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Efficacy, Safety, and Tolerability of NVA237 Compared to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD) (GLOW5)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01613326
First received: February 17, 2012
Last updated: March 14, 2013
Last verified: March 2013
History of Changes
  Purpose

This study will compare the efficacy and safety of NVA237 with tiotropium in patients with moderate to severe COPD. Tiotropium has been selected as the comparator as it is approved and accepted as standard of care for the control of symptoms of COPD. Tiotropium belongs to the same drug class as NVA237.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
 Drug: NVA237
Drug: Tiotrpium
Drug: Placebo to tiotropium
Drug: Placebo to NVA237
Drug: salbutamol/albuterol
 Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 FEV1 at 23 h 15 min and 23 h 45 min after the morning dose of study drug. Analysis will be performed using a mixed model containing treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.


Secondary Outcome Measures:
  • Transition Dyspnea Index (TDI) Focal Score [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Transition dyspnea index (TDI) captures changes from baseline in 3 domains: functional impairment, magnitude of task, and magnitude of effort; the lower the score the worse the severity of dyspnea. The TDI domains are summed for the transition focal score ranging from - 9 to 9; minus scores indicate deterioration. The TDI focal score after 12 weeks of treatment will be analyzed using a mixed model which contains treatment as a fixed effect with the BDI focal score, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.

  • The mean change from baseline in the daily number of puffs of rescue medication [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    The total number of puffs of rescue medication per day over the whole active treatment period will be calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. The mean change from baseline in the daily number of puffs of rescue medication will be analyzed using a mixed model which contains treatment as a fixed effect with baseline daily rescue use, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.

  • The mean change from baseline in the daytime number of puffs of rescue medication. [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    The total number of daytime puffs of rescue medication per day over the whole active treatment period will be calculated and divided by the total number of days with non-missing rescue data to derive the mean daytime number of puffs of rescue medication. The mean change from baseline in the daytime number of puffs of rescue medication will be analyzed using a mixed model which contains treatment as a fixed effect with baseline daytime rescue medication use, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.

  • The mean change from baseline in the nighttime number of puffs of rescue medication [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Total number of nighttime puffs of rescue medication per day over the whole active treatment period will be calculated and divided by the total number of days with non-missing rescue data to derive the mean nighttime number of puffs of rescue medication. The mean change from baseline in the nighttime number of puffs of rescue medication will be analyzed using a mixed model which contains treatment as a fixed effect with baseline nighttime rescue medication use, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.

  • The percentage of 'days with no rescue use' [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be analyzed using a mixed model which contains treatment as a fixed effect with baseline 'days with no rescue use', FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates. This model will also include smoking status at baseline (current/ex-smoker) history of ICS use as fixed effects and center as a random effect.

  • Mean trough FEV1 [ Time Frame: Day 1 and week 4 ] [ Designated as safety issue: No ]
    Trough FEV1 is defined as the average of FEV1 at 23 h 15 min and 23 h 45 min after the morning dose of study drug. Analysis will be performed using a mixed model containing treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates. The model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.

  • Mean peak FEV1 [ Time Frame: Day 1 and week 4 ] [ Designated as safety issue: No ]
    Peak FEV1 is defined as the maximum FEV1 0-4 h post-dose. Analysis will be performed using a mixed model containing treatment as a fixed effect with the baseline peak FEV1, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates. The model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.

  • FEV1 [ Time Frame: At individual time-points on Day 1, Week 4 and Week 12 ] [ Designated as safety issue: No ]
    FEV1 will be analyzed using a mixed model containing treatment as a fixed effect with the baseline FEV1, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates. The model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.

  • Forced Vital Capacity (FVC) [ Time Frame: At individual time-points on Day 1, Week 4 and Week 12 ] [ Designated as safety issue: No ]
    FVC is the total volume of air that the patient can forcibly exhale in one breath. FVC will be analyzed using a mixed model containing treatment as a fixed effect with baseline FVC, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates. The model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.

  • Inspiratory Capacity (IC) [ Time Frame: At individual time-points on Day 1, Week 4 and Week 12 ] [ Designated as safety issue: No ]
    IC is the volume of air breathed in by a maximum inspiration at the end of a normal expiration. IC will be analyzed using a mixed model containing treatment as a fixed effect with the baseline IC, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates. The model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.

  • FEV1 AUC (5min-4h) [ Time Frame: Day 1 and week 12 ] [ Designated as safety issue: No ]
    The standardized (with respect to time) area under the curve (AUC) for FEV1 will be analyzed using a mixed model containing treatment as a fixed effect with baseline FEV1AUC(5min-4h), FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates. The model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.

  • Percentage of nights with 'no nighttime awakenings' [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms. The 'percentage of nights with 'no nighttime awakenings' will be analyzed using a mixed model which contains treatment as a fixed effect with baseline 'nights with no nighttime awakenings' , FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.

  • Percentage of days with 'no daytime symptoms' [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    A day with 'no daytime symptoms' is defined from the diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours. The percentage of days with 'no daytime symptoms' will be analyzed as a mixed model which contains treatment as a fixed effect with baseline 'days with no daytime symptoms', FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.

  • Percentage of 'days able to perform usual daily activities' [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Total number of days 'able to perform usual daily activities' (ie, patient not prevented from performing usual daily activities due to respiratory symptoms) over the whole treatment period will be divided by the total number of days where diary recordings have been made. The percentage of days 'able to perform usual daily activities' will be analyzed as a mixed model containing treatment as a fixed effect with baseline 'days able to perform usual daily activities', FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.

  • Symptom scores [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Daily symptom score is calculated as the sum of the worst of the morning and evening assessments for each symptom (cough, wheeze, sputum color/production, and breathlessness). Mean total symptom scores and mean individual symptom scores will be calculated for the whole study period. The mean change from baseline in the total scores and in the individual scores will be analyzed as a mixed model which contains treatment as a fixed effect with baseline symptom scores, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates.

  • Time to first moderate /severe COPD exacerbation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    The time to the first moderate or severe COPD exacerbation is the study day on which the patient experienced the first exacerbation.

    A COPD exacerbation is defined as:

    A worsening of the following two or more major symptoms for at least 2 consecutive days: dyspnea, sputum volume, sputum purulence OR

    A worsening of any 1 major symptom together with an increase of any 1 of the following minor symptoms for at least 2 consecutive days:

    sore throat, colds (nasal discharge and/or nasal congestion), fever without other cause, cough, wheeze.


  • Rate of moderate / severe COPD exacerbations [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The COPD exacerbation rate is the number of moderate or severe exacerbations per year and is calculated as the total number of moderate or severe exacerbations/total number of treatment years. A COPD exacerbation is defined as: A worsening of the following two or more major symptoms for at least 2 consecutive days: dyspnea, sputum volume, sputum purulence OR A worsening of any 1 major symptom together with an increase of any 1 of the following minor symptoms for at least 2 consecutive days: sore throat, colds (nasal discharge and/or nasal congestion), fever without other cause, cough, wheeze.

  • Safety variables [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    All study emergent adverse events including COPD exacerbations will be summarized and listed.

  • Electrocardiogram (ECG) [ Time Frame: Baseline and day 1 and week 12 ] [ Designated as safety issue: Yes ]
    Notable QTc values and changes from baseline will be summarized.

  • Blood pressure [ Time Frame: Baseline and individual time-points on Days 1, 2, 28,29,84 ] [ Designated as safety issue: Yes ]
    Notable values for vital signs and change from baseline will be summarized.

  • Quality of Life Assessment with St George's Respiratory Questionnaire (SGRQ) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    SGRQ is a health related quality of life questionnaire consisting of 3 components: symptoms, activity and impacts. Higher values correspond to greater impairment of quality of life. The SGRQ score will be analyzed using a mixed model which contains treatment as a fixed effect with the SGRQ baseline score, FEV1 prior to inhalation of short acting bronchodilator, and FEV1 post inhalation of short acting bronchodilator as covariates. This model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.

  • Radial pulse [ Time Frame: Baseline and individual time-points on Days 1, 2, 28,29,84 ] [ Designated as safety issue: Yes ]
    Notable values for vital signs and change from baseline will be summarized.

  • Hemoglobin [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Changes in laboratory data from baseline to post baseline will be summarized.

  • White blood cells [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Changes in laboratory data from baseline to post baseline will be summarized.

  • Creatinine [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Changes in laboratory data from baseline to post baseline will be summarized.

  • Blood glucose [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Changes in laboratory data from baseline to post baseline will be summarized.


Enrollment: 980
Study Start Date: June 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NVA237
NVA237 50 µg inhalation capsules o.d., delivered via single-dose dry-powder inhaler (SDDPI) plus placebo to tiotropium delivered via the manufacturer's proprietary inhalation device (HandiHaler®)
 Drug: NVA237
Participants received NVA 237 50 µg delivered via a single-dose dry powder inhaler (SDDPI) plus placebo to tiotropium delivered via the manufacturer's proprietary inhalation device (HandiHaler®) once daily in the morning for 12 weeks. Participants are permitted to take salbutamol/albuterol as a rescue medication.
Drug: Placebo to tiotropium
Participants received NVA 237 50 µg delivered via a single-dose dry powder inhaler (SDDPI) plus placebo to tiotropium delivered via the manufacturer's proprietary inhalation device (HandiHaler®) once daily in the morning for 12 weeks. Participants are permitted to take salbutamol/albuterol as a rescue medication.
Drug: salbutamol/albuterol
salbutamol/albuterol given as a rescue medication via inhaler
Active Comparator: Tiotropium
Tiotropium 18 μg o.d. delivered via the manufacturer's proprietary inhalation device (HandiHaler®) plus placebo to NVA237 50 µg o.d. delivered via single-dose dry-powder inhaler (SDDPI)
 Drug: Tiotrpium
Participants receive tiotropium 18 μg delivered via the manufacturer's proprietary inhalation device (HandiHaler®) plus placebo to NVA 237 once daily in the morning for 12 weeks. Participants are permitted to take salbutamol/albuterol as a rescue medication
Drug: Placebo to NVA237
Participants receive tiotropium 18 μg delivered via the manufacturer's proprietary inhalation device (HandiHaler®) plus placebo to NVA 237 once daily in the morning for 12 weeks. Participants are permitted to take salbutamol/albuterol as a rescue medication.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible, patients have to fulfill all the 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 FEV1 ≥ 30% and < 80% of the predicted normal, and a post-bronchodilator FEV1/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 may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01613326

  Show 76 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01613326     History of Changes
Other Study ID Numbers: CNVA237A2314, 2011-000960-93
Study First Received: February 17, 2012
Last Updated: March 14, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Czech Republic: State Institute for Drug Control
Guatemala: Ministry of Public Health and Social Assistance
Estonia: The State Agency of Medicine
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
India: Ministry of Health
Korea: Food and Drug Administration
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Philippines: Department of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Africa: Department of Health
Taiwan : Food and Drug Administration
Turkey: Ministry of Health

Keywords provided by Novartis:
COPD

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Albuterol
Tiotropium
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
 Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on May 19, 2013