A Long-Term Safety Trial of Treatment With Nebulized SUN-101 in Patients With COPD

Study Overview
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Brief Summary
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This is a long-term safety trial of 48 weeks. Eligible subjects will enter the 48-week, open-label treatment period to receive one of two treatments (SUN-101 given as 50 mcg twice a day or Spiriva® [tiotropium] given as 18 mcg once a day).

Detailed Description
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This is a Phase 3, randomized, open-label, active-controlled, parallel-group, multicenter, long-term safety trial of 48 weeks of treatment with nebulized SUN-101 using an Investigational eFlow® Closed System (CS) nebulizer or Spiriva in approximately 1050 subjects with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) guidelines. Eligible subjects will enter the 48-week, open-label treatment period following randomization to receive one of two treatments (SUN-101 given as 50 mcg BID or Spiriva® [tiotropium] given as 18 mcg QD). The hypothesis for this study is that the incidence of treatment-emergent adverse events reported over the course of 48 weeks of treatment by subjects randomized to SUN-101 is numerically similar to the incidence of treatment-emergent adverse events reported over the course of 48 weeks of treatment by subject randomized to Spiriva (tiotropium).

Official Title
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A Randomized, Open-Label, Active-Controlled, Parallel-Group, Multicenter, Long-Term Safety Trial of Treatment With Nebulized SUN-101 in Patients With COPD: GOLDEN-5 (Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer)

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: SUN-101 50 mcg BID eFlow (CS) nebulizer
* Drug: Spiriva® 18 mcg QD Handihaler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients age ≥ 40 years, inclusive. A clinical diagnosis of COPD according to the GOLD 2014 guidelines. Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, or equivalent). Post-bronchodilator (following inhalation of ipratropium bromide) FEV1 < 80% of predicted normal and > 0.7 L during Screening (Visit 1). Post-bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio < 0.70 during Screening (Visit 1). Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005). Subject, if female ≤ 65 years of age and of child bearing potential, must have a negative serum pregnancy test at Visit 1. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study and must use an acceptable method of birth control: a) an oral contraceptive, an intrauterine device (IUD), implantable contraceptive, transdermal or injectable contraceptive for at least 1 month prior to entering the study with continued use throughout the study and for thirty days following participation; b) barrier method of contraception, e.g., condom and /or diaphragm with spermicide while participating in the study; and/or c) abstinence.. Willing and able to provide written informed consent. Willing and able to attend all study visits and adhere to all study assessments and procedures. Exclusion Criteria: Severe comorbidities including unstable cardiac or pulmonary disease or any other medical conditions that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject. Concomitant clinically significant respiratory disease other than COPD (eg, asthma, tuberculosis, bronchiectasis or other non-specific pulmonary disease). Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to Screening (Visit 1). Use of daily oxygen therapy > 12 hours per day. Respiratory tract infection within 6 weeks prior to Screening (Visit 1). Use of systemic steroids within 3 months prior to Screening (Visit 1). History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localized basal cell carcinoma of the skin. Prolonged QTc (> 450 msec for males and > 470 msec for females) during Screening (Visit 1), or history of long QT syndrome. History of or clinically significant ongoing bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within the previous 6 months. History of narrow angle glaucoma. History of hypersensitivity or intolerance to aerosol medications. Recent documented history (within the previous 3 months) of substance abuse. Significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator. Participation in another investigational drug study where drug was received within 30 days prior to Screening (Visit 1) or current participation in another investigational drug trial, including a SUN-101 study. Previously received SUN-101 (active treatment; formerly known as EP-101). Contraindicated for treatment with, or having a history of reactions/ hypersensitivity to anticholinergic agents, beta2 agonists, or sympathomimetic amines.

Ages Eligible for Study
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Minimum Age: 40 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SUN-101 50 mcg BID eFlow (CS) nebulizer<br>SUN-101 (Glycopyrrolate) 50 mcg twice daily (BID) via eFlow Closed System (CS) nebulizer | Drug: SUN-101 50 mcg BID eFlow (CS) nebulizer<br>* SUN-101 (Glycopyrrolate) 50 mcg twice daily (BID) via eFlow Closed System (CS) nebulizer<br>* Other names: Glycopyrrolate;|
| Active Comparator: Spiriva 18 mcg QD Handihaler<br>Spiriva (tiotropium) 18 mcg once daily (QD) via Handihaler | Drug: Spiriva® 18 mcg QD Handihaler<br>* Spiriva (tiotropium) 18 mcg once daily (QD) via Handihaler<br>* Other names: (tiotropium);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment-emergent Adverse Events (TEAE) | A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date. | Up to Week 48 | 
| Percentage of Subjects With Treatment-emergent Adverse Events | A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date. | Up to Week 48 | 
| Number of Subjects With Treatment-emergent Serious Adverse Events (SAE) | A treatment emergent serious adverse event (SAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date. | Up to Week 48 | 
| Percentage of Subjects With Treatment-emergent Serious Adverse | A treatment emergent serious adverse event (SAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date. | Up to Week 48 | 
| Number of Subjects Who Discontinue the Study Due to TEAE | A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date. | Up to Week 48 | 
| Percentage of Subjects Who Discontinue the Study Due to TEAE | A TEAE is any adverse event (AE) that occurred on or after the first dose of study medication, any AE with a missing start date and a stop date on or after the first dose of study medication, or any AE with both a missing start and stop date. | Up to 48 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact. | Up to Week 48 | 
| Percentage of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact. | Up to 48 Weeks | 
| Incidence Rate Per 1000 Person Years of Subjects With Major Adverse Cardiac Events (MACE), Including Cardiovascular Death, Ischemia/Infarction, and Stroke | All deaths and any other findings suggestive of a potential MACE (including clinically relevant information and SAEs, and all PTs form the SMQs myocardial infarction, other ischemic heart disease, central nervous system hemorrhages and cerebrovascular conditions) were sent to an adjudication committee for review and categorized as CV death, nonfatal MI, and nonfatal stroke. The MACE score was defined as the total number of subjects with CV deaths, nonfatal MIs, and nonfatal strokes. These events were collected from the first date of study medication until the date of last contact. | up to week 48 | 
| Mean Change From Baseline Over 48 Weeks in Trough FEV1 for All Subjects | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the average of the FEV1 values collected at the end of the dosing interval at each clinic visit. The mean change from baseline in trough FEV1 over the 48 week treatment period is calculated by averaging the trough FEV1 changes from baseline across all study visits while subjects are taking randomized treatment. Values affected by other medication use were to be set to missing. | Up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, COPD