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)

NCT02948582 | Completed Phase 2 Results

• 2 other identifiers: EP-101-022010-018987-17
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive Pulmonary Disease; COPD; Emphysema; Chronic bronchitis

Outcome Measures

Primary Outcomes (5)

• Trough FEV1 (Change From Baseline)

  Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of FEV1 values obtained at 23 hours 30 minutes and 24 hours post-dose of each Treatment Visit.

  24hr post dose

• Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline).

  Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.. The standardized actual FEV1 AUC(0-12) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(0-12) was also calculated similarly, using the change from pre-dose FEV1.

  0-12h post dose

• Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline).

  Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. The standardized actual FEV1 AUC(12-24) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(12-24) was also calculated similarly, using the change from pre-dose FEV1.

  12-24h post dose

• Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline)

  Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. . The standardized actual FEV1 AUC(0-24) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(0-24) was also calculated similarly, using the change from pre-dose FEV1.

  0 to 24h

• Peak FEV1 (Change From Baseline and Percent Change)

  spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. . The peak FEV1 was defined as the highest post-dose FEV1 value within 4 hrs after the dose. Percent change from baseline was calculated as 100 times the difference of peak FEV1 minus baseline FEV1 divided by baseline FEV1.

  0-4h post dose

Secondary Outcomes (10)

• Cmax; Maximum Observed Plasma Concentration

  0 to 12 hour

• Tmax; Time to Maximum Observed Plasma Concentration

  0 to 12 hours

• t1/2; Plasma Half-life

  0 to 12 hour

• AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration.

  0 to 12 hour

• AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity

  0 to 12 hour

Study Arms (6)

Glycopyrrolate Inhalation Solution12.5μg

EXPERIMENTAL

Glycopyrrolate Inhalation Solution12.5μg via e-flow nebulizer, once daily

Drug: Glycopyrrolate Inhalation Solution12.5μg

Glycopyrrolate Inhalation Solution 50μg

EXPERIMENTAL

Glycopyrrolate Inhalation Solution 50mg via e-flow nebulizer, once daily

Drug: Glycopyrrolate Inhalation Solution 50μg

Glycopyrrolate Inhalation Solution 100μg

EXPERIMENTAL

Glycopyrrolate Inhalation Solution 100μg via e-flow nebulizer, once daily

Drug: Glycopyrrolate Inhalation Solution 100μg

Glycopyrrolate Inhalation Solution 200μg

EXPERIMENTAL

Glycopyrrolate Inhalation Solution 200μg via e-flow nebulizer, once daily

Drug: Glycopyrrolate Inhalation Solution 200μg

Glycopyrrolate Inhalation Solution 400μg

EXPERIMENTAL

Glycopyrrolate Inhalation Solution 400μg via e-flow nebulizer, once daily

Drug: Glycopyrrolate Inhalation Solution 400μg

Placebo 0.5mL

PLACEBO COMPARATOR

Placebo 0.5mL via e-flow nebulizer, once daily

Drug: Placebo 0.5mL

Interventions

Glycopyrrolate Inhalation Solution12.5μg DRUG

Glycopyrrolate Inhalation Solution12.5μg via eFlow, once daily

Also known as: GIS

Glycopyrrolate Inhalation Solution12.5μg

Glycopyrrolate Inhalation Solution 50μg DRUG

Glycopyrrolate Inhalation Solution 50μg via eFlow, once daily

Also known as: GIS

Glycopyrrolate Inhalation Solution 50μg

Glycopyrrolate Inhalation Solution 100μg DRUG

Glycopyrrolate Inhalation Solution 100μg via eFlow, once daily

Also known as: GIS

Glycopyrrolate Inhalation Solution 100μg

Glycopyrrolate Inhalation Solution 200μg DRUG

Glycopyrrolate Inhalation Solution 200μg via eFlow, once daily

Also known as: GIS

Glycopyrrolate Inhalation Solution 200μg

Glycopyrrolate Inhalation Solution 400μg DRUG

Glycopyrrolate Inhalation Solution 400μg via eFlow, once daily

Also known as: GIS

Glycopyrrolate Inhalation Solution 400μg

Placebo 0.5mL DRUG

Placebo 0.5mL via eFlow, once daily

Also known as: Placebo

Placebo 0.5mL

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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
• 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
• Primary diagnosis of asthma
• Prior lung volume reduction surgery or history of chest/lung irradiation
• Regular use of daily oxygen therapy

Sponsors & Collaborators

• Sunovion Respiratory Development Inc.: lead

Related Publications (1)

• 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.

  PMID: 25243340 RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema; Bronchitis, Chronic

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases

Results Point of Contact

• Title: Respiratory Medical Director
• Organization: Sunovion Pharmaceuticals Inc.

1-866-503-6351

Study Officials

• Ahmet Tutuncu, MD, PhD

  Elevation Pharmaceuticals, Inc., (now known as Sunovion Respriatory Developement Inc.)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: October 28, 2016
• Study Start: July 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: March 12, 2018
• Results First Posted: March 12, 2018

Record last verified: 2018-03