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 - Full Text View

Purpose

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	Intervention	Phase
Chronic Obstructive Pulmonary Disease	Drug: EP-101 via nebulizer (eFlow®) Drug: Placebo EP-101 Drug: Tiotropium bromide via (Spiriva® Handihaler®) Drug: Ipratropium bromide Inhalation Solution via Handihaler® DPI	Phase 2


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: COPD Lung Diseases

U.S. FDA Resources

Further study details as provided by Sunovion Respiratory Development Inc.:

Primary Outcome Measures:

Trough Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Day 1 through Day 7 ]
Mean change in 24-hour post-dose trough FEV1 on Day 1 and Day 7
FEV1 area under the curve (AUC) [ Time Frame: Day 1 through Day 7 ]
Standardized change in FEV1 AUC (0-12hr and 12-24hr) on Day 1 and Day 7

Secondary Outcome Measures:

Peak FEV1 [ Time Frame: Day 1 through Day 7 ]
Maximum FEV1 during the first 4 hours post-dose on Day 1 and Day 7
Time to onset of action [ Time Frame: Day 1 through Day 7 ]
Time to ≥ 10% improvement in post-dose FEV1
Treatment responders [ Time Frame: Day 1 through Day 7 ]
Proportion of subjects with clinically meaningful change from pre-dose in trough FEV1 on Day 1 and Day 7
Safety and tolerability of EP-101 [ Time Frame: Day 1 through Day 7 ]
Adverse events, vital signs, ECG and clinical laboratory tests
Rescue medication use [ Time Frame: Day 1 through Day 7 ]
Mean number of puffs of daily rescue medication


Enrollment:	275
Study Start Date:	August 2011
Study Completion Date:	December 2011
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®)	Drug: EP-101 via nebulizer (eFlow®) EP-101 Dose 1 administered once daily for 7 days Other Name: SUN101 Drug: EP-101 via nebulizer (eFlow®) EP-101 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

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, 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


Ages Eligible for Study:	40 Years to 75 Years (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01426009

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 History of Changes
Other Study ID Numbers:	EP-101-03
Study First Received:	August 29, 2011
Last Updated:	June 7, 2016

Keywords provided by Sunovion Respiratory Development Inc.:


COPD

Additional relevant MeSH terms:


Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases Pharmaceutical Solutions Tiotropium Bromide Ipratropium Bromides 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

ClinicalTrials.gov processed this record on August 21, 2017