Asthma
Conditions
Brief summary
This multiple ascending dose study is to determine the safety and bronchodilator activity of TRN-157 in 59 mild and moderate asthmatics.
Interventions
Sponsors
Theron Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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will not be eligible for participation: * Long-acting muscarinic receptor antagonist (LAMA) * LABA (but may be withdrawn and converted to SABA x 7 days prior to entry) * Leukotriene pathway blockers * Anti-IgE antibody (Xolair) within last 6 months prior to CV1 *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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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) |
Countries
United States
Outcome results
None listed