Efficacy of NVA237 Compared to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD) (FAST)

A Randomized, Double-blind, Multicenter, 2-period Single-dose Cross-over Study to Assess the Early Bronchodilation of Glycopyrronium Bromide (44 μg o.d.) Compared to Tiotropium (18 µg. o.d.) in Patients With Moderate to Severe COPD (FAST Study)

The purpose of this study is to further figure out differences of glycopyrronium bromide compared to tiotropium in early bronchodilation measured by a comprehensive assessment of lung function that includes hyperinflation and specific airway resistance in patients with moderate to severe COPD.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: NVA237; Drug: Tiotropium; Drug: Placebo to tiotropium; Drug: Salbutamol; Drug: Placebo to NVA237

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12043
    • Novartis Investigative Site
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Berlin, Germany, 12687
    • Novartis Investigative Site
  • Berlin, Germany, 13086
    • Novartis Investigative Site
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
  • Gelsenkirchen, Germany, 45879
    • Novartis Investigative Site
  • Grosshansdorf, Germany, 22947
    • Novartis Investigative Site
  • Gummersbach, Germany, 51643
    • Novartis Investigative Site
  • Hamburg, Germany, 20354
    • Novartis Investigative Site
  • Kassel, Germany, 34121
    • Novartis Investigative Site
  • Leipzig, Germany, 04207
    • Novartis Investigative Site
  • Lübeck, Germany, 23552
    • Novartis Investigative Site
  • Rüdersdorf, Germany, 15562
    • Novartis Investigative Site
  • Sonneberg, Germany, 96515
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female adults aged ≥40 years
• Patients with moderate to severe COPD defined by a post-bronchodilator Forced Expiratory Volume in One Second (FEV1)/(FVC) Forced Vital Capacity ratio of <0.70 and a post-bronchodilator FEV1 of ≤70% and FEV1 ≥ 30% of predicted normal values.
• Current or ex-smokers who have a smoking history of at least 10 pack years.

Exclusion Criteria:

• Pregnant or nursing (lactating) women
• Patients who have a clinically significant laboratory abnormality at run-in
• Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment (GFR <50 ml/min/1,732) or urinary retention. (BPH patients who are stable on treatment can be considered).
• Patients with any history of asthma
• Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation
• Patients receiving medications in the classes listed in the protocol as prohibited.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NVA237 followed by tiotropium; Period 1: NVA237 plus placebo to tiotropium on day 1, followed by a 7 day washout. Period 2: tiotropium plus placebo to NVA237 on day 8. Salbutamol was used as rescue medication.	Drug: NVA237; NVA237 44 µg inhalation capsules once daily, delivered via single-dose dry-powder inhaler (SDDPI); Drug: Tiotropium; Tiotropium 18 μg once daily delivered via HandiHaler® device.; Drug: Placebo to tiotropium; Placebo to tiotropium once daily delivered via HandiHaler® device; Drug: Salbutamol; Used as resuce medication
Experimental: Tiotropium followed by NVA237; Period 1: tiotropium plus placebo to NVA237 on day 1, followed by a 7 day washout. Period 2: NVA237 plus placebo to tiotropium on day 8. Salbutamol was used as rescue medication.	Drug: Salbutamol; Used as resuce medication; Drug: Placebo to NVA237; Placebo to NVA237 once daily, delivered via single-dose dry-powder inhaler (SDDPI).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in One Second (FEV1) Area Under Curve (AUC) 0-2	Standardized Forced Expiratory Volume in One Second (FEV1) AUC0-2h will be measured via spirometry. The AUC will be calculated from the FEV1 measurements obtained at timepoints between 0 min and 2h using the trapezoidal rule and will be standardized (=divided) by the measurement time (i.e. 2h).	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in One Second (FEV1) 15 Min Post Dose	Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 will be measured by spirometry. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability.	Day 1
Specific Airway Resistance (sRAW)	Specific Airway Resistance (sRAW) indicates volume and resistance-dependent work of breathing needed in order to generate a reference flow rate of 1 L/s, measured by kPa*s. Whole body plethysmography (Bodybox) is used to measure SRaw.	Day 1
Functional Resistance Capacity (FRCpleth)	Functional Resistance Capacity (FRCpleth) will be measured using whole body plethysmography (Bodybox).	Day 1
Residual Volume (RV)	Residual Volume (RV) will be measured using whole body plethysmography (Bodybox).	Day 1
Total Lung Capacity (TLC)	Total Lung Capacity (TLC) is the best vital capacity plus residual volume (RV). Whole body plethysmography (Bodybox) will be used to measure TLC.	Day 1
Inspiratory Capacity (IC)	Inspiratory Capacity (IC) is the volume of air breathed in by a maximum inspiration at the end of a normal expiration. Whole body plethysmography (Bodybox) will be used to measure IC.	Day 1

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Watz H, Mailander C, May C, Baier M, Kirsten AM. Fast onset of action of glycopyrronium compared with tiotropium in patients with moderate to severe COPD - A randomised, multicentre, crossover trial. Pulm Pharmacol Ther. 2017 Feb;42:13-20. doi: 10.1016/j.pupt.2016.12.001. Epub 2016 Dec 9.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: August 9, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (Estimate): August 14, 2013

Study Record Updates

• Last Update Posted (Estimate): January 1, 2015
• Last Update Submitted That Met QC Criteria: December 19, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Glycopyrrolate; Tiotropium Bromide
• Other Study ID Numbers: CNVA237ADE02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No