Study Evaluating the Safety and Efficacy of MN-221 as an Adjunct to Standard Therapy in Subjects Experiencing an Acute Exacerbation of Asthma

NCT00838591 | Completed Phase 2 DMC

• 1 other identifier: MN-221-CL-007
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 15

Brief Summary

The objective of this clinical study is to examine the safety and effectiveness of intravenous MN-221 compared to placebo when administered as an adjunct to standard therapy in subjects experiencing an acute exacerbation of asthma.

Conditions

Asthma

Keywords

MN-221; Asthma; Acute; Exacerbation

Outcome Measures

Primary Outcomes (1)

• The primary efficacy analysis will be based on a change in FEV1, expressed as percent of predicted, at Hour 3 when compared to FEV1, expressed as percent of predicted, at the qualifying/screening timepoint.

  Hour 3

Secondary Outcomes (15)

• Change from baseline FEV1 % of predicted (at time points other than Hour 3)

  Hours 1, 2, 3, and 24

• Change from baseline FEV1 (L)

  Hours 1, 2, 3 and 24

• Change from baseline PEFR (L/sec)

  Hours 1, 2, 3 and 24

• Change from baseline PEFR, expressed as percent (%) of predicted

  Hours 1, 2, 3and 24

• Improvement in Dyspnea index scale

  Hours 1, 2, 3, 24 and Day 8

Study Arms (2)

1

EXPERIMENTAL

MN-221 given i.v. 1-hour infusion a total dose of 1200 μg (40 μg/min for 15 min \[600 μg\] + 13.3 μg/min for 45 min \[600 μg\]) as an adjunct to the standard of care for acute exacerbation of asthma.

Drug: MN-221

Placebo

PLACEBO COMPARATOR

Placebo (Lot #CLO-095) was packaged in identical vials containing only excipients and administered as an i.v. 1-hour infusion with a regimen as described for MN-221.

Drug: Placebo

Interventions

MN-221 DRUG

Dose: intravenous 1-hour infusion of MN-221 (total dose 1200 μg) or matching placebo.

Also known as: bedoradrine sulfate

1

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects meeting all of the following criteria will be considered for admission to the study:
• Male or female 18 to 65 years of age, inclusive;
• Self-reported history of physician-diagnosed and treated asthma for ≥ 3 months prior to randomization;
• A diagnosis of an acute exacerbation of asthma upon presentation at the ED as defined by dyspnea and evidence of bronchospasm;
• Received the following Standardized Treatment within a 2-hour time window and prior to obtaining the Qualifying Spirometry value(FEV1):
• Supplemental oxygen given to maintain oxygen saturation as measured by pulse oximetry of ≥ 90% as needed;
• Albuterol 5-15mg of albuterol via nebulizer prior to the qualifying spirometry evaluation; simultaneously with
• Ipratropium 0.5-1.5 mg of ipratropium via nebulizer prior to the qualifying spirometry evaluation;
• One dose of corticosteroid of at least 50 mg given orally (prednisone) or intravenously (methylprednisolone) or the equivalent dose of another corticosteroid.
• FEV1 of ≤ 50% of predicted; NOTE: Spirometry to measure the subject's FEV1 expressed as % of predicted within 30 minutes of completing administration of 5 mg (but not more than 15 mg) albuterol and 0.5 mg (but not more than 1.5 mg) of ipratropium..
• Negative urine pregnancy test for all females of child-bearing potential;
• ECG with no dysrhythmias (except sinus tachycardia);
• No clinical or electrocardiographic signs of ischemic heart disease as determined by the Investigator; and
• Legally effective written informed consent obtained prior to starting any mandated study procedures

You may not qualify if:

• Subjects will be excluded if they meet any of the following criteria:
• Administration of a parenteral (intravenous or subcutaneous) beta agonist (e. g., albuterol, terbutaline, epinephrine) within 6 hours prior to randomization;
• A current or prior diagnosis or suspected diagnosis of COPD or other chronic lung disease other than asthma;
• Presence of pneumonia;
• Presence of significant other respiratory dysfunction such as pneumothorax, pneumomediastinum, or pulmonary edema;
• Known or suspected vocal cord dysfunction syndrome;
• Presence of aspirated foreign body (known or suspected);
• History or any current clinical evidence suggesting cardiomyopathy or congestive heart failure;
• History or presence of tachyarrhythmias, with the exception of sinus tachycardia;
• Heart rate ≥ 140 bpm;
• Hypokalemia, defined as subjects with serum potassium level of \<2.8 mEq/L (≤2.8 mmol/L) obtained at Screening (local stat lab, blood gas analysis, or other point of care device) with the following exception:
• For the subjects using non-potassium-sparing diuretics (i.e. loop-diuretic or thiazide diuretic) without "potassium-sparing diuretics" (e.g., Triamterene or Spironolactone) OR without potassium supplementation of at least KCl 20 mEq/day whose potassium level \<3.5 mEq/L (\<3.5 mmol/L) at Screening.
• Significant cardiac, renal, hepatic, endocrine, metabolic, neurologic or other systemic disease. A significant disease will be defined as one which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study or the subject's ability to participate in the trial;
• Self-reported history of greater than 20 pack-yr smoking history;
• Fever ≥ 102.0 ºF (38.9 ºC);

Sponsors & Collaborators

• MediciNova: lead

Study Sites (15)

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

UCSD Medical Center - Thornton Hospital

San Diego, California, 92037, United States

Location

UCSD Medical Center

San Diego, California, 92103, United States

Location

Olive View - UCLA Medical Center

Sylmar, California, 91342, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Newton - Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0563, United States

Location

Albert Einstein Healthcare Network

Philadelphia, Pennsylvania, 19141, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Sentara General Hospital

Norfolk, Virginia, 23507, United States

Location

Related Publications (2)

• House SL, Matsuda K, O'Brien G, Makhay M, Iwaki Y, Ferguson I, Lovato LM, Lewis LM. Efficacy of a new intravenous beta2-adrenergic agonist (bedoradrine, MN-221) for patients with an acute exacerbation of asthma. Respir Med. 2015 Oct;109(10):1268-73. doi: 10.1016/j.rmed.2015.08.003. Epub 2015 Aug 14.

  PMID: 26324315 DERIVED

• Schneider JE, Lewis LM, Ferguson I, House SL, Liu J, Matsuda K, Johnson K. Repeated dyspnea score and percent FEV1 are modest predictors of hospitalization/relapse in patients with acute asthma exacerbation. Respir Med. 2014 Sep;108(9):1284-91. doi: 10.1016/j.rmed.2014.06.006. Epub 2014 Jul 8.

  PMID: 25087835 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

bedoradrine

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Kazuko Matsuda, MD

  MediciNova

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2009
• First Posted: February 6, 2009
• Study Start: March 1, 2009
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: September 5, 2013

Record last verified: 2013-09

Locations

US (15)