Cross-Over Study of Subcutaneous Study Drug for the Treatment of Patients With Mild to Moderate Asthma

Study Overview
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Brief Summary
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The objective of this study is to evaluate if single subcutaneous (SC) doses of PL-3994, administered to patients with asthma can achieve a clinically meaningful increase in pulmonary function (Forced Expiratory Volume in one second: FEV1) while maintaining an acceptable safety profile. The study will characterize the bronchodilator effect, dose and safety of PL-3994 in a population of moderately severe, stable asthmatics following overnight withdrawal of beta-2 agonists.

Official Title
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A Phase 2a, Double-Blinded, Multi-Center, Escalating Dose Group, Placebo Controlled, Cross-Over Study to Evaluate the Safety, Efficacy and Tolerability of Subcutaneously Administered PL-3994 for the Treatment of Patients With Mild to Moderate Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: PL-3994


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 Patient has a clinical history of asthma as defined by the National Asthma Education and Prevention Program. Documented bronchodilator response to albuterol as defined by the American Thoracic Society (> 200 mL and > 12% increase in FEV1 after bronchodilator inhalation) FEV1 post-bronchodilator of between 55% and 80% predicted. Currently taking 200-1000 mcg (fluticasone equivalent) of inhaled corticosteroids All inclusion criteria met within the past 12 months. If the subject or subject's partner is of child-bearing potential, a medically acceptable form of contraception will be used for three months prior to the screening visit (females only), for the duration of the study and for one month following the last dose of the study drug. Medically acceptable contraceptives include: (1) surgical sterilization, (2) FDA-approved female hormonal contraceptives, (3) an intrauterine device (IUD), (4) condoms with spermicide, or (5) diaphragm with spermicide. If the subject had a vasectomy greater than 6 months prior to the screen visit, this will also be acceptable. 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 psychiatric disease requiring daily medication, including controlled or uncontrolled schizophrenia or any other uncontrolled psychiatric condition significant neurological disease current or history of any cancer (except non-melanomatous skin cancer) diagnosed less than 5 years prior to screening acute or chronic disease requiring frequent changes in medications or changes in dosages of chronic therapy history of alcohol abuse within the past 5 years positive result for the alcohol and/or drug tests at screening or check-in positive for HIV, or Hep B&C at screening blood donation within 30 days of screening or plasma donation within 7 days of screening weight > 100 kg or < 50 kg clinically significant electrocardiogram (ECG) at screening any clinically significant (per the investigator) lab abnormalities any fever or other clinically significant physical exam abnormalities History of COPD or any other lung disease Greater than 10 packs per year smoking history and any cigarette smoking within the past 12 months Patients unable to withhold bronchodilator treatment for 12 hours prior to dosing Patients with hypoxia at screen or Check -in Visit 2, Day 1 or Visit 3, Day 7 (oxygen saturation measured by pulse oximetry [SpO2] < 90%) Tachycardia (heart rate > 100 beats/min) at screening Currently being treated for Hypertension or taking any other medications that affect blood pressure significantly. Currently taking any medications that inhibit PDE activity or which affect the cyclic guanisine mono-phosphate (cGMP) pathway (e.g. theophylline). These medications will be prohibited during the study and for at least 5 half- lives prior to Check-in Visit 2, Day 1 or Visit 3, Day 7 so that cGMP measurements will not be affected. Hypotension (systolic blood pressure < 110 mmHg) at Screening or Check-in Visit 2, Day 1 or Visit 3, Day 7 Chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <50 mL/m2. Diagnosis of heart failure or history of hospitalization for congestive heart failure. History of coronary artery disease defined as prior myocardial infarction, prior revascularization procedure, or >50% coronary artery obstruction by angiography. Prior history of stroke or transient ischemic attack. Female patients of childbearing potential who are nursing or have a positive pregnancy test at Screening or Check -in Visit 2, Day 1 or Visit 3, Day 7 Any major disability or disease with expected survival less than 6 months Administration of any investigational drug or implantation of investigational device, or participation in another trial, within 30 days of screening. Inability to perform acceptable, quality serial spirometry

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PL-3994 (4 escalating doses)<br> | Drug: PL-3994<br>* subcutaneous PL-3994, single dose, 4 escalating dose groups<br>|
| Placebo Comparator: Placebo<br> | Drug: PL-3994<br>* subcutaneous PL-3994, single dose, 4 escalating dose groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Forced Expiratory Volume in one second (FEV1) | Serial spirometry measures, including FEV1, assessed at specified time periods over 12 hours post dose. | Throughout 12 hours post dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Forced Vital Capacity (FVC) | Serial spirometry measures, including FVC, assessed at specified time periods over 12 hours post dose. | Throughout 12 hours post dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma