Safety and Efficacy Study of Glyco pMDI After Single and Repeated Administration (GLY2)

Randomized, Double-blind, Placebo-controlled, Cross-over Study to Investigate the Bronchodilator Efficacy and Safety After Single and Repeated Administrations of Different Doses of Glycopyrrolate Via pMDI in Moderate to Severe COPD Patients.

The purpose of this study is to evaluate the safety and the efficacy of Glycopyrrolate as pMDI after single and repeated administration.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Glycopyrrolate; Drug: placebo; Drug: Tiotropium

Detailed Description

The study is divided into two parts:

- Part 1 will be conducted according to a single-centre, randomized, double-blind, placebo-controlled, single-dose escalation, alternating crossover design in two groups of COPD patients.

Treatments to be administered on Part 1 (SD1, SD2, SD3, SD4, SD5, SP). The primary objective of Part 1 is the evaluation of the safety and tolerability of Glyco after single administration.

- Part 2 will be conducted according to a single-centre, randomized, double-blind, placebo-controlled, 4-period, 4-treatment, repeated dose cross-over design followed by an open-label extension period with tiotropium.

Treatments administered on Part 2 (MD1, MD2, MD3, MP, Tiotropium). On the last treatment day in the morning, Formoterol 12 µg will be administered to all patients on top of placebo or Glyco or Tiotropium.

The primary objective of Part 2 is the evaluation of the efficacy of Glyco after repeated administration.

Part 2 will start after a safety review of the results obtained from Part 1.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
    • Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females patients aged 40-75 years;
• Written informed consent obtained;
• Diagnosis of moderate-severe COPD, according to the GOLD guidelines;
• Current or ex-smokers with a smoking history of ≥ 10 pack-years
• Post bronchodilator FEV1 between 40% and 80% predicted values (40% ≤ FEV1 < 80%), documented at screening visit ;
• Post bronchodilator FEV1/Forced Vital Capacity (FEV1/FVC) ≤ 0.70 (absolute value) documented at screening visit;
• Airway reversibility of at least 100 mL within 30 to 45 minutes after inhalation of ipratropium 80µg.

Exclusion Criteria:

• History of chronic or seasonal allergy
• Blood eosinophil count above 600 per µl
• Clinically relevant findings on physical examination laboratory and ECG parameters at screening
• Occurrence of clinically relevant abnormalities in the 24-h Holter ECG recording at screening;
• Significant disease not related to COPD (eg. Myocardial infarction, stroke within the preceding 6 months);
• Respiratory tract infection (including upper tract) 4 weeks prior to study entry requiring changing treatment;
• Patients requiring oxygen therapy on a daily basis for chronic hypoxemia;
• History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which is considered to be clinically significant by the investigator.
• Intolerance/hypersensitivity or any contra-indication to treatment with M3 Antagonist or any of the excipients contained in the formulations used in the study.
• History of alcohol or substance abuse that in the opinion of the Investigator may be of clinical significance.
• Patients treated with slow-release oral or parental corticosteroids 8 weeks prior to Screening Visit.
• Patients treated with tiotropium in the 10 days prior to the Screening Visit;
• Pregnant or lactating women and female or male subjects not willing to use an acceptable method of contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Glyco SD1; Single administration of Glyco pMDI dose level 1	Drug: Glycopyrrolate; pressurized metered dose inhaler; Other Names: CHF 5259
EXPERIMENTAL: Glyco SD2; Single administration of Glyco pMDI dose level 2	Drug: Glycopyrrolate; pressurized metered dose inhaler; Other Names: CHF 5259
EXPERIMENTAL: Glyco SD3; Single administration of Glyco pMDI dose level 3	Drug: Glycopyrrolate; pressurized metered dose inhaler; Other Names: CHF 5259
EXPERIMENTAL: Glyco SD4; Single administration of Glyco pMDI dose level 4	Drug: Glycopyrrolate; pressurized metered dose inhaler; Other Names: CHF 5259
EXPERIMENTAL: Glyco SD5; Single administration of Glyco pMDI dose level 5	Drug: Glycopyrrolate; pressurized metered dose inhaler; Other Names: CHF 5259
PLACEBO_COMPARATOR: Placebo SP; Single administration of Placebo pMDI	Drug: placebo; pressurized metered dose inhaler
EXPERIMENTAL: Glyco MD1; Multiple administration of Glyco pMDI dose level 1	Drug: Glycopyrrolate; pressurized metered dose inhaler; Other Names: CHF 5259
EXPERIMENTAL: Glyco MD2; Multiple administration of Glyco pMDI dose level 2	Drug: Glycopyrrolate; pressurized metered dose inhaler; Other Names: CHF 5259
EXPERIMENTAL: Glyco MD3; Multiple administration of Glyco pMDI dose level 3	Drug: Glycopyrrolate; pressurized metered dose inhaler; Other Names: CHF 5259
PLACEBO_COMPARATOR: Placebo MP; Multiple administration of placebo pMDI	Drug: placebo; pressurized metered dose inhaler
ACTIVE_COMPARATOR: Tiotropium; Multiple administration of tiotropium	Drug: Tiotropium; inhalation powder, hard capsule; Other Names: Spiriva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Adverse events, vital signs, ECG parameters, 24-hours ECG holter recording, clinical laboratory abnormalities. This primary outcome is for the Part 1 of the study.	Up to 24 hours after single administration
Lung function (trough FEV1)	This primary variable is for the Part 2 of the study.	12 hours post dose after repeated administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung function	for Part 1 of the study	up to 24 hours post dose
Lung function (other parameters)	for Part 2 of the study	up to 12 hours after repated administration
Body plethysmography	for Part 2 of the study	up tp 12 hours after repeated administration
Pharmacokinetics	Pharmacokinetics in plasma and urine. For Part 2 of the study.	up to 12 hours after single and repeated administration
Safety	Adverse events, Vital signs, ECG parameters, 24-hour ECG holter recording. For Part 2 of the study.	up to 12 hours after single and repeated administration

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.

Publications and helpful links

General Publications

• Singh D, Scuri M, Collarini S, Vezzoli S, Mariotti F, Muraro A, Acerbi D. Bronchodilator efficacy of extrafine glycopyrronium bromide: the Glyco 2 study. Int J Chron Obstruct Pulmon Dis. 2017 Jul 7;12:2001-2014. doi: 10.2147/COPD.S137659. eCollection 2017.

Helpful Links

• Study Record on EU Clinical Trials Register including results
• CSR Synopsis available in the CHIESI Clinical Study Register

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: August 5, 2010
• First Submitted That Met QC Criteria: August 5, 2010
• First Posted (ESTIMATE): August 6, 2010

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Glycopyrrolate; Tiotropium Bromide
• Other Study ID Numbers: CCD-0916-PR-0032; 2010-018668-18 (EUDRACT_NUMBER)