Multiple Ascending Dose Study of TRN-157 in Stable Mild and Moderate Asthmatics

Study Overview
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Brief Summary
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This multiple ascending dose study is to determine the safety and bronchodilator activity of TRN-157 in 59 mild and moderate asthmatics.

Official Title
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A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose, Two-Way Cross-Over, Phase 2a Study to Evaluate the Safety and Bronchodilator Activity of TRN-157 in Stable Mild and Moderate Asthmatics

Conditions
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Asthma

Intervention / Treatment
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* Drug: TRN-157
* Other: Placebo
* Drug: Tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet the following criteria will be considered eligible to participate in the study: The patient is ≥ 18 and < 70 years of age, and gives informed consent Clinical diagnosis of mild to moderate asthma of at least 6 months duration and age of onset < 50 years Presently using ICS at moderate doses (equivalent to 200-800 µg of budesonide or 88-500 µg of fluticasone daily) ≥ 12% and ≥ 200 mL improvement in FEV1 to 4 puffs albuterol by metered-dose inhaler (MDI) at screening visit Patient is willing to use acceptable form of birth control during trial and for one month thereafter Ability to measure morning (AM) peak expiratory flow (PEF) on schedule using electronic peak flow meter (EPFM) and to complete the study diary correctly at least 70% of the time during the run-in period After 7 day withdrawal from LABA therapy and overnight withdrawal from SABA therapy (except rescue medication), patient has between 55% - 80% of predicted FEV1 at CV2 Exclusion Criteria: A patient meeting any of the following criteria is not eligible for enrollment in the study: A clinical diagnosis of chronic obstructive pulmonary disease (COPD), chronic bronchitis, bronchiectasis, or other significant pulmonary disease other than asthma History of upper or lower respiratory infection within 4 weeks of screening History of asthma exacerbation requiring oral or systemic corticosteroids or hospital admission within 6 months of screening History of myocardial infarction, or cardiac conduction abnormalities, including but not limited to atrial fibrillation, and paroxysmal atrial tachycardia Hospitalization due to cardiac failure within the last 6 months History of narrow angle glaucoma or obstructive uropathy Current smokers or vapers, or former smokers with > 10 pack-year (self-reported) history of smoking Patients who presently use the following medications will not be eligible for participation: Long-acting muscarinic receptor antagonist (LAMA) LABA (but may be withdrawn and converted to SABA x 7 days prior to entry) Leukotriene pathway blockers Anti-IgE antibody (Xolair) within last 6 months prior to CV1 Phosphodiesterase 4 (PDE4) inhibitors (e.g., Roflumilast) Cromolyn Methylxanthines (e.g., aminophylline and theophylline) 5-Lipoxygenase inhibitor (e.g., Zileuton) Allergies to LAMA therapies History of life-threatening asthma exacerbation requiring ICU admission, mechanical ventilation, or tracheostomy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRN-157<br> | Drug: TRN-157<br> <br> |
| Placebo Comparator: Placebo<br> | Other: Placebo<br> <br> |
| Active Comparator: Tiotropium<br> | Drug: Tiotropium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in FEV1 |  | After 2 weeks of treatment with TRN-157 vs. Placebo | 
| Safety and tolerability as determined by number of subjects with adverse events | Adverse events and/or clinically significant changes in vital signs, ECG, and/or laboratory values | After 2 weeks of treatment with TRN-157 vs. Placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize effects on pulmonary function | FEV1(0-4 h); FVC AUC(0-4 h); FVC(0-4 h); Morning PEFR; Trough (pre-dose) FEV1 | After 2 weeks of treatment with TRN-157 vs. Placebo | 
| Characterize effects on asthma symptomatology | Asthma symptoms, including exacerbations; Number of asthma-control days; Rescue inhaler use; Nocturnal symptoms | During the 2 weeks of treatment with TRN-157 vs. Placebo | 
| Determination of pharmacokinetic parameters: AUC0-t, AUC0-inf, Cmax, tmax, t½, elimination rate constant (kel), volume of distribution at steady state (Vss/F), total plasma clearance (CL/F) | AUC0-t, AUC0-inf, Cmax, tmax, t½, elimination rate constant (kel), volume of distribution at steady state (Vss/F), total plasma clearance (CL/F) | After 2 weeks of treatment with TRN-157 |