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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Randomized, Double-blind, Parallel Group, 26-week Study Evaluating the Efficacy, Safety and Tolerability of NVA237 Given Once or Twice Daily, in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02371629
• Other study ID #: CNVA237A2320
• Status: Completed
• Phase: Phase 4
• Start date: June 24, 2015
• Est. completion date: November 16, 2016

Study information

• Verified date: June 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 776
• Est. completion date: November 16, 2016
• Est. primary completion date: November 16, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 41 Years to 84 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• NVA237
NVA237 capsules for inhalation, delivered via a Single Dose Dry Powder Inhaler (SDDPI) called Concept1
• Placebo
Placebo to NVA237
• Salbutamol
All patients received salbutamol (100 µg) as only rescue medication

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Genk	Limburg
Belgium	Novartis Investigative Site	Jambes	Namur
Bulgaria	Novartis Investigative Site	Gabrovo
Bulgaria	Novartis Investigative Site	Kozloduj
Bulgaria	Novartis Investigative Site	Lom
Bulgaria	Novartis Investigative Site	Lovech
Bulgaria	Novartis Investigative Site	Montana
Bulgaria	Novartis Investigative Site	Razgrad
Bulgaria	Novartis Investigative Site	Roman
Bulgaria	Novartis Investigative Site	Ruse
Bulgaria	Novartis Investigative Site	Sevlievo	Gabrovo
Bulgaria	Novartis Investigative Site	Silistra
Bulgaria	Novartis Investigative Site	Sliven
Bulgaria	Novartis Investigative Site	Smolyan
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia	Sofia-Grad
Bulgaria	Novartis Investigative Site	Troyan
Bulgaria	Novartis Investigative Site	Veliko Tarnovo
Bulgaria	Novartis Investigative Site	Vidin
Finland	Novartis Investigative Site	Turku
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Großhansdorf	Schleswig-Holstein
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Heidelberg	Baden-Württemberg
Germany	Novartis Investigative Site	Koblenz	Rheinland-Pfalz
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Schwerin
Germany	Novartis Investigative Site	Wiesbaden
Hungary	Novartis Investigative Site	Balassagyarmat
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Farkasgyepu
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Sopron
Hungary	Novartis Investigative Site	Szarvas
Hungary	Novartis Investigative Site	Szeged
Israel	Novartis Investigative Site	Rehovot
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Chorzow	Slaskie
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Kielce
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lodz	Lódzkie
Poland	Novartis Investigative Site	Sopot
Poland	Novartis Investigative Site	Tarnow	Malopolskie
Poland	Novartis Investigative Site	Wilkowice
Poland	Novartis Investigative Site	Wroclaw	Dolnoslaskie
Romania	Novartis Investigative Site	Baia Mare
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Cluj-Napoca
Romania	Novartis Investigative Site	Constanta	Jud. Constanta
Romania	Novartis Investigative Site	Craiova	Dolj
Romania	Novartis Investigative Site	Tg Mures	Mures
Romania	Novartis Investigative Site	Timisoara	Timis
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Izhevsk
Russian Federation	Novartis Investigative Site	Kazan	Tatarstan Republic
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	N.Novgorod
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	Sestroretsk
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	Yaroslavl
Russian Federation	Novartis Investigative Site	Yaroslavl
Russian Federation	Novartis Investigative Site	Yaroslavl
Sweden	Novartis Investigative Site	Göteborg	Vastra Gotalands Lan
Sweden	Novartis Investigative Site	Lidingo	Sodermanlands Lan
Sweden	Novartis Investigative Site	Linkoping	Ostergotlands Lan
Sweden	Novartis Investigative Site	Lund
Sweden	Novartis Investigative Site	Malmo	Skane Lan

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Finland,  Germany,  Hungary,  Israel,  Poland,  Romania,  Russian Federation,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans (0-12h, 0-24h, 12-24h) within the overall serial measurement post dosing at week 12 of treatment. Baseline FEV1 was defined as the average of the -45 minutes and -15 minutes FEV1 values taken on Day 1.	Baseline, 0-12 hour, 0-24 hour , 12-24 hour post dose at Week 12
Secondary	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	The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for 0-12 hour, post dosing at Day 1 of treatment. Baseline FEV1 was defined as the average of the -45 minutes and -15 minutes FEV1 values taken on Day 1.	Baseline, 0-12 hour post dose at Day 1
Secondary	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	The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans (0-12h, 0-24h, 12-24h) within the overall serial measurement post dosing at week 26 of treatment. Baseline FEV1 was defined as the average of the -45 minutes and -15 minutes FEV1 values taken on Day 1.	Baseline, 0-12 hour, 0-24 hour , 12-24 hour post dose at Week 26
Secondary	Change From Baseline in Total St. George's Respiratory Questionnaire (SGRQ) Score at Week 12 and Week 26	The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that caused or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease.; A score was calculated for each of these three subscales and the total score was calculated. In each case, the lowest possible value was 0 and the highest 100. Higher values corresponded to greater impairment of health status.	Baseline, 12 Weeks, 26 Weeks
Secondary	Percentage of Patients With a Clinically Significant Improvement in St George Respiratory Questionnaire at Week 12 and Week 26	The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ).; The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that caused or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease.; A score was calculated for each of these three subscales and the total score was calculated. In each case, the lowest possible value was 0 and the highest 100.; A clinically significant improvement is defined as = 4 unit improvement from baseline score (a decrease of = 4).	Baseline, 12 Weeks, 26 Weeks
Secondary	Change From Baseline in Transitional Dyspnea Index (TDI) Focal Score at Week 12 and Week 26	Breathlessness at Week 12 and Week 26 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI) focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.	Baseline, 12 Weeks, 26 Weeks
Secondary	Percentage of Patients With a Clinically Important Improvement on Transitional Dyspnea Index (TDI) Focal Score at Week 12 and Week 26	Breathlessness at Week 12 and Week 26 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI) focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.; Clinically important improvement indicates = 1 unit in the TDI focal score at Weeks 12 and 26 in comparison to BDI focal score (an increase of = 1).	Baseline, 12 Weeks, 26 Weeks
Secondary	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Week 26	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. 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, Day 1, Week 26
Secondary	Change From Baseline in Forced Vital Capacity (FVC) at Individual Timepoints at Week 26	Mixed model for repeated measures was used to analyze change from baseline in FVC. Baseline FVC is defined as the average of the -45 min and -15 min FVC values taken on Day 1 prior to first dose.	Baseline, Week 26 (Day 183-184)
Secondary	Change From Baseline in Inspiratory Capacity (IC) at Individual Timepoints at Week 26	Mixed model for repeated measures was used to analyze change from baseline in IC.	Baseline, Week 26 (Day 183-184)
Secondary	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Individual Timepoints at Week 26	Mixed model for repeated measures was used to analyze change from baseline in FEV1. Baseline FEV1 is defined as the average of the -45 min and -15 min FEV1 values taken on Day 1 prior to first dose.	Baseline, Week 26 (Day 183-184)
Secondary	Change From Baseline in the Percentage of Days With no Rescue Medication Use Over the 26 Weeks	Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. change from baseline in percentage of days without rescue medication usage over 26 weeks was analyzed.	Baseline, 26 Weeks
Secondary	Change From Baseline in Mean Daily COPD Symptom Score at Week 26	Patients reported symptoms by using an electronic diary. The mean daily total symptom score, the mean morning symptom score and the mean evening symptom score were calculated for each patient over 26 weeks. Each symptom measured in a numeric rating scale of 0-10; 0 indicates no symptom and 10 indicates severe symptom. 0 is no waking due to symptoms, 1 woke up once, 2 woke up more than once due to symptoms ; 10 was the worst score.The daily score for an individual symptom score was the worst of the morning and evening scores on a particular day. If either the morning or evening score was missing for a symptom then the non-missing value was taken as the worst. A negative change indicates improvement. Only the scores for the 6 COPD symptoms (respiratory symptoms, cough, wheeze, production of sputum, sputum color, and breathlessness) were used to derive the total symptom score	Baseline, 26 Weeks
Secondary	Number of Patients With Adverse Events, Serious Adverse Events and Death	This endpoint reports patients affected by any adverse events (AE), serious adverse events (SAE) and death. Only treatment emergent AE, SAE, deaths are reported for this endpoint.	26 Weeks