A Study of the Efficacy and Safety of NVA237 in Patients With Moderate to Severe COPD

NCT02371629 | Completed Phase 4 Results

• 1 other identifier: CNVA237A2320
• Study Type: interventional
• Target: 776
• Locations: 10 countries
• Sites: 81

Brief Summary

This study is a post-authorization commitment to the European Medicines Agency (EMA). The study serves to determine whether the treatment of patients with stable, symptomatic Chronic Obstructive Pulmonary Disease (COPD) with the investigational drug NVA237 is efficient and safe. The efficacy and safety of the drug was tested for twice daily dosing against once daily dosing.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Anticholinergic; Antimuscarinic; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease; Chronic Obstructive Pulmonary Disease; COPD; LAMA; Lung Disease; Lung Diseases, Obstructive; Lung Function; Muscarinic receptor antagonist; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12

  Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FEV1 defined as the mean of two measurements at 23 hours 15 minutes and 23 hour 45 minutes post dosing. Baseline FEV1 was defined as the average of the -45 minutes and -15 minutes FEV1 values taken on Day 1. An analysis-of-covariance (ANCOVA) for repeated measurements, also known as mixed model for repeated measures (MMRM), was performed for the change from baseline of trough FEV1 at Week 12. The model included treatment, COPD severity, baseline smoking status, baseline ICS use, region, and visit (Day 1, and Weeks 12 and 26) as factors and baseline FEV1 as a covariate.

  Baseline, Week 12

Secondary Outcomes (14)

• Change From Baseline in Area Under The Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) for Different Time Spans Post Dosing at Week 12

  Baseline, 0-12 hour, 0-24 hour , 12-24 hour post dose at Week 12

• Change From Baseline in Area Under The Curve (AUC 0-12 Hour) for Forced Expiratory Volume in One Second (FEV1) Post Dosing at Day 1

  Baseline, 0-12 hour post dose at Day 1

• Change From Baseline in Area Under The Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) for Different Time Spans Post Dosing at Week 26

  Baseline, 0-12 hour, 0-24 hour , 12-24 hour post dose at Week 26

• Change From Baseline in Total St. George's Respiratory Questionnaire (SGRQ) Score at Week 12 and Week 26

  Baseline, 12 Weeks, 26 Weeks

• Percentage of Patients With a Clinically Significant Improvement in St George Respiratory Questionnaire at Week 12 and Week 26

  Baseline, 12 Weeks, 26 Weeks

Study Arms (2)

NVA237 Twice daily

EXPERIMENTAL

Patients randomized to this arm received an NVA237 22 μg capsule in the morning and evening for 26 weeks. All participants received salbutamol as rescue medicine.

Drug: NVA237; Drug: Salbutamol

NVA237 Once daily

EXPERIMENTAL

Patients randomized to this arm received an NVA237 44 μg capsule in the morning and a placebo capsule in the evening for 26 weeks. All participants received salbutamol as rescue medicine.

Drug: NVA237; Drug: Placebo; Drug: Salbutamol

Interventions

NVA237 DRUG

NVA237 capsules for inhalation, delivered via a Single Dose Dry Powder Inhaler (SDDPI) called Concept1

Also known as: glycopyrronioum bromide

NVA237 Once daily; NVA237 Twice daily

Placebo DRUG

Placebo to NVA237

NVA237 Once daily

Salbutamol DRUG

All patients received salbutamol (100 μg) as only rescue medication

NVA237 Once daily; NVA237 Twice daily

Eligibility Criteria

• Age: 41 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed
• Male and female adults aged ≥40 years
• Patients with stable COPD according to the current GOLD strategy (GOLD 2014)
• Current or ex-smokers who have a smoking history of at least 10 pack years- an ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at screening
• mMRC grade of at least 2 at Visit 101
• Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30 % and \< 80 % of the predicted normal, and a post-bronchodilator FEV1/FVC \< 0.70 at Visit 101.

You may not qualify if:

• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test; Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment
• Patients with Type I or uncontrolled Type II diabetes; Patients with a history of long QT syndrome or whose QTc measured at run-in (Fridericia method) is prolonged (\>450 ms for males and \>460 for females) and confirmed by a central assessor
• Patients requiring long term oxygen therapy prescribed for \>12 h per day; Patients with any history of asthma.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (81)

Novartis Investigative Site

Genk, Limburg, 3600, Belgium

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Jambes, Namur, 5100, Belgium

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Sevlievo, Gabrovo, 5400, Bulgaria

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Sofia, Sofia-Grad, 1336, Bulgaria

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Gabrovo, 5300, Bulgaria

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Kozloduy, 3320, Bulgaria

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Lom, 3600, Bulgaria

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Lovech, 5500, Bulgaria

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Montana, 3400, Bulgaria

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Razgrad, 7200, Bulgaria

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Roman, 3130, Bulgaria

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Rousse, 7000, Bulgaria

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Silistra, 7500, Bulgaria

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Sliven, 8800, Bulgaria

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Smolyan, 4700, Bulgaria

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Sofia, 1202, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1431, Bulgaria

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Troyan Municipality, 5600, Bulgaria

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Veliko Tarnovo, 5000, Bulgaria

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Vidin, 3700, Bulgaria

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Turku, FIN-20100, Finland

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Heidelberg, Baden-Wurttemberg, 69126, Germany

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Hanover, Lower Saxony, 30159, Germany

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Hanover, Lower Saxony, 30167, Germany

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Koblenz, Rhineland-Palatinate, 56068, Germany

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Großhansdorf, Schleswig-Holstein, 22927, Germany

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Berlin, 10117, Germany

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Dresden, 01069, Germany

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Frankfurt, 60596, Germany

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Greifswald, 17475, Germany

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Lübeck, 23552, Germany

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Schwerin, 19055, Germany

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Wiesbaden, 65187, Germany

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Balassagyarmat, 2660, Hungary

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Debrecen, 4032, Hungary

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Farkasgyepű, 8582, Hungary

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Pécs, 7635, Hungary

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Sopron, H-9400, Hungary

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Szarvas, 5540, Hungary

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Szeged, 6722, Hungary

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Rehovot, 7610001, Israel

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Tarnów, Lesser Poland Voivodeship, 33-100, Poland

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Wroclaw, Lower Silesian Voivodeship, 53-301, Poland

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Lodz, Lódzkie, 90-153, Poland

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Chorzów, Silesian Voivodeship, 41-500, Poland

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Bialystok, 15-044, Poland

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Gdansk, 80 952, Poland

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Kielce, 25-751, Poland

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Lodz, 90-141, Poland

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Sopot, 81-741, Poland

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Wilkowice, 43-365, Poland

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Craiova, Dolj, 200515, Romania

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Constanța, Jud. Constanta, 900002, Romania

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Tg Mures, Mureș County, 540136, Romania

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Timișoara, Timiș County, 300310, Romania

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Baia Mare, Romania

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Bucharest, 030317, Romania

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Bucharest, 050159, Romania

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Cluj-Napoca, 400162, Romania

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Cluj-Napoca, 400371, Romania

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Kazan', Tatarstan Republic, 420015, Russia

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Chelyabinsk, 454021, Russia

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Izhevsk, 426061, Russia

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Kemerovo, 650002, Russia

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Kemerovo, 650099, Russia

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N.Novgorod, 603126, Russia

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Nizhny Novgorod, 603011, Russia

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Ryazan, 390039, Russia

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Saint Petersburg, 194325, Russia

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Saint Petersburg, 197022, Russia

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Sestroretsk, 197706, Russia

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Smolensk, 214019, Russia

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Yaroslavl, 150000, Russia

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Yaroslavl, 150003, Russia

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Yaroslavl, 150062, Russia

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Malmo, Skåne County, 21152, Sweden

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Lidingo, Södermanland County, 18158, Sweden

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Novartis Investigative Site

Gothenburg, Västra Götaland County, SE-413 45, Sweden

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Novartis Investigative Site

Lund, SE-221 85, Sweden

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Novartis Investigative Site

Linköping, Östergötland County, 587 58, Sweden

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MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Lung Diseases; Lung Diseases, Obstructive; Respiratory Tract Diseases

Interventions

Glycopyrrolate; Albuterol

Condition Hierarchy (Ancestors)

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; Ethanolamines; Amino Alcohols; Alcohols; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2015
• First Posted: February 25, 2015
• Study Start: June 24, 2015
• Primary Completion: November 16, 2016
• Study Completion: November 16, 2016
• Last Updated: August 9, 2019
• Results First Posted: August 9, 2019

Record last verified: 2019-06

Locations

RU (15); IL (1); BU (19); FI (1); BE (2); DE (12); RO (9); PL (10); SE (5); HU (7)