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

Phase 2

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: Ipratropium bromide Inhalation Solution via Handihaler® DPI
Drug: EP-101 via nebulizer (eFlow®) 25 ug
Drug: EP-101 via nebulizer (eFlow®) 200 ug
Drug: Tiotropium bromide via (Spiriva® Handihaler®)
Drug: Placebo EP-101
Drug: EP-101 via nebulizer (eFlow®) 50 ug
Drug: EP-101 via nebulizer (eFlow®) 100 ug

Registration Number: NCT01426009

Lead Sponsor: Sunovion Respiratory Development Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 140

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ipratropium bromide Inhalation Solution	Ipratropium bromide Inhalation Solution via Handihaler® DPI	Ipratropium bromide Inhalation Solution via Handihaler® DPI
EP-101 via nebulizer (eFlow®) 25 ug	EP-101 via nebulizer (eFlow®) 25 ug	EP-101 via nebulizer (eFlow®)
EP-101 via nebulizer (eFlow®) 200 ug	EP-101 via nebulizer (eFlow®) 200 ug	EP-101 via nebulizer (eFlow®)
Tiotropium bromide via (Spiriva® Handihaler®)	Tiotropium bromide via (Spiriva® Handihaler®)	Tiotropium bromide via (Spiriva® Handihaler®)
Placebo EP-101	Placebo EP-101	Placebo
EP-101 via nebulizer (eFlow®) 50 ug	EP-101 via nebulizer (eFlow®) 50 ug	EP-101 via nebulizer (eFlow®)
EP-101 via nebulizer (eFlow®) 100 ug	EP-101 via nebulizer (eFlow®) 100 ug	EP-101 via nebulizer (eFlow®)

Primary Outcome Measures

Name	Time	Method
Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1)	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.
Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7	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

Name	Time	Method
Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7)	Day 1 and Day 7	Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines
Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7)	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.
Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests	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.
Rescue Medication Use	Day 1 through Day 7	Mean number of puffs of daily rescue medication
Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7)	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.

Trial Locations

Locations (2): Elevation Investigational Site
🇬🇧
Manchester, United Kingdom
Elevation Investigational SIte
🇺🇸
Madisonville, Kentucky, United States