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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


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
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