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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MediciNova
ClinicalTrials.gov Identifier:
NCT00838591
First received: February 5, 2009
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: MN-221
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: MN-221-CL-007: A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of MN-221 When Administered Intravenously as an Adjunct to Standard Therapy to Adults With an Acute Exacerbation of Asthma

Resource links provided by NLM:


Further study details as provided by MediciNova:

Primary Outcome Measures:
  • 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. [ Time Frame: Hour 3 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline FEV1 % of predicted (at time points other than Hour 3) [ Time Frame: Hours 1, 2, 3, and 24 ] [ Designated as safety issue: No ]
  • Change from baseline FEV1 (L) [ Time Frame: Hours 1, 2, 3 and 24 ] [ Designated as safety issue: No ]
  • Change from baseline PEFR (L/sec) [ Time Frame: Hours 1, 2, 3 and 24 ] [ Designated as safety issue: No ]
  • Change from baseline PEFR, expressed as percent (%) of predicted [ Time Frame: Hours 1, 2, 3and 24 ] [ Designated as safety issue: No ]
  • Improvement in Dyspnea index scale [ Time Frame: Hours 1, 2, 3, 24 and Day 8 ] [ Designated as safety issue: No ]
  • Percent of subjects with an improvement in FEV1 ≥ 200cc [ Time Frame: Hours 1, 2, 3 and 24 ] [ Designated as safety issue: No ]
  • Percent of subjects with an improvement in FEV1, % predicted ≥ 5% [ Time Frame: Hours 1, 2, 3 and 24 ] [ Designated as safety issue: No ]
  • Percent of subjects with and improvement in FEV1, % predicted ≥ 10% [ Time Frame: Hours 1, 2, 3 and 24 ] [ Designated as safety issue: No ]
  • Subjects Hospitalized ( within 24 hour from start of study drug infusion) [ Time Frame: Within 24 hours from start of study drug infusion. ] [ Designated as safety issue: No ]
  • Admitted to ICU (within 24 hours from start of study drug infusion) [ Time Frame: Within 24 hours from start of study drug infusion. ] [ Designated as safety issue: No ]
  • Number of albuterol treatments to achieve an increase in FEV1% of predicted ≥ 15% [ Time Frame: Hours 3 ] [ Designated as safety issue: No ]
  • Total dose or number of albuterol treatments in first 3 hours following commencement of randomized medication. [ Time Frame: No specific time points ] [ Designated as safety issue: No ]
  • Time to achieve an increase of FEV1% of predicted ≥ 15% [ Time Frame: No specific time points ] [ Designated as safety issue: No ]
  • Time to initial albuterol treatment following the commencement of randomized medication [ Time Frame: No specific time points ] [ Designated as safety issue: No ]
  • Hospital length of stay [ Time Frame: No specific timepoints ] [ Designated as safety issue: No ]

Enrollment: 176
Study Start Date: March 2009
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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
Dose: intravenous 1-hour infusion of MN-221 (total dose 1200 μg) or matching placebo.
Other Name: bedoradrine sulfate
Placebo Comparator: Placebo
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

Detailed Description:

This is an international, randomized, double-blind, placebo-controlled, multi-center ED study. Each subject will receive MN-221 or placebo administered through a continuous intravenous infusion in addition to the standardized treatment for an acute exacerbation of asthma.

Upon presentation to the ED for assessment and treatment for an acute exacerbation of asthma the patient should receive standard of care consistent with the international guidelines (e.g., Global Initiative for Asthma [GINA] or the National Asthma Education and Prevention Program [NAEPP]) and required, in part, by this protocol prior to screening procedures being performed.

Prior to any study specific treatment or evaluation being performed a subject must have signed an IRB/EC/REB approved consent form. Once the subject has received the initial treatment regimen the subject will be assessed for response to the treatment including spirometry.If the subject meets all entry criteria the subject will be randomized to receive MN-221 or placebo. Throughout the screening process the subject will continue to receive standardized treatment consistent with the appropriate guidelines for the treatment of acute exacerbations of asthma.

Subjects enrolled in the study will receive an intravenous 1-hour infusion of MN-221 study drug or placebo. Subjects receiving MN-221 will be administered a total dose of 1200 μg.

During the study treatment period, the subject may continue to receive standardized treatment and be assessed. The study treatment period will be approximately 3 hours in length. Safety and efficacy will be monitored throughout the treatment period. PK parameters (if applicable) will be obtained from subjects at selected study sites. A blood sample for genomic evaluation will be collected during the treatment period (at participating sites) if the subject consents to the evaluation. An initial 24-hour post-randomization follow-up visit will be completed to evaluate the subject's health status as well as for safety and PK parameters (if applicable). A second follow-up contact will be completed by telephone seven days post-randomization for safety purposes and to evaluate the subject's health status.

A periodic risk/benefit evaluation will be performed by the study's Data Safety Monitoring Board.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects meeting all of the following criteria will be considered for admission to the study:

    1. Male or female 18 to 65 years of age, inclusive;
    2. Self-reported history of physician-diagnosed and treated asthma for ≥ 3 months prior to randomization;
    3. A diagnosis of an acute exacerbation of asthma upon presentation at the ED as defined by dyspnea and evidence of bronchospasm;
    4. 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.
    5. 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..
    6. Negative urine pregnancy test for all females of child-bearing potential;
    7. ECG with no dysrhythmias (except sinus tachycardia);
    8. No clinical or electrocardiographic signs of ischemic heart disease as determined by the Investigator; and
    9. Legally effective written informed consent obtained prior to starting any mandated study procedures

Exclusion Criteria:

Subjects will be excluded if they meet any of the following criteria:

  1. Administration of a parenteral (intravenous or subcutaneous) beta agonist (e. g., albuterol, terbutaline, epinephrine) within 6 hours prior to randomization;
  2. A current or prior diagnosis or suspected diagnosis of COPD or other chronic lung disease other than asthma;
  3. Presence of pneumonia;
  4. Presence of significant other respiratory dysfunction such as pneumothorax, pneumomediastinum, or pulmonary edema;
  5. Known or suspected vocal cord dysfunction syndrome;
  6. Presence of aspirated foreign body (known or suspected);
  7. History or any current clinical evidence suggesting cardiomyopathy or congestive heart failure;
  8. History or presence of tachyarrhythmias, with the exception of sinus tachycardia;
  9. Heart rate ≥ 140 bpm;
  10. 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.

  11. 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;
  12. Self-reported history of greater than 20 pack-yr smoking history;
  13. Fever ≥ 102.0 ºF (38.9 ºC);
  14. Uncontrolled hypertension defined as a blood pressure ≥ 170/100 mm Hg (22.7/13.3 kPa);
  15. Need for immediate intubation, mechanical ventilation, or non-invasive positive pressure ventilation as determined by the Investigator;
  16. Pregnant or lactating females;
  17. Participated in another clinical study with an investigational drug within 30 days of randomization;
  18. Positive urine drug screen for cocaine, methamphetamine or PCP unless, in the Investigator's clinical judgment, a single positive result is explained by exposure to a non-illicit drug product (i.e., is a false positive). For example, phenylpropanolamine or methylphenidate may read positive in a methamphetamine screen; dextromethorphan in a PCP screen.
  19. Any subject with a known allergy to components of the MN-221 drug product;
  20. Any subject with a known allergy to other beta agonists;
  21. Previous exposure to MN-221; or
  22. Use of theophylline, beta blockers, digoxin, MAO inhibitors, or tricyclic antidepressants within 2 weeks prior to randomization.

Use of non-potassium-sparing diuretics (i.e. Thiazide or Loop-diuretic) without potassium-sparing diuretic OR without potassium supplementation >20 mEq/day within 2 weeks prior to randomization and if serum potassium level at Screening <3.5 mEq/L (<3.5 mmol/L).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00838591

Locations
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
UCSD Medical Center
San Diego, California, United States, 92103
UCSD Medical Center - Thornton Hospital
San Diego, California, United States, 92037
Olive View - UCLA Medical Center
Sylmar, California, United States, 91342
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Massachusetts
Newton - Wellesley Hospital
Newton, Massachusetts, United States, 02462
Baystate Medical Center
Springfield, Massachusetts, United States, 01199
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267-0563
United States, Pennsylvania
Albert Einstein Healthcare Network
Philadelphia, Pennsylvania, United States, 19141
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Virginia
Sentara General Hospital
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
MediciNova
Investigators
Study Director: Kazuko Matsuda, MD MediciNova
  More Information

No publications provided

Responsible Party: MediciNova
ClinicalTrials.gov Identifier: NCT00838591     History of Changes
Other Study ID Numbers: MN-221-CL-007
Study First Received: February 5, 2009
Last Updated: September 4, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
New Zealand: Medsafe
Australia: Human Research Ethics Committee

Keywords provided by MediciNova:
MN-221
Asthma
Acute
Exacerbation

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 23, 2014