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

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

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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: Placebo; Drug: TRN-157; Drug: Tiotropium

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, United States
      • WCCT Global
    • Gold River, California, United States, 95670
      • Allied Clinical Research
  • Nevada
    • Reno, Nevada, United States, 89503
      • Allied Clinical Research
  • Ohio
    • Sylvania, Ohio, United States
      • Dr. Winder & Associates/Toledo Center for Clinical Research
  • Oregon
    • Medford, Oregon, United States
      • The Allergy and Asthma Center of Southern Oregon
  • Texas
    • Houston, Texas, United States
      • West Houston Clinical Research Services
    • San Antonio, Texas, United States
      • Sylvana Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Theron Pharmaceuticals, Inc.
• Investigators: Study Director: Kenneth Krantz, MD, PhD, Theron Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: February 17, 2015
• First Submitted That Met QC Criteria: March 5, 2015
• First Posted (Estimate): March 6, 2015

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide
• Other Study ID Numbers: TRN-157-102