Effect of Glycopyrronium on Morning Symptoms and Pulmonary Function in Patients With Moderate to Severe COPD

NCT01959516 | Completed Phase 4 Results

• 1 other identifier: CNVA237A3401
• Study Type: interventional
• Target: 124
• Locations: 4 countries
• Sites: 21

Brief Summary

This study purpose is to further study the profiles of glycopyrronium (NVA237) and tiotropium during the first hours after dosing and their impact on pulmonary function, COPD symptoms and ability to perform daily activities by the patient.

Conditions

COPD

Keywords

COPD, early morning symptoms

Outcome Measures

Primary Outcomes (1)

• Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment.

  Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) will measured via spirometry and calculated from 0 to 4 hours post-dose on day 1 of study treatment.

  Day 1

Secondary Outcomes (1)

• Comparison of Glycopyrronium QD Versus Tiotropium QD on Symptoms Outcome

  day 1 (baseline) and week 4

Study Arms (2)

Sequence A ⇒ B

EXPERIMENTAL

Participants will receive sequence A = glycopyrronium + placebo to tiotropium during 28 days, followed by a 14 day washout period, then sequence B= tiotropium + placebo to glycopyrronium for 28 days.

Drug: Glycopyrronium; Drug: Tiotropium; Drug: Placebo to glycopyrronium; Drug: Placebo to tiotropium

Sequence B ⇒ A

EXPERIMENTAL

Participants will receive sequence B= tiotropium + placebo to glycopyrronium during 28 days, followed by a 14 day washout period, then sequence A= glycopyrronium + placebo to tiotropium for 28 days.

Drug: Glycopyrronium; Drug: Tiotropium; Drug: Placebo to glycopyrronium; Drug: Placebo to tiotropium

Interventions

Glycopyrronium DRUG

Glycopyrronium capsule for inhalation once per day via SDDPI

Sequence A ⇒ B; Sequence B ⇒ A

Tiotropium DRUG

Tiotropium capsule for inhalation once per day via HandiHaler® device

Sequence A ⇒ B; Sequence B ⇒ A

Placebo to glycopyrronium DRUG

Placebo to glycopyrronium capsule for inhalation once per day via SDDPI

Sequence A ⇒ B; Sequence B ⇒ A

Placebo to tiotropium DRUG

Placebo to tiotropium capsule for inhalation once per day via HandiHaler® device

Sequence A ⇒ B; Sequence B ⇒ A

Eligibility Criteria

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

You may qualify if:

• Male and female adults aged ≥ 40 years.
• Co-operative outpatients with a clinical diagnosis of moderate to severe COPD confirmed by spirometry according to GOLD criteria 2013 and including all of the following: a) Current or ex-smokers who have a smoking history of at least 10 pack years (e.g.10 pack years = 1 pack /day x 10 years or ½ pack/day x 20 years). An ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at Screening. b) Patients with airflow limitation indicated by a post-bronchodilator FEV1 \< 80% and ≥ 40% of the predicted normal value at Visit 2 (Post- bronchodilator refers to within 10-15 min of inhalation of 400 µg (4x100 µg) of salbutamol). c) .Post-bronchodilator FEV1/FVC \< 0.7 at Visit 2 (Post- bronchodilator refers to within 10-15 min of inhalation of 400 µg (4x100 µg) of salbutamol).
• Patients with a COPD Assessment Test (CAT) score ≥ 10 at Visit 2.

You may not qualify if:

• Patients on any long-acting bronchodilator therapy. Those patients may enter the study after bronchodilator withdrawal during a 10-day wash-out period (only rescue salbutamol allowed as bronchodilator therapy during wash-out). Patients on fixed combination of long acting β2-agonists/inhaled corticosteroid (LABA/ICS) therapy before screening must be switched to the equivalent dose of ICS monotherapy and salbutamol as rescue.
• Patients receiving any other prohibited COPD-related medications specified in Table 5-1 must undergo the required wash-out period prior to Visit 2.
• Patients who have had a clinical history of asthma.
• Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis or clinically significant bronchiectasis.
• Patients with alpha-1-antitrypsin deficiency.
• Patients with contraindications for LAMA treatment including medical history of symptomatic prostatic hypertrophy, bladder neck obstruction, narrow-angle glaucoma and severe renal impairment (estimated glomerular filtration rate below 30 ml/min/1.73 m2) documented in the previous 6 months.
• Patients with a history of unstable cardiovascular disease or arrhythmias including atrial fibrillation/flutter or long QT syndrome or whose resting QTcF (calculated according to Fridericia QT correction formula preferred, but Bazett acceptable) is prolonged (≥ 450 msec for males and ≥ 460 msec for females) at screening (Visit 1) or baseline (Visit 2, baseline 1).
• Concomitant use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study.
• Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof: -anticholinergic agents - long and short acting 2 agonists -sympathomimetic amines -excipients of the trial medication (lactose monohydrate and/or magnesium estearate)
• Patients whose body mass index (BMI) is less than 15 or greater than 40 kg/m2.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

Novartis Investigative Site

Berlin, Germany, 12099, Germany

Location

Novartis Investigative Site

Potsdam, Germany, 14467, Germany

Location

Novartis Investigative Site

Wiesbaden, Germany, 65187, Germany

Location

Novartis Investigative Site

Geesthacht, Schleswig-Holstein, 12502, Germany

Location

Novartis Investigative Site

Berlin, State of Berlin, 10119, Germany

Location

Novartis Investigative Site

Berlin, 13156, Germany

Location

Novartis Investigative Site

Halle, 06108, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Leipzig, 04275, Germany

Location

Novartis Investigative Site

Florence, FI, 50122, Italy

Location

Novartis Investigative Site

Milan, MI, 20138, Italy

Location

Novartis Investigative Site

Orbassano, TO, 10043, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08026, Spain

Location

Novartis Investigative Site

Lugo, Galicia, 27003, Spain

Location

Novartis Investigative Site

Zaragoza, Zaragoza, 50009, Spain

Location

Novartis Investigative Site

Cambridge, United KIngdom, CB7 5JD, United Kingdom

Location

Novartis Investigative Site

Watford, United Kingdom, WD25 7NL, United Kingdom

Location

Novartis Investigative Site

Blackpool, FY3 7EN, United Kingdom

Location

Novartis Investigative Site

Bradford, BD9 6RJ, United Kingdom

Location

Novartis Investigative Site

Cardiff, CF5 4AD, United Kingdom

Location

Novartis Investigative Site

Wishaw, ML2 0DP, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Glycopyrrolate; Tiotropium Bromide

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; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2013
• First Posted: October 10, 2013
• Study Start: February 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: April 15, 2016
• Results First Posted: April 15, 2016

Record last verified: 2016-03

Locations

DE (9); GB (6); ES (3); IT (3)