Study to Determine the Amount of Glycopyrrolate Absorbed in the Lungs After Taking the Medicine With a eFlow Nebulizer and Seebri® Breezhaler® With and Without Activated Charcoal in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD). (GOLDEN7)

Sunovion

Status and phase: Completed; Phase 1

Conditions: COPD

Treatments: Drug: SUN-101 via eFlow nebulizer with activated charcoal; Drug: Seebri® Breezhaler®; Drug: Seebri® Breezhaler® with activated charcoal; Drug: SUN-101 via eFlow nebulizer; Drug: Glycopyrrolate Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT02512302

SUN101-105

Details and patient eligibility

About

The purpose of this research study is to determine the amount of medicine absorbed in the lungs following dosing via eFlow nebulizer and Seebri® Breezhaler® with and without activated charcoal in subjects with moderate to severe chronic obstructive pulmonary disease (COPD).

Full description

This is a randomized, open-label, single-dose per dosing period, five-way crossover study in subjects 40 to 70 years of age with a diagnosis of moderate to severe COPD per Global Initiative for Chronic Obstructive Lung Disease guidelines. After a subject provides consent for study participation, there will be a Screening Period lasting up to 3 weeks to determine study eligibility and to allow for appropriate washout of prohibited medications.

Eligible subjects will be randomized to one of 10 treatment Sequences. There will be a minimum of a 7-day washout period between each treatment visit. At each visit, subjects will receive one dose of study medication according to the sequence assigned.

Subjects with a ≥ 20% decrease in forced expiratory volume in one second (FEV1) based on review of the Visit predose value compared with the Screening value will be evaluated by the investigator for continuation in the study.

Subjects taking theophylline will not be able to participate in the study.

Enrollment: 30 patients

Sex: All

Ages: 40 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female patients 40 to 70 years-old, inclusive.
2. A clinical diagnosis of moderate to severe COPD according to the GOLD 2014 guidelines.
3. Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, or equivalent).
4. Post-bronchodilator (following inhalation of ipratropium bromide) FEV1 ≥ 30% and ≤ 80% of predicted normal during the Screening Period.
5. Post-bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio ≤ 0.70 during the Screening Period.
6. Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and/or European Respiratory Society (ERS) guidelines (2005).
7. Subject, if female ≤ 70 years of age and of child bearing potential, must have a negative urine pregnancy test at Visit 1. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study and must use an acceptable method of birth control: a) an oral contraceptive, an intrauterine device (IUD), implantable contraceptive, transdermal or injectable contraceptive for at least 1 month prior to entering the study with continued use throughout the study and for thirty days following participation; b) barrier method of contraception, eg, condom and /or diaphragm with spermicide while participating in the study; and/or c) abstinence.
8. Willing and able to remain at the study site for at least 24 hours for each treatment day.
9. Willing and able to provide written informed consent.
10. Willing and able to attend all study visits and adhere to all study assessments and procedures.

Exclusion criteria

1. Severe comorbidities including unstable cardiac or pulmonary disease or any other medical conditions that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject, included but not limited to the following:

   • Unstable ischemic heart disease (diagnosis of myocardial infarction or admission for acute coronary syndrome) within 6 months of screening.
   • Unstable cardiac arrhythmia or heart failure (change in treatment plan) within 6 months.
   • Treatment for diabetes mellitus within 6 months of screening.

2. Current evidence or history of a clinically significant abnormality of cardiac rhythm and/or conduction findings.

3. Concomitant clinically significant respiratory disease other than COPD (eg, asthma, tuberculosis, bronchiectasis, or other non-specific pulmonary disease).

4. History of malignancy of any organ system treated or untreated within the past 5 years, with the exception of localized basal cell carcinoma of the skin.

5. Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to the Screening Period.

6. Use of daily oxygen therapy > 10 hours per day.

7. Use of oral, intravenous, or intramuscular steroids within 3 months prior to the Screening Period.

8. Respiratory tract infection within 6 weeks prior to or during the Screening Period.

9. Significant blood loss (> 500 mL) or donated blood within 60 days preceding screening or plans to donate blood within 60 days after completing the study.

10. History of or clinically significant ongoing bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within the previous 6 months.

11. History of narrow-angle glaucoma.

12. Prolonged QTc interval (> 450 msec for males and > 470 msec for females) during the Screening Period, or history of long QT syndrome.

13. Recent documented history (previous 12 months) of substance abuse.

14. .Positive urine drug screen at Visit 1 provided the subject is unable to produce a valid medical rationale for the test result (eg, prescription medication).

15. Positive HbsAg, Hepatitis C antibody, or HIV 1/2 antibody test at Screening.

16. History of hypersensitivity or intolerance to aerosol medications, β2-agonists, anticholinergics, or sympathomimetic amines.

17. Significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator.

18. Participation in another investigational drug study where drug was received within 30 days prior to the Screening Period, or current participation in another investigational drug trial in which study treatment is being administered, including a SUN-101 study

19. Previously received SUN-101 (active treatment; formerly known as EP-101).

20. Previously received any glycopyrrolate product within 28 days of Screening.

21. Subject is taking theophylline.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 5 patient groups

SUN-101 via eFlow nebulizer

Experimental group

Description:

50 mcg glycopyrrolate via Electronic Nebulizer

Treatment:

Drug: SUN-101 via eFlow nebulizer

SUN-101 via eFlow nebulizer with activated charcoal

Experimental group

Description:

50 mcg glycopyrrolate via Electronic Nebulizer with activated charcoal

Treatment:

Drug: SUN-101 via eFlow nebulizer with activated charcoal

Seebri® Breezhaler®

Active Comparator group

Description:

63 mcg glycopyrronium bromide (50 mcg glycopyrronium) via DPI

Treatment:

Drug: Seebri® Breezhaler®

Seebri® Breezhaler® with activated charcoal

Active Comparator group

Description:

: : 63 mcg glycopyrronium bromide (50 mcg glycopyrronium) via DPI with activated charcoal

Treatment:

Drug: Seebri® Breezhaler® with activated charcoal

: Glycopyrrolate Injection

Active Comparator group

Description:

50 mcg glycopyrrolate via IV infusion

Treatment:

Drug: Glycopyrrolate Injection