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

Phase 2

Completed

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

Recruitment & Eligibility

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- LABA (but may be withdrawn and converted to SABA x 7 days prior to entry)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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
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	After 2 weeks of treatment with TRN-157 vs. Placebo	Adverse events and/or clinically significant changes in vital signs, ECG, and/or laboratory values

Secondary Outcome Measures

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

Locations (6): Sylvana Research
🇺🇸
San Antonio, Texas, United States
WCCT Global
🇺🇸
Costa Mesa, California, United States
Dr. Winder & Associates/Toledo Center for Clinical Research
🇺🇸
Sylvania, Ohio, United States
West Houston Clinical Research Services
🇺🇸
Houston, Texas, United States
The Allergy and Asthma Center of Southern Oregon
🇺🇸
Medford, Oregon, United States
Allied Clinical Research
🇺🇸
Reno, Nevada, United States