Clinical trial NCT01426009: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: Sunovion Respiratory Development Inc.
Sponsor class: INDUSTRY
First posted: 2011-08-30
Enrollment: 140
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Day 1 and Day 7
measure: Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7
timeFrame: Day 1 and Day 7
Secondary outcomes:
measure: Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7)
timeFrame: Day 1 and Day 7
measure: Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7)
timeFrame: Day 1 and Day 7
measure: Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests
timeFrame: Day 1 through Day 7
measure: Rescue Medication Use
timeFrame: Day 1 through Day 7
measure: Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7)
timeFrame: Day 1 and Day 7
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Elevation Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: Elevation Investigational Site
state: California
city: DeLand
country: United States
facility: Elevation Investigational Site
state: Florida
city: Madisonville
country: United States
facility: Elevation Investigational SIte
state: Kentucky
city: North Dartmouth
country: United States
facility: Elevation Investigational Site
state: Massachusetts
city: Charlotte
country: United States
facility: Elevation Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Elevation Investigational Site
state: North Carolina
city: Medford
country: United States
facility: Elevation Investigational Site
state: Oregon
city: Spartanburg
country: United States
facility: Elevation Investigational Site
state: South Carolina
city: Tacoma
country: United States
facility: Elevation Investigational Site
state: Washington
city: Manchester
country: United Kingdom
facility: Elevation Investigational Site
Study officials:
affiliation: Chief Medical Officer / Elevation Pharmaceuticals, Inc.
name: Ahmet Tutuncu, M.D., Ph.D.
role: STUDY_DIRECTOR
References: