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

Theron Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: TRN-157; Other: Placebo; Drug: Tiotropium

Study type: Interventional

Funder types: Industry

Identifiers

NCT02382510

TRN-157-102

Details and patient eligibility

About

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

Enrollment: 59 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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59 participants in 3 patient groups, including a placebo group

TRN-157

Experimental group

Treatment:

Drug: TRN-157

Placebo

Placebo Comparator group

Treatment:

Other: Placebo

Tiotropium

Active Comparator group

Treatment:

Drug: Tiotropium