Clinical trial NCT02038829: A Dose-Range Finding Study of SUN-101 in Subjects With Moderate to Severe COPD
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COPD
Keywords: COPD
Lead sponsor: Sunovion Respiratory Development Inc.
Sponsor class: INDUSTRY
First posted: 2014-01-17
Enrollment: 96
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients 40 to 65 years-old, inclusive.
2. A clinical diagnosis of moderate to severe COPD according to the GOLD 2011 guidelines.
3. Current smokers or ex-smokers with at least 10 pack year smoking history (eg, at least 1 pack/day for 10 years, or equivalent).
4. Post bronchodilator (following inhalation of ipratropium bromide) FEV1 ≥ 40% and ≤ 70% of predicted normal during Screening.
5. Post bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio ≤ 0.70 during Screening.
6. Post bronchodilator (following inhalation of ipratropium bromide) improvement in FEV1 ≥ 12% and ≥ 100 mL during Screening.
7. Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005).
8. 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.
9. Willing and able to remain at the study site for at least 24 hours at Day 7 of each Treatment Period.
10. Willing and able to attend all study visits and adhere to all study assessments/procedures.
11. Willing and able to provide written informed consent

Exclusion Criteria:

1. 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.
2. Current evidence or history of a clinically significant abnormality of cardiac rhythm and/or conduction including Holter monitoring prior to randomization.
3. Primary diagnosis of asthma.
4. 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.
5. Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to Screening.
6. Use of daily oxygen therapy \> 10 hours per day.
7. Use of systemic steroids within 3 months prior to Screening.
8. Respiratory tract infection within 6 weeks prior to or during Screening.
9. History of tuberculosis, bronchiectasis or other non-specific pulmonary disease.
10. History of urinary retention or bladder neck obstruction type symptoms.
11. History of narrow angle glaucoma.
12. Prolonged QTcF interval (males \> 450 msec and females \>470 msec) during Screening, or history of long QT syndrome.
13. Recent history (previous 12 months) of excessive use or abuse of alcohol or narcotic/illegal drugs.
14. History of hypersensitivity or intolerance to aerosol medications, beta-2 agonists, or anticholinergics.
15. Participation in another investigational drug study where drug was received within 30 days prior to Screening, or current participation in another investigational drug trial.
16. Subject is a staff member of the clinical site or a relative of a clinical site staff member.

Primary outcomes:
measure: Change From Baseline in Trough FEV1 at Treatment Visit Day 7 Compared to Placebo.
timeFrame: Baseline and Day 7
Secondary outcomes:
measure: Standardized Change From Baseline in FEV1 AUC(0-12hours)
timeFrame: Day 7
measure: Number of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment)
timeFrame: Over 7 days
measure: Percentage of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment)
timeFrame: Over 7 days
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Charlotte
country: United States
facility: American Health Research, Inc.
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon, PC
state: Oregon
city: Easley
country: United States
facility: Palmetto Medical Research Associates, LLC
state: South Carolina
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research, Inc.
state: South Carolina
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Spartanburg
country: United States
facility: S. Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Union
country: United States
facility: CU Pharmaceutical Research
state: South Carolina
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: SUN101 Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: Donohue JF, Goodin T, Tosiello R, Wheeler A. Dose selection for glycopyrrolate/eFlow(R) phase III clinical studies: results from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) phase II dose-finding studies. Respir Res. 2017 Dec 4;18(1):202. doi: 10.1186/s12931-017-0681-z.