Clinical trial NCT00683449
Conditions: Asthma Status Asthmaticus
Keywords: Asthma Dose-Escalation Controlled MN-221
Sponsor: MediciNova
Start date: 2008-06-01; Completion date: 2009-03-01
Enrollment: 29 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Detailed description:
This is a randomized, modified single-blind, placebo-controlled dose escalation, multi-center Emergency Department (ED) study. Each subject will receive MN-221 or placebo administered through a continuous intravenous infusion in addition to the standardized care treatment for an acute exacerbation of asthma. The study is a modified single-blind design where the subject and the Investigator will be blinded.

Upon presentation to the ED for assessment and treatment for an acute exacerbation of asthma the subject should receive standardized care consistent with the National Asthma Education and Prevention Program (NAEPP) guidelines.

Once the subject has received the standardized initial treatment regimen and has been assessed for response to that treatment (signs and symptoms of acute asthma exacerbation), an informed consent to participate in the study will be obtained, study entry criteria will be reviewed, a 12-lead ECG will be performed, a dyspnea index scale assessment will be conducted, and spirometry will be performed. If the subject's FEV1 is ≤ 55% of predicted and the subject meets all other study entry criteria the subject will be randomized to receive either MN-221 or placebo. Throughout the screening process the subject will continue to receive the appropriate medical care consistent with the NAEPP guidelines for the treatment of acute exacerbations of asthma.

There will be up to three dose groups with generally twelve subjects in each group. Subjects enrolled in the study will receive an intravenous infusion of MN-221 study drug or placebo. Generally six subjects will be randomized to receive MN-221 and generally six subjects will be randomized to receive placebo in each dose group.

The initial dose group will be randomized to receive:

* 16 μg/min of MN-221 for 15 minutes (total dose of 240 μg) or placebo.

Subsequent dose groups will receive the following proposed doses:

* 30 μg/min for 15 minutes (total dose of 450 μg) or placebo, and
* 16 μg/min for 15 minutes followed by 8 μg/min for 105 minutes (total dose of 1,080 μg) or placebo.

During the study treatment period, the subject will continue to receive the following standard treatment and assessment until the subject's FEV1 reaches ≥ 70% of predicted:

* Assessment of subject's signs and symptoms;
* Complete 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 be given up to every 20 minutes if deemed to be indicated by the Investigator.
* Ipratropium (0.5 mg) via nebulizer may be 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 does not improve to FEV1 ≥ 70% of predicted during the study treatment period, the subject may continue to receive further treatment including hospital admission at the discretion of the Investigator. The study will be approximately 6.5 hours in length (Hour -1.5 to Hour 5) while the subject remains in the ED. Safety, efficacy and PK parameters will be monitored throughout the treatment period. 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. 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 risk/benefit evaluation will be performed by the study's Safety Review Committee at each dose level. The occurrence of clinical signs, symptoms, laboratory abnormalities, ECG abnormalities suggesting toxicity, or results of efficacy analyses (FEV1, dyspnea index scale), may result in a decision to modify the proposed planned dose escalations, to repeat a dose level, or to not evaluate any additional dose(s) of MN-221.

Arms: arm 1: MN-221 total dose of 240 mcg arm 2: i.v. infusion of MN-221 Placebo for 15 min
Interventions: intervention 1: Dose Group 1 intervention 2: MN-221 placebo intervention 3: Dose Group 2 intervention 4: Dose Group 3
Intervention descriptions: intervention 1: IV infusion of MN-221 16 mcg/min for 15 min; total dose of 240 mcg intervention 2: i.v. infusion of placebo for 15 minutes intervention 3: i.v. infusion of MN-221 30 mcg/min for 15 minutes (total dose of 450 mcg) intervention 4: i.v. infusion of MN-221 16 mcg/min for 15 minutes followed by 8 mcg/min for 105 minutes (total dose = 1,080 mcg)

Protocol documents: