Single Ascending Dose Study of TRN-157 in Healthy Subjects

Study Overview
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Brief Summary
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This single ascending dose study is to determine and evaluate the safety and tolerability of TRN-157 in approximately 40 healthy subjects.

Official Title
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A Phase I, Randomized, Double-blind, Placebo Controlled, Single Ascending Dose Study to Evaluate the Safety and Tolerability of Nebulized, TRN-157 Inhalation Solution in Healthy Subjects

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: TRN-157
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided written informed consent The subject is male or female 18 to 65 years of age If the subject or subject's partner is of childbearing potential, a medically acceptable form of contraception will be Non-smoker Good general health Willing to abstain from alcohol, caffeine, and xanthine-containing beverages The subject is compliant and available throughout the entire study period Exclusion Criteria: Current diagnosis, as per subject or investigator or screening assessment, of: unstable or uncontrolled disease in any organ system (including cardiovascular) on present therapy history of narrow angle glaucoma history of alcohol abuse within the past 5 years history of smoking within the past 6 months positive result for the alcohol and/or drugs of abuse weight > 100 kg or < 50 kg clinically significant abnormal ECG history of clinically significant (per the Investigator) disease or disorder any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results Abnormal vital signs defined as any of the following: Systolic blood pressure ≥ 140 mmHg Diastolic blood pressure ≥ 90mmHg Heart rate < 40 or > 85 beats per minute Fever or other clinically significant physical exam findings Current or history of clinically significant respiratory disease, including asthma, emphysema, chronic bronchitis, or cystic fibrosis History or current symptom(s) of respiratory tract inflammation Inability to perform reproducible spirometry in accordance with American Thoracic Society (ATS) guidelines Abnormal FEV1, FVC, or FEV1/FVC (FEV1 or FVC < 80% of predicted or FEV1/FVC ratio < 0.7) FEV1 variability > 10% between study visits Female of childbearing potential with a positive serum pregnancy test or currently breastfeeding Currently being treated for hypertension or taking any other medications that affect blood pressure significantly Inability to perform acceptable, quality serial spirometry or any other study procedures Positive screen for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, or HIV antibody

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRN-157<br> | Drug: TRN-157<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as determined by number of subjects with adverse events |  | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of pharmacokinetic parameters | Area Under the Plasma Concentration-Time Curve from Zero to the Time of the Last Measurable Concentration (AUC0-t) | 1 week | 
| Determination of pharmacokinetic parameters | Area Under the Plasma Concentration-Time Curve from Zero to Infinity (AUC0-inf) | 1 week | 
| Determination of pharmacokinetic parameters | Peak Plasma Concentration (Cmax) | 1 week | 
| Determination of pharmacokinetic parameters | Time to Peak Plasma Concentration (tmax) | 1 week | 
| Determination of pharmacokinetic parameters | Half-Life (t½) | 1 week | 
| Determination of pharmacokinetic parameters | Elimination Rate Constant (kel) | 1 week | 
| Determination of pharmacokinetic parameters | Volume of Distribution at Steady State after Non-IV Administration (Vss/F) | 1 week | 
| Determination of pharmacokinetic parameters | Total Plasma Clearance after Non-IV Administration (CL/F) | 1 week |