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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sunovion Respiratory Development Inc.
ClinicalTrials.gov Identifier:
NCT01426009
First received: August 29, 2011
Last updated: September 25, 2012
Last verified: September 2012
History of Changes
  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 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
Drug: Placebo EP-101
Drug: Tiotropium bromide
Drug: Ipratropium bromide
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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 in Subjects With Moderate to Severe COPD

Resource links provided by NLM:

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Time to ≥ 10% improvement in post-dose FEV1

  • Treatment responders [ Time Frame: Day 1 through Day 7 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Adverse events, vital signs, ECG and clinical laboratory tests

  • Rescue medication use [ Time Frame: Day 1 through Day 7 ] [ Designated as safety issue: No ]
    Mean number of puffs of daily rescue medication


Enrollment: 140
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: Nebulized EP-101 Drug: EP-101
EP-101 Dose 1 administered once daily for 7 days
Drug: EP-101
EP-101 Dose 2 administered once daily for 7 days
Drug: EP-101
EP-101 Dose 3 administered once daily for 7 days
Drug: EP-101
EP-101 Dose 4 administered once daily for 7 days
Active Comparator: Tiotropium bromide (Spiriva® Handihaler®) Drug: Tiotropium bromide
Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI
Active Comparator: Ipratropium bromide Inhalation Solution Drug: Ipratropium bromide
Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer
Placebo Comparator: Placebo EP-101 Drug: Placebo EP-101
Placebo EP-101 administered once daily for 7 days

Detailed Description:

This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, four-period, incomplete block design cross-over study using EP-101 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 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
Genders Eligible for Study:   Both
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
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

No publications provided

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: September 25, 2012
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sunovion Respiratory Development Inc.:
COPD

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Bromides
Ipratropium
Tiotropium
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
 Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Parasympatholytics

ClinicalTrials.gov processed this record on May 16, 2013