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

Sponsor:	MediciNova
Information provided by (Responsible Party):	MediciNova
ClinicalTrials.gov Identifier:	NCT00838591

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	Phase II

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:

MedlinePlus related topics: Asthma

Drug Information available for: Albuterol Ipratropium bromide Ipratropium Bedoradrine sulfate

U.S. FDA Resources

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 ]

Estimated Enrollment:	200
Study Start Date:	March 2009
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	September 2011 (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]).	Drug: MN-221 Dose: intravenous 1-hour infusion of MN-221 (total dose 1200 μg) or MN-221 Placebo. Other Names: Albuterol Ipratropium
Placebo Comparator: 2 MN-221 Placebo: Subjects enrolled in the study will receive an intravenous 1-hour infusion of MN-221 placebo	Drug: MN-221 Dose: intravenous 1-hour infusion of MN-221 (total dose 1200 μg) or MN-221 Placebo. Other Names: Albuterol Ipratropium

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:

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);
Uncontrolled hypertension defined as a blood pressure ≥ 170/100 mm Hg (22.7/13.3 kPa);
Need for immediate intubation, mechanical ventilation, or non-invasive positive pressure ventilation as determined by the Investigator;
Pregnant or lactating females;
Participated in another clinical study with an investigational drug within 30 days of randomization;
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.
Any subject with a known allergy to components of the MN-221 drug product;
Any subject with a known allergy to other beta agonists;
Previous exposure to MN-221; or
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

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

Contacts

Contact: Regan Burns, B.A.

858-373-1500 ext 121

burns@medicinova.com

Locations

United States, California
Loma Linda University Medical Center	Not yet recruiting
Loma Linda, California, United States, 92354
Contact: Ellen Reibling 909-558-7407 ereibling@llu.edu
Principal Investigator: Elizabeth Walters, MD
UCSD Medical Center	Recruiting
San Diego, California, United States, 92103
Contact: Jean Marshall, RN 619-543-6554 jbmarshall@ucsd.edu
Principal Investigator: David Guss, MD
UCSD Medical Center - Thornton Hospital	Recruiting
San Diego, California, United States, 92037
Contact: Kevin Fulton 858-657-7660 kfulton@ucsd.edu
Principal Investigator: David Guss, MD
Olive View - UCLA Medical Center	Recruiting
Sylmar, California, United States, 91342
Contact: Kavitha Pathmarajah 818-364-3115 kpathmar@gmail.com
Principal Investigator: Luis Lovato, MD
United States, Illinois
Loyola University Medical Center	Recruiting
Maywood, Illinois, United States, 60153
Contact: Christine Stake 708-327-2559 cstake@lumc.edu
Principal Investigator: Beatrice D. Probst, MD
United States, Massachusetts
Newton - Wellesley Hospital	Recruiting
Newton, Massachusetts, United States, 02462
Contact: Kara Malcolm, RN, CCRC 617-243-5089 kmalcolm@partners.org
Principal Investigator: David Huckins, MD
Baystate Medical Center	Recruiting
Springfield, Massachusetts, United States, 01199
Contact: Del Blank, RN 413-794-8680 fidela.blank@baystatehealth.org
Principal Investigator: Howard Smithline, MD
United States, Minnesota
Hennepin County Medical Center	Recruiting
Minneapolis, Minnesota, United States, 55415
Contact: Daniel Joyce 612-873-9528 daniel.ddj207@gmail.com
Contact: Rebecca Nelson 612-873-9528 rsnelson08@gmail.com
Principal Investigator: Richard O. Gray, MD
United States, Missouri
Washington University School of Medicine	Recruiting
St. Louis, Missouri, United States, 63110
Contact: Kristen Aubuchon 314-362-8041 aubuchonk@wusm.wustl.edu
Principal Investigator: Lawrence Lewis, MD
United States, New Jersey
Hackensack University Medical Center	Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Barbara McGoey, RN 201-996-5458 Bmcgoey@humed.com
Principal Investigator: Chinwe Ogedegbe, MD
United States, Ohio
University of Cincinnati	Recruiting
Cincinnati, Ohio, United States, 45267-0563
Contact: Jillian Picard, RN 513-558-0924 Jillian.picard@uc.edu
Principal Investigator: Jonathan Bernstein, MD
United States, Pennsylvania
Albert Einstein Healthcare Network	Recruiting
Philadelphia, Pennsylvania, United States, 19141
Contact: Kathia Damiron, MD 215-456-7579 damironk@Einstein.edu
Principal Investigator: John J Kelly, MD
United States, Rhode Island
Rhode Island Hospital	Recruiting
Providence, Rhode Island, United States, 02903
Contact: Karina Bertsch 401-444-6656 kbertsch@lifespan.org
Principal Investigator: Gregory Jay, MD
United States, Texas
University of Texas Southwestern Medical Center	Recruiting
Dallas, Texas, United States, 75390
Contact: Ariza Sisavath 214-648-2767 ariza.sisavath@utsouthwestern.edu
Principal Investigator: Ava Pierce, MD
United States, Virginia
Sentara General Hospital	Recruiting
Norfolk, Virginia, United States, 23507
Contact: LaBarbara Edlow, RN 757-388-5224 ldedlow@sentara.com
Principal Investigator: Frank Counselman, MD

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 7, 2011
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
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Ipratropium
Bronchodilator Agents

Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012