Conditions: Asthma
Keywords: asthma randomized placebo controlled dose escalation safety efficacy single blind MN-221
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 17
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety and tolerability of MN-221 at two different dosing rates administered through a continuous infusion in subjects diagnosed with moderate to severe asthma.

Detailed description:
This is a multi-center, randomized, single-blind\*, parallel group, placebo-controlled, study with two dosing regimens in subjects diagnosed with moderate to severe asthma using MN-221 or placebo. Subjects will be randomized to receive MN-221 or placebo in a 3:1 ratio, MN-221:placebo. Subjects randomized to receive MN-221 will be dosed with active study drug at both dosing visits, and subjects randomized to the placebo arm will receive placebo at both dosing visits. Approximately 25 subjects diagnosed with moderate to severe asthma who have not received inhaled corticosteroid therapy within one month of Screen Visit 1 will be enrolled and will participate throughout the study.

Initial dose:

* 16 μg/min for 15 minutes followed by 8 μg/min for 105 minutes (2-hour infusion with a total dose of 1,080 μg MN-221 or Placebo)

Subsequent dose:

* 30 μg/min for 15 minutes followed by 15 μg/min for 45 minutes (1-hr infusion with a total dose of 1,125 μg MN-221 or Placebo)

There will be approximately a two to four week period between each dose regimen, during which time a safety review will be performed before proceeding to the next dose level. Subjects will be screened for eligibility and continued eligibility will be determined for each subject prior to administering each dose. After the initiation of the intravenous infusion of MN-221 or placebo, serial spirometry will be measured for approximately 24 hours.

For each dose evaluation period, subjects will be domiciled in the clinical research unit (CRU) for 2 nights, beginning on Day -1, one day before dosing. Determination of continued study eligibility will be made on Day -1 for each dose level. Day 1 will include study drug infusion and approximately a 24-hour observation period into Day 2 to allow safety monitoring, serial spirometry, and serum PK measurements. Subjects will be discharged from the CRU on Day 2. They will return to the CRU approximately 2-4 weeks later to participate in the subsequent dose group.

\*This is a "modified" single-blind study in which the subject and Investigator are both blinded regarding the treatment arm.

Arms:
arm 1: None arm 2: Placebo intravenous infusion with dosing volume equivalent to active treatment.

Interventions: intervention 1: MN-221 intervention 2: MN-221 intervention 3: Placebo
Intervention descriptions: intervention 1: Initial dose: 16 μg/min for 15 minutes followed by 8 μg/min for 105 minutes (2-hour infusion with a total dose of 1,080 μg) intervention 2: Subsequent dose: 30 μg/min for 15 minutes followed by 15 μg/min for 45 minutes (1-hr infusion with a total dose of 1,125 μg). intervention 3: Placebo intravenous infusion with dosing volume equivalent to active treatment.

Protocol document: