Clinical trial NCT01176903: Safety and Efficacy Study of Glyco pMDI After Single and Repeated Administration
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2010-08-06
Enrollment: 65
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety
timeFrame: Up to 24 hours after single administration
measure: Lung function (trough FEV1)
timeFrame: 12 hours post dose after repeated administration
Secondary outcomes:
measure: Lung function
timeFrame: up to 24 hours post dose
measure: Lung function (other parameters)
timeFrame: up to 12 hours after repated administration
measure: Body plethysmography
timeFrame: up tp 12 hours after repeated administration
measure: Pharmacokinetics
timeFrame: up to 12 hours after single and repeated administration
measure: Safety
timeFrame: up to 12 hours after single and repeated administration
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
affiliation: Medicines Evaluation Unit Ltd
name: Dave Singh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.