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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02382510
• Other study ID #: TRN-157-102
• Status: Completed
• Phase: Phase 2
• First received: February 17, 2015
• Last updated: May 8, 2017
• Start date: April 2015
• Est. completion date: March 2016

Study information

• Verified date: May 2017
• Source: Theron Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• TRN-157

Other:
• Placebo

Drug:
• Tiotropium

Locations

Country	Name	City	State
United States	WCCT Global	Costa Mesa	California
United States	Allied Clinical Research	Gold River	California
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	Sylvana Research	San Antonio	Texas
United States	Dr. Winder & Associates/Toledo Center for Clinical Research	Sylvania	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Theron Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in FEV1		After 2 weeks of treatment with TRN-157 vs. Placebo
Primary	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	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
Secondary	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
Secondary	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