Study Evaluating the Safety and Effects of MN-221 in Subjects Experiencing an Acute Exacerbation of Asthma - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Single Blind (Subject); Primary Purpose: Treatment
Conditions:	Asthma Status Asthmaticus
Interventions:	Drug: Dose Group 1 Drug: MN-221 placebo Drug: Dose Group 2 Drug: Dose Group 3

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Upon presentation to the Emergency Department (ED) at a hospital participating in the study with an acute exacerbation of asthma, the Principal Investigator (ED physician) discussed the study with the potential subject.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Some subjects were consented for the study, but upon screening, failed to meet the inclusion and exclusion criteria, had an FEV1 > 50%, or refused to participate.

Reporting Groups

	Description
240 μg MN-221 i.v. (Intravenous) Infusion for 15 Minutes	Initial dose: 16 μg/min of MN-221 for 15 minutes (total 240 μg). After safety data review meeting, chose escalation doses: 1) 30 μg/min for 15 minutes (total 450 μg), and 2) 16 μg/min for 15 minutes plus 8 μg/min for 105 minutes (total dose of 1,080 μg).Until the subject’s FEV1 reached ≥ 70% predicted, the subject continued to receive the following standard treatment and assessment during the study treatment period: Assessment of subject’s signs and symptoms Completion of a dyspnea index scale Supplemental oxygen to maintain oxygen saturation, as measured by pulse oximetry of ≥ 90% Albuterol (2.5 mg) via nebulizer given hourly NOTE: Albuterol (2.5 mg) via nebulizer and/or Ipratropium (0.5 mg) via nebulizer may have been given up to every 20 minutes and every hour, respectively, if deemed to be indicated by the Investigator. Spirometry completed within 10 minutes of nebulizer treatments, followed by Reassessment of signs and symptoms. If the subj
MN-221 Placebo i.v. Infusion	MN-221 Placebo i.v. infusion. Until the subject’s FEV1 reached ≥ 70% predicted, the subject continued to receive the following standard treatment and assessment during the study treatment period: Assessment of subject’s signs and symptoms,Completion of a dyspnea index scale,Supplemental oxygen to maintain oxygen saturation, as measured by pulse oximetry of ≥ 90%,Albuterol (2.5 mg) via nebulizer given hourly. NOTE: Albuterol (2.5 mg) via nebulizer may have been given up to every 20 minutes if deemed to be indicated by the Investigator. Ipratropium (0.5 mg) via nebulizer may have been given every hour if deemed to be indicated by the Investigator. Spirometry completed within 10 minutes of nebulizer treatments, followed by Reassessment of signs and symptoms. If the subject did not improve to FEV1 ≥70% of predicted during the study treatment period, the subject may have continued to receive further treatment, including hospital admission, at the discretion of the Investigator.
1,000-1,080 μg MN-221 i.v.	16 μg/minute for 15 minutes followed by 8 μg/minute for 105 minutes (total dose of 1,080 μg). Among the subjects in the 1,000 - 1,080 μg group, per protocol instructions, the two subjects originally randomized to receive 1,080 μg MN-221 were infused with study drug over a 120-minute period and the 1 subject originally randomized to receive 450 μg who actually received 1,000 μg was infused with study drug over a 15-minute period. Although there was this difference in infusion time, it was deemed appropriate to group these 3 subjects in the same dose group.
450 μg MN-221 i.v. for 15 Minutes	30 μg/minute for 15 minutes (total dose of 450 μg) administered i.v.
1,995 μg MN-221 i.v. Over 15 Minutes and 25 Minutes	Two subjects were randomized to receive 450 μg dose i.v. Instead, Subject 0010015 received 1,995 μg i.v. over 15 minutes infusion; Subject 0010016 received 1,995 μg i.v. over 25 minutes infusion.

Participant Flow: Overall Study

	240 μg MN-221 i.v. (Intravenous) Infusion for 15 Minutes	MN-221 Placebo i.v. Infusion	1,000-1,080 μg MN-221 i.v.	450 μg MN-221 i.v. for 15 Minutes	1,995 μg MN-221 i.v. Over 15 Minutes and 25 Minutes
STARTED	5	13	3	6	2
COMPLETED	5	12	3	6	2
NOT COMPLETED	0	1	0	0	0
Lost to Follow-up	0	1	0	0	0

Baseline Characteristics

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Reporting Groups

	Description
240 μg MN-221 i.v. (Intravenous) Infusion for 15 Minutes	Initial dose: 16 μg/min of MN-221 for 15 minutes (total 240 μg). After safety data review meeting, chose escalation doses: 1) 30 μg/min for 15 minutes (total 450 μg), and 2) 16 μg/min for 15 minutes plus 8 μg/min for 105 minutes (total dose of 1,080 μg).Until the subject’s FEV1 reached ≥ 70% predicted, the subject continued to receive the following standard treatment and assessment during the study treatment period: Assessment of subject’s signs and symptoms Completion of a dyspnea index scale Supplemental oxygen to maintain oxygen saturation, as measured by pulse oximetry of ≥ 90% Albuterol (2.5 mg) via nebulizer given hourly NOTE: Albuterol (2.5 mg) via nebulizer and/or Ipratropium (0.5 mg) via nebulizer may have been given up to every 20 minutes and every hour, respectively, if deemed to be indicated by the Investigator. Spirometry completed within 10 minutes of nebulizer treatments, followed by Reassessment of signs and symptoms. If the subj
MN-221 Placebo i.v. Infusion	MN-221 Placebo i.v. infusion. Until the subject’s FEV1 reached ≥ 70% predicted, the subject continued to receive the following standard treatment and assessment during the study treatment period: Assessment of subject’s signs and symptoms,Completion of a dyspnea index scale,Supplemental oxygen to maintain oxygen saturation, as measured by pulse oximetry of ≥ 90%,Albuterol (2.5 mg) via nebulizer given hourly. NOTE: Albuterol (2.5 mg) via nebulizer may have been given up to every 20 minutes if deemed to be indicated by the Investigator. Ipratropium (0.5 mg) via nebulizer may have been given every hour if deemed to be indicated by the Investigator. Spirometry completed within 10 minutes of nebulizer treatments, followed by Reassessment of signs and symptoms. If the subject did not improve to FEV1 ≥70% of predicted during the study treatment period, the subject may have continued to receive further treatment, including hospital admission, at the discretion of the Investigator.
1,000-1,080 μg MN-221 i.v.	16 μg/minute for 15 minutes followed by 8 μg/minute for 105 minutes (total dose of 1,080 μg). Among the subjects in the 1,000 - 1,080 μg group, per protocol instructions, the two subjects originally randomized to receive 1,080 μg MN-221 were infused with study drug over a 120-minute period and the 1 subject originally randomized to receive 450 μg who actually received 1,000 μg was infused with study drug over a 15-minute period. Although there was this difference in infusion time, it was deemed appropriate to group these 3 subjects in the same dose group.
450 μg MN-221 i.v. for 15 Minutes	30 μg/minute for 15 minutes (total dose of 450 μg) administered i.v.
1,995 μg MN-221 i.v. Over 15 Minutes and 25 Minutes	Two subjects were randomized to receive 450 μg dose i.v. Instead, Subject 0010015 received 1,995 μg i.v. over 15 minutes infusion; Subject 0010016 received 1,995 μg i.v. over 25 minutes infusion.

Baseline Measures

	240 μg MN-221 i.v. (Intravenous) Infusion for 15 Minutes	MN-221 Placebo i.v. Infusion	1,000-1,080 μg MN-221 i.v.	450 μg MN-221 i.v. for 15 Minutes	1,995 μg MN-221 i.v. Over 15 Minutes and 25 Minutes	Total
Number of Participants [units: participants]	5	13	3	6	2	29
Age [units: participants]
<=18 years	0	0	0	0	0	0
Between 18 and 65 years	5	13	3	6	2	29
>=65 years	0	0	0	0	0	0
Age [units: years] Mean ± Standard Deviation	30.2 ± 11.56	42.6 ± 9.7	22.3 ± 3.21	39.2 ± 9.77	45 ± 0.0	37.83 ± 11.31
Gender [units: participants]
Female	3	7	3	6	2	21
Male	2	6	0	0	0	8
Region of Enrollment [units: participants]
United States	5	13	3	6	2	29

Outcome Measures

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1. Primary:

Change of FEV1 (Forced Expiratory Volume in 1 Second) Expressed as Percent of Predicted After Two Doses of Albuterol (5 mg Each) and Ipratropium (0.5 mg Each) When Compared to FEV1 at Hour 2 After the Start of the Infusion of MN-221 or Placebo. [ Time Frame: Baseline and Hour 2 ]

Show Outcome Measure 1

2. Secondary:

FEV1 (L) The Forced Expiratory Volume in One Second as Measured in Liters Per Second. [ Time Frame: Baseline to Hour 2 ]

Show Outcome Measure 2

3. Secondary:

Hospital Admission Rate During Visit 1 [ Time Frame: Hour -1.5 through Hour 5 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Kazuko Matsuda, MD PhD MPH, Vice President, Clinical Development
Organization: MediciNova, Inc.
phone: 858-373-1500 ext 132
e-mail: matsuda@medicinova.com

No publications provided

Responsible Party:	MediciNova
ClinicalTrials.gov Identifier:	NCT00683449 History of Changes
Other Study ID Numbers:	MN-221-CL-006
Study First Received:	May 21, 2008
Results First Received:	February 16, 2011
Last Updated:	October 5, 2011
Health Authority:	United States: Food and Drug Administration