Safety and Efficacy Study of Glyco pMDI After Single and Repeated Administration
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)
- Interventions
- Registration Number
- NCT01176903
- Lead Sponsor
- Chiesi Farmaceutici S.p.A.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 65
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo SP placebo Single administration of Placebo pMDI Placebo MP placebo Multiple administration of placebo pMDI Glyco SD1 Glycopyrrolate Single administration of Glyco pMDI dose level 1 Glyco SD3 Glycopyrrolate Single administration of Glyco pMDI dose level 3 Glyco SD2 Glycopyrrolate Single administration of Glyco pMDI dose level 2 Glyco SD4 Glycopyrrolate Single administration of Glyco pMDI dose level 4 Glyco SD5 Glycopyrrolate Single administration of Glyco pMDI dose level 5 Glyco MD1 Glycopyrrolate Multiple administration of Glyco pMDI dose level 1 Glyco MD3 Glycopyrrolate Multiple administration of Glyco pMDI dose level 3 Glyco MD2 Glycopyrrolate Multiple administration of Glyco pMDI dose level 2 Tiotropium Tiotropium Multiple administration of tiotropium
- Primary Outcome Measures
Name Time Method Safety Up to 24 hours after single administration 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.Lung function (trough FEV1) 12 hours post dose after repeated administration This primary variable is for the Part 2 of the study.
- Secondary Outcome Measures
Name Time Method Lung function up to 24 hours post dose for Part 1 of the study
Lung function (other parameters) up to 12 hours after repated administration for Part 2 of the study
Body plethysmography up tp 12 hours after repeated administration for Part 2 of the study
Pharmacokinetics up to 12 hours after single and repeated administration Pharmacokinetics in plasma and urine. For Part 2 of the study.
Safety up to 12 hours after single and repeated administration Adverse events, Vital signs, ECG parameters, 24-hour ECG holter recording. For Part 2 of the study.
Trial Locations
- Locations (1)
Medicines Evaluation Unit
🇬🇧Manchester, United Kingdom