
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
Outcome measures
| Measure |
Placebo
n=108 Participants
Placebo inhaled twice daily (BID) via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
|
MP-376 240 mg BID
n=214 Participants
MP-376 240 mg inhaled twice daily (BID)via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
|
|---|---|---|
|
Duration of Acute Exacerbation
|
12.9 Days
Standard Deviation 12.11
|
11.6 Days
Standard Deviation 7.98
|
SECONDARY outcome
Timeframe: from baseline to the conclusion of the fourth 28-day treatment cycle (4 months)Population: MITT
The percent change in the amount of air a patient can inhale
Outcome measures
| Measure |
Placebo
n=108 Participants
Placebo inhaled twice daily (BID) via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
|
MP-376 240 mg BID
n=214 Participants
MP-376 240 mg inhaled twice daily (BID)via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
|
|---|---|---|
|
Percent Change in Forced Vital Capacity (FVC)
|
14.46 Percent
Standard Error 6.18
|
-0.77 Percent
Standard Error 4.43
|
SECONDARY outcome
Timeframe: from baseline to the conclusion of the fourth 28-day treatment cycle (4 months)Population: MITT
The percent change in the amount of air a patient can exhale in 1 second
Outcome measures
| Measure |
Placebo
n=108 Participants
Placebo inhaled twice daily (BID) via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
|
MP-376 240 mg BID
n=214 Participants
MP-376 240 mg inhaled twice daily (BID)via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
|
|---|---|---|
|
Percent Change in Forced Expiratory Volume in 1 Second (FEV1)
|
14.76 Percent
Standard Error 6.21
|
2.42 Percent
Standard Error 4.45
|
Adverse Events
Placebo
Serious events: 32 serious events
Other events: 94 other events
Deaths: 0 deaths
MP-376 240 mg BID
Serious events: 72 serious events
Other events: 197 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=108 participants at risk
Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles
|
MP-376 240 mg BID
n=214 participants at risk
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
|
|---|---|---|
|
General disorders
Condition Aggravated
|
20.4%
22/108 • Number of events 31 • 1 year
|
18.2%
39/214 • Number of events 53 • 1 year
|
|
General disorders
Chest pain
|
2.8%
3/108 • Number of events 4 • 1 year
|
1.9%
4/214 • Number of events 4 • 1 year
|
|
General disorders
Catheter site hematoma
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
General disorders
Multi-organ failure
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
General disorders
Edema
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Infections and infestations
Pneumonia
|
0.93%
1/108 • Number of events 1 • 1 year
|
4.7%
10/214 • Number of events 10 • 1 year
|
|
Infections and infestations
Cellulitis
|
0.00%
0/108 • 1 year
|
0.93%
2/214 • Number of events 2 • 1 year
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/108 • 1 year
|
0.93%
2/214 • Number of events 2 • 1 year
|
|
Infections and infestations
Septic shock
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Infections and infestations
Bursitis infective staphylococcal
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Infections and infestations
Hepatitis C
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Infections and infestations
Herpes zoster
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Infections and infestations
Kidney infection
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Infections and infestations
Nocardiosis
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Infections and infestations
Staphylococcal bacteremia
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Infections and infestations
Streptococcal bacteremia
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/108 • 1 year
|
1.4%
3/214 • Number of events 3 • 1 year
|
|
Cardiac disorders
Atrial fibrillation
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Cardiac disorders
Myocardial infarction
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Cardiac disorders
Atrial tachycardia
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Cardiac disorders
Cardiac failure
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Cardiac disorders
Stress cardiomyopathy
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Cardiac disorders
Tachyarrhythmia
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.9%
2/108 • Number of events 2 • 1 year
|
1.9%
4/214 • Number of events 4 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/108 • 1 year
|
0.93%
2/214 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory depression
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Vascular disorders
Aoritic stenosis
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Vascular disorders
Hypertension
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Vascular disorders
Hypertensive emergency
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Vascular disorders
Hypotension
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Vascular disorders
Malignant hypertension
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Vascular disorders
Peripheral vascular disorder
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Vascular disorders
Venous thrombosis limb
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Gastrointestinal disorders
Pancreatitis
|
0.93%
1/108 • Number of events 2 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Gastritis
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Upper gsatrointestinal hemorrhage
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Nervous system disorders
Syncope
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Nervous system disorders
Dementia
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Nervous system disorders
Paresis
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Psychiatric disorders
Alcohol withdrawal syndrome
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Psychiatric disorders
Depression
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 2 • 1 year
|
|
Psychiatric disorders
Mental status change
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Post procedureal hematoma
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/108 • 1 year
|
0.93%
2/214 • Number of events 2 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Hepatobiliary disorders
Cholecystitits
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Renal failure acute
|
0.93%
1/108 • Number of events 1 • 1 year
|
0.00%
0/214 • 1 year
|
|
Reproductive system and breast disorders
Vaginal prolapse
|
0.00%
0/108 • 1 year
|
0.47%
1/214 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Placebo
n=108 participants at risk
Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles
|
MP-376 240 mg BID
n=214 participants at risk
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
|
|---|---|---|
|
General disorders
Condition aggravated
|
53.7%
58/108 • Number of events 120 • 1 year
|
53.3%
114/214 • Number of events 247 • 1 year
|
|
General disorders
Edema peripheral
|
6.5%
7/108 • Number of events 8 • 1 year
|
7.5%
16/214 • Number of events 16 • 1 year
|
|
General disorders
Chest pain
|
5.6%
6/108 • Number of events 7 • 1 year
|
6.1%
13/214 • Number of events 14 • 1 year
|
|
General disorders
Chest discomfort
|
5.6%
6/108 • Number of events 6 • 1 year
|
5.1%
11/214 • Number of events 11 • 1 year
|
|
Infections and infestations
Sinusititis
|
12.0%
13/108 • Number of events 13 • 1 year
|
5.1%
11/214 • Number of events 13 • 1 year
|
|
Infections and infestations
Pneumonia
|
4.6%
5/108 • Number of events 6 • 1 year
|
7.9%
17/214 • Number of events 24 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
7.4%
8/108 • Number of events 10 • 1 year
|
4.7%
10/214 • Number of events 11 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspenea
|
16.7%
18/108 • Number of events 21 • 1 year
|
13.6%
29/214 • Number of events 42 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.1%
12/108 • Number of events 16 • 1 year
|
11.2%
24/214 • Number of events 25 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
5.6%
6/108 • Number of events 6 • 1 year
|
4.2%
9/214 • Number of events 9 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pharynlaryngeal pain
|
5.6%
6/108 • Number of events 6 • 1 year
|
3.7%
8/214 • Number of events 8 • 1 year
|
|
Nervous system disorders
Dysgeusia
|
2.8%
3/108 • Number of events 3 • 1 year
|
29.0%
62/214 • Number of events 91 • 1 year
|
|
Nervous system disorders
Headache
|
10.2%
11/108 • Number of events 11 • 1 year
|
7.5%
16/214 • Number of events 18 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
12.0%
13/108 • Number of events 113 • 1 year
|
11.2%
24/214 • Number of events 28 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
6.5%
7/108 • Number of events 7 • 1 year
|
6.1%
13/214 • Number of events 14 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
2.8%
3/108 • Number of events 3 • 1 year
|
5.1%
11/214 • Number of events 12 • 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.7%
4/108 • Number of events 4 • 1 year
|
5.6%
12/214 • Number of events 18 • 1 year
|
|
Psychiatric disorders
Insomnia
|
5.6%
6/108 • Number of events 6 • 1 year
|
6.5%
14/214 • Number of events 15 • 1 year
|
|
Psychiatric disorders
Anxiety
|
5.6%
6/108 • Number of events 6 • 1 year
|
2.8%
6/214 • Number of events 6 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place