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).

NCT02512302 | Completed Phase 1 Results

• 1 other identifier: SUN101-105
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

COPD

Keywords

COPD

Outcome Measures

Primary Outcomes (3)

• Cmax

  maximum observed concentration-Cmax is calculated from plasma concentrations analyzed from blood samples collected between 0 and 48 hr.

  Up to Week 5

• Area Under the Curve From Time Zero to 24 Hours (AUC0_24)

  Area under the drug concentration-time curve from time zero to 24 hours postdose pk parameteres are calculated from plasma concentration analyzed from blood samples collected between 0 and 48 hr

  Up to Week 5

• Area Under the Curve From Time Zero to Infinity (AUC0_infinity)

  calculated by summing AUC0-last and the AUC extrapolated from tlast to infinity: AUC0-∞ = AUC0-last+ Clast / \| λz \| Clast / \| λz \| is the extrapolated area under the curve from tlast to infinity. If this quantity is greater than 20% of AUC0-∞, then AUC0-∞ was considered to be missing. Pk parameters are calculated from plasma concentration analyzed from blood samples collected between 0 and 48 hr.

  Up to Week 5

Secondary Outcomes (15)

• Clearance (CL) for IV Infusion of 50 mcg of Glycopyrrolate

  Up to Week 5

• Volume of Distribution During the Elimination Phase (Vz) for IV Infusion of 50 mcg of Glycopyrrolate

  Up to Week 5

• Time of Occurrence of Cmax (Tmax) for IV Infusion of 50 mcg of Glycopyrrolate

  Up to Week 5

• Terminal Half Life (t1/2) for IV Infusion of 50 mcg of Glycopyrrolate

  Up to Week 5

• Area Under the Curve Zero to 48 Hours (AUC0_48) for Seebri Breezhaler and Sun-101 AUC0-48, CL/F, Vz/F, Tmax, t½, and Dose Normalized Cmax, AUC0-24, AUC0-48, AUC0-∞ - AUC0-∞ -

  Up to Week 5

Study Arms (5)

SUN-101 via eFlow nebulizer

EXPERIMENTAL

50 mcg glycopyrrolate via Electronic Nebulizer

Drug: SUN-101 via eFlow nebulizer

SUN-101 via eFlow nebulizer with activated charcoal

EXPERIMENTAL

50 mcg glycopyrrolate via Electronic Nebulizer with activated charcoal

Drug: SUN-101 via eFlow nebulizer with activated charcoal

Seebri® Breezhaler®

ACTIVE COMPARATOR

63 mcg glycopyrronium bromide (50 mcg glycopyrronium) via DPI

Drug: Seebri® Breezhaler®

Seebri® Breezhaler® with activated charcoal

ACTIVE COMPARATOR

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

Drug: Seebri® Breezhaler® with activated charcoal

: Glycopyrrolate Injection

ACTIVE COMPARATOR

50 mcg glycopyrrolate via IV infusion

Drug: Glycopyrrolate Injection

Interventions

SUN-101 via eFlow nebulizer DRUG

50 mcg glycopyrrolate via Electronic Nebulizer

Also known as: Glycopyrrolate

SUN-101 via eFlow nebulizer

SUN-101 via eFlow nebulizer with activated charcoal DRUG

50 mcg glycopyrrolate via Electronic Nebulizer with activated charcoal

Also known as: Glycopyrrolate

SUN-101 via eFlow nebulizer with activated charcoal

Seebri® Breezhaler® DRUG

63 mcg glycopyrronium bromide (50 mcg glycopyrronium) via DPI

Also known as: glycopyrronium, glycopyrronium bromide

Seebri® Breezhaler®

Seebri® Breezhaler® with activated charcoal DRUG

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

Also known as: glycopyrronium, glycopyrronium bromide

Seebri® Breezhaler® with activated charcoal

Glycopyrrolate Injection DRUG

50 mcg glycopyrrolate via IV

Also known as: Glycopyrrolate

: Glycopyrrolate Injection

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 40 to 70 years-old, inclusive.
• A clinical diagnosis of moderate to severe COPD according to the GOLD 2014 guidelines.
• Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, or equivalent).
• Post-bronchodilator (following inhalation of ipratropium bromide) FEV1 ≥ 30% and ≤ 80% of predicted normal during the Screening Period.
• Post-bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio ≤ 0.70 during the Screening Period.
• Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and/or European Respiratory Society (ERS) guidelines (2005).
• 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.
• Willing and able to remain at the study site for at least 24 hours for each treatment day.
• Willing and able to provide written informed consent.
• Willing and able to attend all study visits and adhere to all study assessments and procedures.

You may not qualify if:

• 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.
• Current evidence or history of a clinically significant abnormality of cardiac rhythm and/or conduction findings.
• Concomitant clinically significant respiratory disease other than COPD (eg, asthma, tuberculosis, bronchiectasis, or other non-specific pulmonary disease).
• 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.
• Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to the Screening Period.
• Use of daily oxygen therapy \> 10 hours per day.
• Use of oral, intravenous, or intramuscular steroids within 3 months prior to the Screening Period.
• Respiratory tract infection within 6 weeks prior to or during the Screening Period.
• 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.
• History of or clinically significant ongoing bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within the previous 6 months.
• History of narrow-angle glaucoma.
• Prolonged QTc interval (\> 450 msec for males and \> 470 msec for females) during the Screening Period, or history of long QT syndrome.

Sponsors & Collaborators

• Sunovion Respiratory Development Inc.: lead

Study Sites (2)

Queen Anne Street Medical Center

London, W1G 8HU, United Kingdom

Location

Medicines evaluation Unit Ltd.

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (1)

• Leaker BR, Singh D, Nicholson GC, Hezelova B, Goodin T, Ozol-Godfrey A, Galluppi G, Barnes PJ. Evaluation of systemic absorption and bronchodilator effect of glycopyrronium bromide delivered by nebulizer or a dry powder inhaler in subjects with chronic obstructive pulmonary disease. Respir Res. 2019 Jun 28;20(1):132. doi: 10.1186/s12931-019-1113-z.

  PMID: 31253162 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Glycopyrrolate; Charcoal

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbon; Elements; Inorganic Chemicals

Results Point of Contact

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

1-866-503-6351

Study Officials

• Head of Global Clinical, Respiratory and Bio-threapeutics

  Sunovion Pharmaceuticals

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2015
• First Posted: July 30, 2015
• Study Start: October 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: October 25, 2018
• Results First Posted: September 14, 2018

Record last verified: 2018-09

Locations

GB (2)