Efficacy, Safety, and Tolerability of NVA237 Compared to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease Clinical Trial

— GLOW5  

Official title:

A 12-week Treatment, Randomized, Blinded, Double-dummy, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of NVA237 (50 µg o.d.) Compared to Tiotropium (18 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01613326
• Other study ID #: CNVA237A2314
• Secondary ID: 2011-000960-93
• Status: Completed
• Phase: Phase 3
• First received: February 17, 2012
• Last updated: April 22, 2014
• Start date: June 2012
• Est. completion date: January 2013

Study information

• Verified date: April 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaCanada: Health CanadaCroatia: Agency for Medicinal Product and Medical DevicesCzech Republic: State Institute for Drug ControlGuatemala: Ministry of Public Health and Social AssistanceEstonia: The State Agency of MedicineFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesIndia: Ministry of HealthKorea: Food and Drug AdministrationLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthPhilippines: Department of HealthPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSouth Africa: Department of HealthTaiwan : Food and Drug AdministrationTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This study compared the efficacy and safety of NVA237 with tiotropium in patients with moderate to severe COPD. Tiotropium belongs to the same drug class as NVA237.

Description:

This was a randomized, blinded, double-dummy, parallel-group 12-week study to assess the efficacy, safety, and tolerability of NVA237 (50 μg o.d.) compared to tiotropium (18 μg o.d.) in patients with chronic obstructive pulmonary disease (COPD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 657
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Patients with moderate to severe stable COPD (Stage II or Stage III) according to the current GOLD Guidelines (GOLD 2010).

• Patients with a post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) = 30% and < 80% of the predicted normal, and a post-bronchodilator FEV1/ Forced Vital Capacity (FVC) < 0.70 at screening

• 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 yrs, or ½ pack/day x 20 yrs).

• Symptomatic patients, according to daily electronic diary data between Visit 2 (Day -14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3.

Exclusion Criteria:

• Pregnant or nursing (lactating) women

• Patients who, in the judgment of the investigator, or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition before Visit 1.

• Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (BPH patients who are stable on treatment can be considered).

• Patients receiving medications in the classes listed in the protocol as prohibited.

Other protocol-defined inclusion/exclusion criteria apply and can be found in the study protocol

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• NVA237
NVA237 50 µg inhalation capsules once a day, delivered via SDDPI
• Tiotropium
Tiotropium 18 µg once a day delivered via HandiHaler® device
• Placebo to tiotropium
Placebo to tiotropium 18 µg o.d. once a day delivered via HandiHaler® device.
• Placebo to NVA237
Placebo to NVA237 50 µg once a day delivered via SDDPI
• salbutamol/albuterol
salbutamol/albuterol given as a rescue medication via inhaler when needed

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Gatineau	Quebec
Canada	Novartis Investigative Site	Mirabel	Quebec
Canada	Novartis Investigative Site	St-Charles-Borromée	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Croatia	Novartis Investigative Site	Sisak
Croatia	Novartis Investigative Site	Zagreb
Croatia	Novartis Investigative Site	Zagreb
Czech Republic	Novartis Investigative Site	Cvikov
Czech Republic	Novartis Investigative Site	Liberec
Czech Republic	Novartis Investigative Site	Praha 10
Czech Republic	Novartis Investigative Site	Praha 4
Czech Republic	Novartis Investigative Site	Praha 6
Czech Republic	Novartis Investigative Site	Rudna
Czech Republic	Novartis Investigative Site	Teplice
Czech Republic	Novartis Investigative Site	Zatec
Estonia	Novartis Investigative Site	Paide
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
France	Novartis Investigative Site	Beuvry
France	Novartis Investigative Site	Lyon cedex 04
France	Novartis Investigative Site	Nantes
France	Novartis Investigative Site	Reims
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Rüdersdorf
Germany	Novartis Investigative Site	Wiesbaden
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Chennai - Tamil Nadu
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Guntur	Andhra Pradesh
India	Novartis Investigative Site	Nagpur	Maharashtra
Korea, Republic of	Novartis Investigative Site	Bucheon-Si	Gyeonggi-Do
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Alytus
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Utena
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius
Philippines	Novartis Investigative Site	Bulacan
Philippines	Novartis Investigative Site	Lipa City	Batangas
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Wroclaw
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Gatesville
Taiwan	Novartis Investigative Site	Chia-Yi
Taiwan	Novartis Investigative Site	Chiayi
Taiwan	Novartis Investigative Site	Niaosong Township
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei County

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Canada,  Croatia,  Czech Republic,  Estonia,  France,  Germany,  Guatemala,  India,  Korea, Republic of,  Latvia,  Lithuania,  Philippines,  Poland,  South Africa,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment (Non-inferiority Analysis)	Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23hours 15min and 23 hours 45min post dosing. ANCOVA model: Trough FEV1 = treatment + baseline FEV1 + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center (region). This analysis excluded values within 6 hours of rescue medication use or 7 days of systemic corticosteroid use.	Week 12	No
Secondary	Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment (Analysis of Superiority)	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 15min and 23h 45min post dosing. ANCOVA model: Trough FEV1 = treatment + baseline FEV1 + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center(region). This analysis excluded values within 6 hours of rescue medication use or 7 days of systemic corticosteroid.	Week 12	No
Secondary	Transition Dyspnea Index (TDI) Focal Score After 4 Weeks and 12 Weeks of Treatment	Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.; ANCOVA model: TDI focal score = treatment + Baseline dyspnea index (BDI) + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center(region). Center is included as a random effect nested within region.	Weeks 4 and 12	No
Secondary	St. George's Respiratory Questionnaire Total Score After 12 Weeks of Treatment	St. George's Respiratory Questionnaire (SGRQ) is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. ANCOVA model: SGRQ total score = treatment + baseline SGRQ score + baseline ICS use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center (region).	Week 12	No
Secondary	Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Used Over the 12 Week Treatment	A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours.; Baseline mean daily, daytime and nighttime (combined) number of puffs is defined as the average of the respective number of puffs. Only patients with a value at both baseline and post-baseline visits were included.	Baseline and Day 1 to Week 12	No
Secondary	Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Week 4	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.; Trough FEV1 is defined as the average of the post-dose 23 h 15 min and the 23 h 45 min FEV1 values. Trough assessments taken outside 22 h 45 min - 24 h 15 min are excluded from this analysis.; ANCOVA model: Trough FEV1 = treatment + baseline FEV1 + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center(region). Center is included as a random effect nested within region.	Day 1 and Week 4	No
Secondary	Peak Forced Expiratory Volume in 1 Second (FEV1) During 5 Min to 4 Hours Post-dose, at Day 1 and Week 12	Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded during first 4 hours post dose. ANCOVA model: Peak FEV1 = treatment + baseline FEV1 + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center (region). Center is included as a random effect nested within region. This analysis excludes values within 6 hours of rescue medication use or 7 days of systemic corticosteroid use.	5 min to 4 hours post-dose at Day 1 and Week 12	No
Secondary	Inspiratory Capacity (IC) at Each Time-point, by Visit	IC was measured with spirometry conducted according to internationally accepted standards. ANCOVA model: IC = treatment + baseline IC + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center(region). Center is included as a random effect nested within region.	(25 min, 1 h 55 min, 3 h 55 min, 23 h 40 min Day 1), (-20 min, 25 min, 23 h 40 min Week 4),(-20 min, 25 min, 1 h 55 min, 3 h 55 min, 23 h 40 min Week 12)	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) at Each Time-point by Visit	Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was analyzed using Analysis of Covariance (ANCOVA) model: FEV1 = treatment + baseline FEV1 + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center(region). Center is included as a random effect nested within region.	(5,15,30 min, 1, 2,3,4 h, 23h 15 min and 23h 45 min postdose of Day 1), (-45, -15 min predose, 5,15,30 min, 1h, 23h 15 min and 23h 45 min postdose of Week 4), (-45, -15 min predose, 5,15,30 min, 1, 2, 3,4 h, 23h 15 min and 23h 45 min postdose of Week 12)	No
Secondary	Forced Vital Capacity (FVC) at Each Time-point by Visit	Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. ANCOVA model: FVC = treatment + baseline FVC + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center(region). Center is included as a random effect nested within region.	(5,15,30 min, 1, 2,3,4 h, 23h 15 min and 23h 45 min postdose of Day 1), (-45, -15 min predose, 5,15,30 min, 1h, 23h 15 min and 23h 45 min postdose of Week 4), (-45, -15 min predose, 5,15,30 min, 1, 2, 3,4 h, 23h 15 min and 23h 45 min postdose of Week 12)	No
Secondary	Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (5 Min-4 h) Post-dose	Forced Expiratory Volume in one second (FEV1) was measured with spirometry conducted according to internationally accepted standards.; Area Under the Curve (AUC) is calculated using the trapezoidal rule using the existing FEV1 measurements (i.e., the missing FEV1 measurements are not interpolated).; ANCOVA model: FEV1 AUC = treatment + baseline FEV1 + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center(region). Center is included as a random effect nested within region.	Day 1 and week 12	No
Secondary	Event Free Rate at Weeks 4, 8 and 12 After Treatment	Event free rate was calculated as a percentage of participants who did not experience any moderate or severe COPD exacerbation leading to hospitalization/treatment with systemic corticosteroids/treatment with antibiotics. The event free rate reflects the percent of patients who did NOT have an exacerbation by 4, 8 and 12 weeks. Event-free rates are calculated at the end of the specified weeks (i.e. Day 29, Day 57 and Day 85) by the Kaplan Meier method.	Weeks 4, 8 and 12	Yes
Secondary	Mean Daily, Daytime and Nighttime (Combined) Symptom Scores Over the 12 Week Treatment Period	Participants completed eDiaries providing scores 0 to 3 for symptoms: Cough and wheeze (none, mild, moderate, severe); sputum volume (none, less than 5 mL, 5-25 mL, >25 mL); sputum color (none, white-grey, yellow, green); lowest level of activity causing breathlessness (never or only when running, when walking uphill or upstairs, when walking on flat ground, at rest). Symptoms in the morning, for the previous night (no waking due to symptoms, woke up once due to symptoms, woke up more than once due to symptoms, woke up frequently or could not sleep due to symptoms). Symptoms experienced during the day that had prevented them for performing normal activities (not at all, a little, quite a lot, completely). The mean change from baseline in the total scores and in the individual scores was summarized by treatment. Only participants with a value at both baseline and post-baseline were included. Possible total scores 0-18 (night); 0-36 (day). A higher score means worsening of symptoms.	12 weeks	No