Study to Investigate the Dose Response, Safety and Efficacy of Nebulized EP-101(SUN101) in Patients With Chronic Obstructive Pulmonary Disease (COPD): GOLDEN-1 Study

• ClinicalTrials.gov Identifier: NCT01426009
• Recruitment Status: Completed
• First Posted: August 30, 2011
• Results First Posted: May 7, 2018
• Last Update Posted: May 9, 2018
• Sponsor: Sunovion Respiratory Development Inc.
• Information provided by (Responsible Party): Sunovion Respiratory Development Inc.

Study Description

Brief Summary:

The purpose of this study is to determine steady-state efficacy and dose response profile and to assess safety and pharmacokinetic profile of nebulized EP-101(SUN101) after 7-day dosing using an investigational high efficiency nebulizer (eFlow®) compared with placebo and two active comparators in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: EP-101 via nebulizer (eFlow®) 25 ug; Drug: EP-101 via nebulizer (eFlow®) 50 ug; Drug: EP-101 via nebulizer (eFlow®) 100 ug; Drug: Placebo EP-101; Drug: Tiotropium bromide via (Spiriva® Handihaler®); Drug: Ipratropium bromide Inhalation Solution via Handihaler® DPI; Drug: EP-101 via nebulizer (eFlow®) 200 ug	Phase 2

Detailed Description:

This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, four-period, incomplete block design cross-over study using EP-101(SUN101) and open-label active controls (tiotropium bromide and ipratropium bromide). The study population will consist of subjects of 40-75 years of age with moderate to severe COPD. Approximately 133 subjects diagnosed with moderate to severe COPD will be enrolled in order to achieve minimum 105 subjects completing the study.

Following a run-in phase, each subject will be randomly assigned to one of 7 treatment sequences,(96 sequences when order of administration is considered), with each sequence comprised of four 7-day Treatment Periods. There will be a washout period of 7 days between each Treatment Period. Study visits will be conducted on Days 1 and 7 of each Treatment Period, with an overnight stay required in the clinic during these visits. A Final Study Visit will be conducted 7 days following the last study treatment.

During each Treatment Period, study treatments will be administered once daily (QD), except for ipratropium inhalation solution, which will be administered three times daily (TID). EP-101 (SUN101)active and placebo treatments will be administered using an investigational high-efficiency eFlow® nebulizer. Tiotropium bromide (Spiriva®) will be administered in an open-label manner via Handihaler® dry-powder inhaler (DPI). Ipratropium bromide inhalation solution will be administered in an open-label manner via general purpose nebulizer.

This study was previously posted by Elevation Pharmaceuticals, Inc. On September 5, 2012, Elevation was acquired by merger with Sunovion Pharmaceuticals Inc. ("Sunovion"), which resulted in Elevation becoming a direct wholly-owned subsidiary of Sunovion. In conjunction with this acquisition, the name of Elevation has been changed to Sunovion Respiratory Development Inc.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Seven Arm, Four-Period Cross-over, Incomplete Block Design, 7-Day Dosing Study to Assess the Dose-Response, Safety, and Efficacy of EP-101 (SUN101) in Subjects With Moderate to Severe COPD
• Study Start Date: August 2011
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: EP-101 via nebulizer (eFlow®) 25 ug; EP-101 via nebulizer (eFlow®)	Drug: EP-101 via nebulizer (eFlow®) 25 ug; EP-101 (25 ug ) Dose 1 administered once daily for 7 days; Other Name: SUN101
Active Comparator: Tiotropium bromide via (Spiriva® Handihaler®); Tiotropium bromide via (Spiriva® Handihaler®)	Drug: Tiotropium bromide via (Spiriva® Handihaler®); Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI; Other Name: Tiotropium bromide
Active Comparator: Ipratropium bromide Inhalation Solution; Ipratropium bromide Inhalation Solution via Handihaler® DPI	Drug: Ipratropium bromide Inhalation Solution via Handihaler® DPI; Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer; Other Name: Ipratropium bromide
Placebo Comparator: Placebo EP-101; Placebo	Drug: Placebo EP-101; Placebo EP-101 administered once daily for 7 days; Other Name: Placebo
Experimental: EP-101 via nebulizer (eFlow®) 50 ug; EP-101 via nebulizer (eFlow®)	Drug: EP-101 via nebulizer (eFlow®) 50 ug; EP-101 (50 ug ) administered once daily for 7 days; Other Name: SUN101
Experimental: EP-101 via nebulizer (eFlow®) 100 ug; EP-101 via nebulizer (eFlow®)	Drug: EP-101 via nebulizer (eFlow®) 100 ug; EP-101 (100ug) administered once daily for 7 days; Other Name: SUN101
Experimental: EP-101 via nebulizer (eFlow®) 200 ug; EP-101 via nebulizer (eFlow®)	Drug: EP-101 via nebulizer (eFlow®) 200 ug; EP-101 (200) ug administered once daily for 7 days; Other Name: SUN101

Outcome Measures

Primary Outcome Measures :

1. Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Day 1 and Day 7 ]
   Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours post dose for Day 1 and Day 7 within each Treatment Period. 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. Change from baseline was calculated as the trough FEV1 value minus the baseline for Day 1 and Day 7.
2. Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 [ Time Frame: Day 1 and Day 7 ]
   Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. The standardized FEV1 AUC(0-12hr and 12-24hr) on Day 1 and Day 7 was calculated using the trapezoidal rule from the changes in FEV1 at Day 1 and Day 7, respectively, 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.

Secondary Outcome Measures :

1. Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) [ Time Frame: Day 1 and Day 7 ]
   Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines
2. Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) [ Time Frame: Day 1 and Day 7 ]
   Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Clinically meaningful is defined as when the change from baseline (mean of the two pre-dose values at Day 1) in 24 hour trough FEV1 on a SUN-101 treatment is more than 100 mL compared to the mean change in trough FEV1 from all subjects on the placebo treatment.
3. Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests [ Time Frame: Day 1 through Day 7 ]
   AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. Vital signs were performed during the screening period to confirm study eligibility and at the final study visit. ECGs were performed during the screening period to confirm study eligibility. Vital signs and ECG were additionally collected within 30 minutes pre-dose; and 30 minutes, and 1, 2, 4, 6, 12 hours, and 23 hours 45 minutes post-dose within each treatment period. Clinical laboratory assessments were conducted during the screening period, at each study visit during each treatment period, and at the final study visit.
4. Rescue Medication Use [ Time Frame: Day 1 through Day 7 ]
   Mean number of puffs of daily rescue medication
5. Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) [ Time Frame: Day 1 and Day 7 ]
   percentage of subjects with clinically meaningful change from pre-dose in trough FEV1 on Day 1 and Day 7 Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 40-75 years of age
• Clinical diagnosis of moderate to severe COPD
• Current/ex-smokers with at least 10 pack-year smoking history
• Post-bronchodilator FEV1 ≥ 30% and ≤ 70% predicted normal values
• Post-bronchodilator FEV1/FVC ratio of ≤ 0.70
• Post-bronchodilator improvement in FEV1 ≥ 12% and ≤ 30%, and a minimum of 100 mL
• Willing and able to remain at the study site for at least 24 hours at each study visit
• Signed written informed consent

Exclusion Criteria:

• Current evidence or recent history of any clinically significant and unstable disease or abnormality (e.g., myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes)
• Primary diagnosis of asthma
• History of malignancy within the past 5 years
• History of COPD exacerbation within 6 weeks of Screening
• Daily oxygen therapy > 10 hours per day
• Systemic steroids use within 6 weeks of Screening
• Respiratory tract infection within 6 weeks of Screening
• History of tuberculosis, bronchiectasis
• History of urinary retention or bladder neck obstruction type symptoms
• History of glaucoma
• Prolonged QTc interval (>460msec) or history of long QT syndrome
• Recent history of alcohol or drug abuse
• Females who are pregnant or breastfeeding, or if of child-bearing potential unwilling to practice acceptable birth control methods
• History of hypersensitivity or intolerance to aerosol medications
• Participation in another investigational drug study within 30 days of Screening

Contacts and Locations

Locations

United States, Arizona

Elevation Investigational Site

Phoenix, Arizona, United States, 85006

United States, California

Elevation Investigational Site

Los Angeles, California, United States, 90048

United States, Florida

Elevation Investigational Site

DeLand, Florida, United States, 32720

United States, Kentucky

Elevation Investigational SIte

Madisonville, Kentucky, United States, 42431

United States, Massachusetts

Elevation Investigational Site

North Dartmouth, Massachusetts, United States, 02747

United States, North Carolina

Elevation Investigational Site

Charlotte, North Carolina, United States, 28207

Elevation Investigational Site

Raleigh, North Carolina, United States, 27607

United States, Oregon

Elevation Investigational Site

Medford, Oregon, United States, 97504

United States, South Carolina

Elevation Investigational Site

Spartanburg, South Carolina, United States, 29303

United States, Washington

Elevation Investigational Site

Tacoma, Washington, United States, 98418

United Kingdom

Elevation Investigational Site

Manchester, United Kingdom, M21 8AD

Sponsors and Collaborators

Sunovion Respiratory Development Inc.

Investigators

• Study Director: Ahmet Tutuncu, M.D., Ph.D.; Chief Medical Officer / Elevation Pharmaceuticals, Inc.

More Information

• Responsible Party: Sunovion Respiratory Development Inc.
• ClinicalTrials.gov Identifier: NCT01426009
• Other Study ID Numbers: EP-101-03
• First Posted: August 30, 2011
• Results First Posted: May 7, 2018
• Last Update Posted: May 9, 2018
• Last Verified: May 2018

Keywords provided by Sunovion Respiratory Development Inc.:

COPD

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Bromides; Tiotropium Bromide; Ipratropium; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Parasympatholytics; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anticonvulsants