A Dose-Range Finding Study of SUN-101 in Subjects With Moderate to Severe COPD (GOLDEN 6)

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 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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • American Health Research, Inc.
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon, PC
  • South Carolina
    • Easley, South Carolina, United States, 29640
      • Palmetto Medical Research Associates, LLC
    • Greenville, South Carolina, United States, 29615
      • Upstate Pharmaceutical Research
    • Greenville, South Carolina, United States, 29615
      • Greenville Pharmaceutical Research, Inc.
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
    • Spartanburg, South Carolina, United States, 29303
      • S. Carolina
    • Union, South Carolina, United States, 29379
      • CU Pharmaceutical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sunovion Respiratory Development Inc.
• Investigators: Study Director: SUN101 Medical Director, MD, Sunovion

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: January 15, 2014
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (Estimate): January 17, 2014

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: March 12, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: COPD
• Other Study ID Numbers: SUN101-201