Clinical trial NCT02382510: Multiple Ascending Dose Study of TRN-157 in Stable Mild and Moderate Asthmatics
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Theron Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-03-06
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in FEV1
timeFrame: After 2 weeks of treatment with TRN-157 vs. Placebo
measure: Safety and tolerability as determined by number of subjects with adverse events
timeFrame: After 2 weeks of treatment with TRN-157 vs. Placebo
Secondary outcomes:
measure: Characterize effects on pulmonary function
timeFrame: After 2 weeks of treatment with TRN-157 vs. Placebo
measure: Characterize effects on asthma symptomatology
timeFrame: During the 2 weeks of treatment with TRN-157 vs. Placebo
measure: 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)
timeFrame: After 2 weeks of treatment with TRN-157
Other outcomes:
Locations:
city: Costa Mesa
country: United States
facility: WCCT Global
state: California
city: Gold River
country: United States
facility: Allied Clinical Research
state: California
city: Reno
country: United States
facility: Allied Clinical Research
state: Nevada
city: Sylvania
country: United States
facility: Dr. Winder & Associates/Toledo Center for Clinical Research
state: Ohio
city: Medford
country: United States
facility: The Allergy and Asthma Center of Southern Oregon
state: Oregon
city: Houston
country: United States
facility: West Houston Clinical Research Services
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research
state: Texas
Study officials:
affiliation: Theron Pharmaceuticals, Inc.
name: Kenneth Krantz, MD, PhD
role: STUDY_DIRECTOR
References: