Dose-Finding, Safety, Pharmacodynamic Effect Study of Sodium Nitrite Inhalation Solution in Normal, Healthy Volunteers

Study Overview
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Brief Summary
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This study is designed to investigate the safety and tolerability of AIR001 Inhalation Solution when administered under conditions of hypoxia and to identify dose levels of drug resulting in a reduction in pulmonary arterial pressure under these hypoxic conditions.

Official Title
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A Placebo-Controlled, Phase 1b, Dose-Finding, Safety, Pharmacodynamic Effect Study of Sodium Nitrite Inhalation Solution (AIR001 INHALATION SOLUTION) in Normal, Healthy Volunteers

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Sodium Nitrite Inhalation Solution
* Drug: Placebo and AIR001 Inhalation Solution (Expansion arm)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal male and female volunteers Age 18-55 Demonstrate a rise in pulmonary artery pressure to low inspired oxygen concentration (a normal response to breathing a low level of oxygen) Exclusion Criteria: Significant medical illnesses Risk factors for pulmonary hypertension G6PD or Cytochrome B5 Reductase deficiencies History of any form of altitude sickness Current prescription or over the counter medication use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dose level 1<br>a single dose (5 mg sodium nitrite)of AIR001 Inhalation Solution administered by inhalation following nebulization | Drug: Sodium Nitrite Inhalation Solution<br>* a single dose of AIR001 Inhalation Solution administered by inhalation following nebulization<br>* Other names: AIR001 Inhalation Solution;|
| Active Comparator: Dose level 2<br>a single dose(15 mg sodium nitrite) of AIR001 Inhalation Solution administered by inhalation following nebulization | Drug: Sodium Nitrite Inhalation Solution<br>* a single dose of AIR001 Inhalation Solution administered by inhalation following nebulization<br>* Other names: AIR001 Inhalation Solution;|
| Active Comparator: Dose level 3<br>a single dose(45 mg sodium nitrite) of AIR001 Inhalation Solution administered by inhalation following nebulization | Drug: Sodium Nitrite Inhalation Solution<br>* a single dose of AIR001 Inhalation Solution administered by inhalation following nebulization<br>* Other names: AIR001 Inhalation Solution;|
| Active Comparator: Dose level 4<br>a single dose(113 mg sodium nitrite) of AIR001 Inhalation Solution administered by inhalation following nebulization | Drug: Sodium Nitrite Inhalation Solution<br>* a single dose of AIR001 Inhalation Solution administered by inhalation following nebulization<br>* Other names: AIR001 Inhalation Solution;|
| Placebo Comparator: Expansion arm<br>On Day 1, subjects will receive a single placebo-form dose of inhaled nebulized AIR001 Inhalation Solution (containing diluent and excipient solutions alone). On Day 2, the same subjects will receive a single administration of AIR001 Inhalation Solution at the minimum pharmacologically active and safe dose identified from dose levels 1-4. Subjects will be blinded to the treatment schema. | Drug: Placebo and AIR001 Inhalation Solution (Expansion arm)<br>* On Day 1, subjects will receive a single placebo-form dose of inhaled nebulized AIR001 Inhalation Solution (containing diluent and excipient solutions alone). On Day 2, the same subjects will receive a single administration of AIR001 Inhalation Solution at the minimum pharmacologically active and safe dose identified from dose levels 1-4. Subjects will be blinded to the treatment schema.<br>* Other names: AIR001 Inhalation Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The measurement of pulmonary arterial pressures by echocardiography. |  | Pretreatment and up to 2 hours post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetics |  | Pretreatment to 8 hours post treatment | 
| Hematology, blood chemistry, coagulation and urinalysis, methemoglobin, oxygen saturation, electrocardiogram, troponin, and vital signs and adverse events. |  | Pretreatment, post treatment, and 24 hours post treatment |