Assessment of the Safety and Ability of a Once-a-day Dose of an Orally Inhaled Medicine [ie, Glycopyrrolate Inhalation Solution = GIS] to Improve Airflow in the Lungs When Delivered With an Electronic eFlow Nebulizer System in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Sunovion Respiratory Development Inc.12 enrolled

Overview

The study assessed the safety and ability of several doses of an orally inhaled medicine \[ie, Glycopyrrolate Inhalation Solution = GIS\] to improve airflow in the lungs when delivered with an electronic eFlow nebulizer system in patients with Chronic Obstructive Pulmonary Disease (COPD). The study was conducted in 12 patients in 2 parts. Part 1 was designed to find the once-a- day GIS dose that produced the highest improvement in lung airflow. Part 2 tested the GIS dose with the highest improvement in lung airflow and a placebo (ie, no drug) delivered by a general purpose nebulizer. The airflow improvements of the same GIS dose were compared between the two nebulizer systems to determine what effect the device had on GIS delivery.

In Part I, 12 subjects were randomly allocated to one of 2 cohorts, running in parallel. The 6 cohort 1 subjects received 25 mg and then 200 mg during their treatment periods 1 and 2, respectively. The 6 cohort 2 subjects received 75mg, 500mg, and 1000 mg during their treatment periods 1, 2, and 3, respectively. During Part II of the study, the same 12 subjects from Part I were randomized to receive either 200 mg jet or placebo in a 1:1 ratio.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Chronic Obstructive Pulmonary Disease

Eligibility

Sex: ALLMin age: 40 YearsMax age: 75 Years

Medical Language ↔ Plain English

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 years, or 10 packs/day for 1 year) 4. Post-bronchodilator FEV1 40-80% of predicted normal 5. Post-bronchodilator FEV1/FVC ratio \< 0.70 6. Improvement in FEV1 \>12% (minimum 150 mL) following inhalation of ipratropium bromide 7. Ability to perform reproducible spirometry according to the ATS/ERS guidelines 8. If female and of childbearing potential, must have had a negative pregnancy test and was not lactating at the Screening Visit, and was using one of the following acceptable means of birth control throughout the study: * Post-menopausal for at least two years * Surgically sterile * 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 9. Willing and able to provide written informed consent Exclusion Criteria: 1. 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 patients at risk or which would compromise the quality of the study data; including but not limited to cardiovascular disease, myocardial infraction, hypertension, arrhythmia, diabetes, neurological or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities. 2. Recent history of an exacerbation of airway disease within 3 months or need for increased treatments for COPD within 6 weeks prior to the Screening Visit. 3. Regular use of daily oxygen therapy. 4. Use of systemic (e.g., intramuscular or intravenous) steroids within 3 months prior to the Screening Visit 5. Respiratory tract infection within 6 weeks prior to the Screening Visit 6. History of tuberculosis, bronchiectasis or other non-specific pulmonary disease 7. History of urinary retention or bladder neck obstruction type symptoms 8. History of narrow-angle glaucoma 9. Current or recent history (previous 12 months) of excessive use or abuse of alcohol 10. Current evidence or history of abusing legal drugs or the use of illegal drugs or substances 11. History of hypersensitivity or intolerance to aerosol medications 12. Participation in another investigational drug study where drug was received within 30 days prior to the Screening Visit

Outcomes

Primary Outcomes

Number of Subjects Who Died

Time frame: 0-47 days

Number of Subjects With Treatment Emergent SAEs

AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. SAEs are AEs that result in the following outcomes: death, are life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may have been considered a SAE when, based upon appropriate medical judgment, they may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition.

Time frame: 0-47 days

Number of Subjects Who Discontinued Due to AE

AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.

Time frame: 0-47 days

Percentage of Subjects With Treatment Emergent AEs

AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.

Time frame: 0-47 days

Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study

Vital signs were measured at screening, during the study (pre-dose, and 30 and 60 minutes and 2, 4, 8, 12, 24 and 30 hours post-dose) and at post study assessment. The clinical significance of each out of normal range vital sign parameter was determined by the investigator during the study.

Time frame: 30 hrs post dose

Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study

Clinical safety lab parameters were collected at screening and at the post study follow-up assessment. The clinical significance of each out of normal range laboratory parameter was determined by the investigator during the study.

Time frame: day 47 (post studyfollow-up assessment)

Number of Subjects With Clinically Significant ECG Parameters Reported During the Study

ECGs were measured at screening, during the study (pre-dose, and 30 and 60 minutes and 2, 4, 8, 12, 24 and 30 hours post-dose) and at post study follow-up assessment.

Time frame: 30hr post dose

Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study

Time frame: post study follow-up assessment (Day 47)

Number of Subjects With Treatment Emergent AEs

AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. SAEs are AEs that result in the following outcomes: death, are life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may have been considered a SAE when, based upon appropriate medical judgment, they may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition.

Time frame: 0-47 days

Secondary Outcomes

Trough FEV1 (Change From Baseline)

Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the spirometry value collected at 24 hours post dose within each Treatment Period.

Time frame: 24hr post dose

Peak FEV1 (Percent Change)

Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.

Time frame: 0 to 4hr

Peak FEV1 (Change From Baseline )

Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.

Time frame: 0 to 4hr

FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline)

Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.

Time frame: 0 to 24hr post dose

Cmax Maximum Observed Plasma Concentration

Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr

Time frame: 0 to 12 hours post dose

Tmax Time to Maximum Observed Plasma Concentration

Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr

Time frame: 0 to 12 hours post dose

AUC0-t Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration

Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr

Time frame: 0 to 12 hourr post dose

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

Assessment of the Safety and Ability of a Once-a-day Dose of an Orally Inhaled Medicine [ie, Glycopyrrolate Inhalation Solution = GIS] to Improve Airflow in the Lungs When Delivered With an Electronic eFlow Nebulizer System in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes