A Dose-Range Finding Study of SUN-101 in Subjects With Moderate to Severe COPD

Study Overview
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Brief Summary
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Study for subjects 40 to 65 years-old with a diagnosis of moderate to severe COPD. Aclidinium bromide 400 mcg 2x a day will be given as an active comparator.

Detailed Description
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This is a randomized, six-way crossover study to determine the efficacy and dose-response profile of SUN101. The study population will consist of subjects 40 to 65 years-old (inclusive), with a diagnosis of moderate to severe COPD. Aclidinium bromide 400 mcg bid will be given as an active comparator. The study will be double-blind for SUN-101 and placebo and will be open-label for aclidinium.

Official Title
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A Dose-Range Finding Study of SUN-101 in Subjects With Moderate to Severe COPD: GOLDEN 6 (Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer)

Conditions
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COPD

Intervention / Treatment
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* Drug: Placebo
* Drug: SUN101 3 mcg
* Drug: SUN-101 6.25 mcg
* Drug: SUN-101 12.5 mcg
* Drug: SUN-101 50 mcg
* Drug: Aclidinium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 40 to 65 years-old, inclusive. A clinical diagnosis of moderate to severe COPD according to the GOLD 2011 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 ≥ 40% and ≤ 70% of predicted normal during Screening. Post bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio ≤ 0.70 during Screening. Post bronchodilator (following inhalation of ipratropium bromide) improvement in FEV1 ≥ 12% and ≥ 100 mL during Screening. Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005). Female of child bearing potential (only) must have a negative serum pregnancy test at Screening and be neither breastfeeding nor intending to become pregnant during study participation. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study. Female subjects of child bearing potential must use an adequate method of birth control from Screening until 30 days after receiving study drug and use contraception in addition to their partners using a barrier method. Acceptable forms of contraception are as follows: Abstinence Barrier methods: condoms, diaphragms, cervical caps; with a spermicide foam, gel, film, cream or suppository; Oral contraceptives Non hormone containing intrauterine methods: intrauterine devices or systems. Willing and able to remain at the study site for at least 24 hours at Day 7 of each Treatment Period. Willing and able to attend all study visits and adhere to all study assessments/procedures. Willing and able to provide written informed consent Exclusion Criteria: Current evidence or recent history of any clinically significant and unstable disease (other than COPD) or abnormality in the opinion of the Investigator that would put the subject at risk or which would compromise the quality of the study data; including but not limited to cardiovascular disease, myocardial infarction, cardiac failure, uncontrolled hypertension, life threatening arrhythmias, uncontrolled diabetes, neurologic or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities. Current evidence or history of a clinically significant abnormality of cardiac rhythm and/or conduction including Holter monitoring prior to randomization. Primary diagnosis of asthma. 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. Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to Screening. Use of daily oxygen therapy > 10 hours per day. Use of systemic steroids within 3 months prior to Screening. Respiratory tract infection within 6 weeks prior to or during Screening. History of tuberculosis, bronchiectasis or other non-specific pulmonary disease. History of urinary retention or bladder neck obstruction type symptoms. History of narrow angle glaucoma. Prolonged QTcF interval (males > 450 msec and females >470 msec) during Screening, or history of long QT syndrome. Recent history (previous 12 months) of excessive use or abuse of alcohol or narcotic/illegal drugs. History of hypersensitivity or intolerance to aerosol medications, beta-2 agonists, or anticholinergics. Participation in another investigational drug study where drug was received within 30 days prior to Screening, or current participation in another investigational drug trial. Subject is a staff member of the clinical site or a relative of a clinical site staff member.

Ages Eligible for Study
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Minimum Age: 40 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo bid | Drug: Placebo<br>* Placebo<br>|
| Experimental: SUN-101 3 mcg<br>SUN-101 3 mcg bid | Drug: SUN101 3 mcg<br>* SUN-101 3 mcg bid<br>|
| Experimental: SUN-101 6.25 mcg<br>SUN-101 6.25 mcg bid | Drug: SUN-101 6.25 mcg<br>* SUN-101 6.25 mcg bid<br>|
| Experimental: SUN-101 12.5 mcg<br>SUN-101 12.5 mcg bid | Drug: SUN-101 12.5 mcg<br>* SUN-101 12.5 mcg bid<br>|
| Experimental: SUN-101 50 mcg<br>SUN-101 50 mcg bid | Drug: SUN-101 50 mcg<br>* SUN-101 50 mcg bid<br>|
| Active Comparator: Aclidinium 400 mcg<br>Aclidinium 400 mcg bid | Drug: Aclidinium<br>* Aclidinium 400 mcg bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough FEV1 at Treatment Visit Day 7 Compared to Placebo. | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the average of the 2 spirometry values collected at 23 hours 15 minutes, and 23 hours 45 minutes post-morning dose on Day 7 of each Treatment Period. The FEV1 values within 6 hours after the use of rescue medication were considered as missing. Baseline was calculated as the mean of the FEV1 values at 45 minutes and 15 minutes prior to the morning dose at Day 1 of each Treatment Period | Baseline and Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized Change From Baseline in FEV1 AUC(0-12hours) | The standardized FEV1 AUC(0-12) on Day 7 was calculated using the trapezoidal rule from the changes in FEV1 from the baseline value (the mean of the two FEV1 values at 45 minutes and 15 minutes prior to morning dose at Day 1 of the respective Treatment Periods) and dividing by the actual length of the time interval). | Day 7 | 
| Number of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment) | A treatment emergent adverse event (TEAE) is any TEAE 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 TEAE with both a missing start and stop date. | Over 7 days | 
| Percentage of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment) | A treatment emergent adverse event (TEAE) is any TEAE 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 TEAE with both a missing start and stop date. | Over 7 days | 

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