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