A Phase 2 Study of MP-376 to Prevent Acute Exacerbations... | NCT00739648

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Placebo inhaled twice daily via the PARI eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles	Drug: Placebo
MP-376 240 mg Twice Daily (BID)	Experimental	MP-376 240 mg BID inhaled via the PARI eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles	Drug: MP-376

Name	Type	Description	Arm Group Labels	Other Names
MP-376	Drug	MP-376 administered via inhalation for 5 consecutive days within 28-day treatment cycles for up to 12 cycles	MP-376 240 mg Twice Daily (BID)

Measure	Description	Time Frame
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.	From randomization to the patients final study visit (up to 12 months)

Measure	Description	Time Frame
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	from randomization to the patient's final study visit (up to 12 months)
Percent Change in Forced Vital Capacity (FVC)

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Haleyville	Alabama	35565	United States

PubMed Identifier	Type	Citation	Retractions
25287629	Derived	Leidy NK, Murray LT, Monz BU, Nelsen L, Goldman M, Jones PW, Dansie EJ, Sethi S. Measuring respiratory symptoms of COPD: performance of the EXACT- Respiratory Symptoms Tool (E-RS) in three clinical trials. Respir Res. 2014 Oct 7;15(1):124. doi: 10.1186/s12931-014-0124-z.
24432712	Derived	Leidy NK, Murray LT, Jones P, Sethi S. Performance of the EXAcerbations of chronic pulmonary disease tool patient-reported outcome measure in three clinical trials of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014 Mar;11(3):316-25. doi: 10.1513/AnnalsATS.201309-305OC.

ID	Title	Description
FG000	Placebo	Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles
FG001	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

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

modified intent to treat (MITT; patients who received at least one dose of study drug)

Posted

Mean

Standard Error

exacerbation per patient year

From randomization to the patients final study visit (up to 12 months)

ID	Title	Description
OG000	Placebo	Placebo inhaled twice daily (BID) via PARI eFlow nebulizer for 5 consecutive days in each 28-day treatment cycle for up to 12 cycles
OG001	MP-376 240 mg BID	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

Units	Counts
Participants	OG000108 OG001214

Title

Denominators

Categories

Title	Measurements
	OG0001.20± 0.15 OG0011.31± 0.11

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear	negative binomial regression model	0.7282		Odds Ratio (OR)	1.09			2-Sided	90	0.86	1.39					Superiority or Other (legacy)

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

MITT

Posted

Mean

Standard Deviation

Days

from randomization to the patient's final study visit (up to 12 months)

ID	Title	Description
OG000	Placebo	Placebo inhaled BID via nebulization for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles
OG001	MP-376 240 mg BID	MP-376 240 mg inhaled BID via nebulization for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles

Units	Counts
Participants	OG000

Secondary

Percent Change in Forced Vital Capacity (FVC)

The percent change in the amount of air a patient can inhale

MITT

Posted

Least Squares Mean

Standard Error

Percent

from baseline to the conclusion of the fourth 28-day treatment cycle (4 months)

ID	Title	Description
OG000	Placebo	Placebo inhaled BID via nebulization for 5 consecutive days in a 28-day cycle for up to 12 cycles
OG001	MP-376 240 mg BID	MP-376 240 mg inhaled BID via nebulization for 5 consecutive days in a 28-day cycle for up to 12 cycles

Units	Counts
Participants	OG000

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

MITT

Posted

Least Squares Mean

Standard Error

Percent

from baseline to the conclusion of the fourth 28-day treatment cycle (4 months)

ID	Title	Description
OG000	Placebo	Placebo inhaled BID via nebulization for 5 consecutive days in a 28-day cycle for up to 12 cycles
OG001	MP-376 240 mg BID	MP-376 240 mg inhaled BID via nebulization for 5 consecutive days in a 28-day cycle for up to 12 cycles

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Condition Aggravated	General disorders	MedDRA (10.0)	Systematic Assessment	Pulmonary exacerbation	EG00031 events22 affected108 at risk EG00153 events39 affected214 at risk
Chest pain	General disorders	MedDRA (10.0)	Systematic Assessment		EG0004 events3 affected108 at risk EG0014 events4 affected214 at risk
Catheter site hematoma	General disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Multi-organ failure	General disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Non-cardiac chest pain	General disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Edema	General disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Pneumonia	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG00110 events10 affected214 at risk
Cellulitis	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0012 events2 affected214 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0012 events2 affected214 at risk
Septic shock	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0011 events1 affected214 at risk
Bursitis infective staphylococcal	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Gastroenteritis	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Hepatitis C	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Herpes zoster	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Kidney infection	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Nocardiosis	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Staphylococcal bacteremia	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Streptococcal bacteremia	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Coronary artery disease	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0013 events3 affected214 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0011 events1 affected214 at risk
Myocardial infarction	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0011 events1 affected214 at risk
Angina pectoris	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Angina unstable	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Atrial tachycardia	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Cardiac failure	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Stress cardiomyopathy	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment		EG0002 events2 affected108 at risk EG0014 events4 affected214 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0011 events1 affected214 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0012 events2 affected214 at risk
Respiratory depression	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Aoritic stenosis	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Hypertension	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Hypertensive crisis	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Hypertensive emergency	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Hypotension	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Malignant hypertension	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Venous thrombosis limb	Vascular disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0002 events1 affected108 at risk EG0011 events1 affected214 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Gastritis	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Ileus	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Upper gsatrointestinal hemorrhage	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Syncope	Nervous system disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0011 events1 affected214 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Dementia	Nervous system disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Paresis	Nervous system disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Confusional state	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Depression	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0012 events1 affected214 at risk
Mental status change	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Post procedureal hematoma	Injury, poisoning and procedural complications	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0012 events2 affected214 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Anemia	Blood and lymphatic system disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Cholecystitits	Hepatobiliary disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (10.0)	Systematic Assessment		EG0001 events1 affected108 at risk EG0010 events0 affected214 at risk
Vaginal prolapse	Reproductive system and breast disorders	MedDRA (10.0)	Systematic Assessment		EG0000 events0 affected108 at risk EG0011 events1 affected214 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Condition aggravated	General disorders	MedDRA (10.0)	Systematic Assessment	Pulmonary exacerbation	EG000120 events58 affected108 at risk EG001247 events114 affected214 at risk
Edema peripheral	General disorders	MedDRA (10.0)	Systematic Assessment		EG0008 events7 affected108 at risk EG00116 events16 affected214 at risk
Chest pain	General disorders	MedDRA (10.0)	Systematic Assessment		EG0007 events6 affected108 at risk EG00114 events13 affected214 at risk
Chest discomfort	General disorders	MedDRA (10.0)	Systematic Assessment		EG0006 events6 affected108 at risk EG00111 events11 affected214 at risk
Sinusititis	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG00013 events13 affected108 at risk EG00113 events11 affected214 at risk
Pneumonia	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG0006 events5 affected108 at risk EG00124 events17 affected214 at risk
Urinary tract infection	Infections and infestations	MedDRA (10.0)	Systematic Assessment		EG00010 events8 affected108 at risk EG00111 events10 affected214 at risk
Dyspenea	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment		EG00021 events18 affected108 at risk EG00142 events29 affected214 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment		EG00016 events12 affected108 at risk EG00125 events24 affected214 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment		EG0006 events6 affected108 at risk EG0019 events9 affected214 at risk
Pharynlaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment		EG0006 events6 affected108 at risk EG0018 events8 affected214 at risk
Dysgeusia	Nervous system disorders	MedDRA (10.0)	Systematic Assessment	Taste complaint	EG0003 events3 affected108 at risk EG00191 events62 affected214 at risk
Headache	Nervous system disorders	MedDRA (10.0)	Systematic Assessment		EG00011 events11 affected108 at risk EG00118 events16 affected214 at risk
Nausea	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG000113 events13 affected108 at risk EG00128 events24 affected214 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0007 events7 affected108 at risk EG00114 events13 affected214 at risk
Vomiting	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment		EG0003 events3 affected108 at risk EG00112 events11 affected214 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment		EG0004 events4 affected108 at risk EG00118 events12 affected214 at risk
Insomnia	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment		EG0006 events6 affected108 at risk EG00115 events14 affected214 at risk
Anxiety	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment		EG0006 events6 affected108 at risk EG0016 events6 affected214 at risk

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Placebo	Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles
BG001	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
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo inhaled twice daily via the eFlow nebulizer for 5 consecutive days within a 28-day treatment cycle for up to 12 cycles			32	108	94	108
EG001	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			72	214	197	214