Clinical trial NCT02948582: Assessment of the Safety and Ability of a Once-a-day Dose of an Orally Inhaled Medicine [i.e., Glycopyrrolate Inhalation Solution = GIS] to Improve Airflow in the Lungs When Delivered Using an eFlow Nebulizer in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: Randomized, Placebo-Controlled, Double-Blind, Dose Ranging, Single-Dose, 6-Way Crossover Study to Assess Safety, Efficacy and Pharmacokinetics of EP-101 Using eFlow Nebuliser in Patients With COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Chronic Obstructive Pulmonary Disease
COPD
Emphysema
Chronic bronchitis
Lead sponsor: Sunovion Respiratory Development Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-28
Enrollment: 42
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 study assessed the safety and ability of an orally inhaled medicine \[i.e., Glycopyrrolate Inhalation Solution = GIS\] to improve airflow in the lungs when delivered using an eFlow nebulizer in 42 patients with Chronic Obstructive Pulmonary Disease (COPD). Each patient randomly received several, single doses of GIS, or placebo, separated by approximately 1 to 2 weeks. After the dose was given, lung airflow was measured over 24 hours and blood was collected to measure how much GIS was in the bloodstream. The study was conducted to find the once-a- day GIS dose that produced the highest improvement in lung airflow using the eFlow nebulizer.


Eligibility criteria: Inclusion Criteria:

1. Male and female patients aged 40 through 75 years, inclusive
2. A clinical diagnosis of COPD according to the GOLD guidelines
3. Current smokers or ex-smokers with at least 10 pack-year smoking history (e.g., at least 1 pack/day for 10
4. Post-bronchodilator FEV1 30-70% of predicted normal at the Screening Visit
5. Post-bronchodilator FEV1/FVC ratio \< 0.70 at the Screening Visit
6. Improvement in FEV1 \>12% and 150 mL following inhalation of ipratropium bromide at the Screening Visit
7. Ability to perform reproducible spirometry according to the ATS/ERS guidelines
8. Willing to stay at the study site for approximately 30 hours on each treatment visit
9. Willing and able to provide written informed consent

Exclusion Criteria:

1. Females who are pregnant or lactating at the Screening Visit, or if of childbearing potential not using one of the following acceptable means of birth control throughout the study:

   * Abstinence
   * Post-menopausal for at least two years
   * Surgically sterile (i.e., tubal ligation, hysterectomy)
   * Oral contraceptives (taken for at least one month prior to the Screening Visit)
   * Approved implantable or injectable contraceptives (e.g., Norplant®, Depo-Provera® or equivalent)
   * Barrier methods (e.g., condoms with spermicide)
   * Intrauterine device (i.e., IUD)
   * Vasectomy of male partner
   * Non-heterosexual life style
2. Current evidence or recent history of any clinically significant disease (other than COPD) or abnormality in the opinion of the Investigator that would put the subject at risk or which would compromise the quality of the study data; including but not limited to cardiovascular disease, myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes, neurologic or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities
3. Recent history of hospitalization due to an exacerbation of airway disease within 3 months or need for increased treatments for COPD within 6 weeks prior to the Screening Visit
4. Primary diagnosis of asthma
5. Prior lung volume reduction surgery or history of chest/lung irradiation
6. Regular use of daily oxygen therapy
7. Use of systemic (eg, intramuscular or intravenous) steroids within 3 months prior to the Screening Visit
8. Respiratory tract infection within 6 weeks prior to the Screening Visit
9. History of tuberculosis, bronchiectasis or other non- specific pulmonary disease
10. History of urinary retention or bladder neck obstruction type symptoms
11. History of narrow-angle glaucoma
12. Clinically significant abnormal ECG
13. Positive Hepatitis B surface antigen or positive Hepatitis C antibody
14. Positive screening test for HIV antibodies
15. Current or recent history (previous 12 months) of excessive use or abuse of alcohol
16. Current evidence or history of abusing legal drugs or use of illegal drugs or substances
17. Donation of 450 mL of blood within 8 weeks of the Screening Visit
18. History of hypersensitivity or intolerance to aerosol medications
19. Participation in another investigational drug study was received within 30 days prior to the Screening Visit

Primary outcomes:
measure: Trough FEV1 (Change From Baseline)
timeFrame: 24hr post dose
measure: Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline).
timeFrame: 0-12h post dose
measure: Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline).
timeFrame: 12-24h post dose
measure: Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline)
timeFrame: 0 to 24h
measure: Peak FEV1 (Change From Baseline and Percent Change)
timeFrame: 0-4h post dose
Secondary outcomes:
measure: Cmax; Maximum Observed Plasma Concentration
timeFrame: 0 to 12 hour
measure: Tmax; Time to Maximum Observed Plasma Concentration
timeFrame: 0 to 12 hours
measure: t1/2; Plasma Half-life
timeFrame: 0 to 12 hour
measure: AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration.
timeFrame: 0 to 12 hour
measure: AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity
timeFrame: 0 to 12 hour
measure: Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE
timeFrame: Day 69 (includes dosing Day 1, washout Day 12, safety follow up Day 69)
measure: Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study
timeFrame: 0-24 h
measure: Number of Clinically Significant Abnormal Laboratory Results Reported During the Study
timeFrame: Day -14, Day 69
measure: Number of Subjects With Clinically Significant ECG Parameters Reported During the Study
timeFrame: 0 to 24h
measure: Percentage of Subjects With Treatment Emergent AEs
timeFrame: Day 69 (includes dosing Day 1, washout Day 12, safety follow up Day 69)
Other outcomes:
Locations:
Study officials:
affiliation: Elevation Pharmaceuticals, Inc., (now known as Sunovion Respriatory Developement Inc.)
name: Ahmet Tutuncu, MD, PhD
role: STUDY_CHAIR
References:
citation: Leaker BR, Barnes PJ, Jones CR, Tutuncu A, Singh D. Efficacy and safety of nebulized glycopyrrolate for administration using a high efficiency nebulizer in patients with chronic obstructive pulmonary disease. Br J Clin Pharmacol. 2015 Mar;79(3):492-500. doi: 10.1111/bcp.12517.