Efficacy, Safety and Tolerability of NVA237 in Patients With Chronic Obstructive Pulmonary Disease (GLOW7)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01566604
First received: March 27, 2012
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

This study will assess of the efficacy and safety of a once-daily, 50µg inhalation of NVA237 in moderate to severe chronic obstructive pulmonary disease (COPD) patients over 26 weeks treatment.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: NVA237
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 26-week Treatment, Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of NVA237 (50 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in one second (FEV1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Trough FEV1 after 12 weeks of treatment was defined as the mean of the post-dose 23 h 15 min and the 23 h 45 min FEV1 values. FEV1 was measured using central spirometry according to ATS/ERS standardization. The trough FEV1 was analyzed using a MIXED model for the full analysis set population. The model contained treatment as a fixed effect with the baseline FEV1 measurement, FEV1 prior to inhalation of short acting bronchodilator, FEV1 45 min post inhalation of short acting bronchodilator and baseline inhaled corticosteroids (ICS) use as covariates.


Secondary Outcome Measures:
  • The total score of the St George's Respiratory Questionnaire (SGRQ) [ Time Frame: Week 12, week 26 ] [ Designated as safety issue: No ]
    SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity and impacts. The lowest possible score is zero and the highest possible score is 100. Higher scores correspond to greater impairment in quality of life. The health-related quality of life was measured using SGRQ. It was completed by the participant at the investigator's site.

  • Transition Dyspnea Index (TDI) score [ Time Frame: Baseline, week 12, week 26 ] [ Designated as safety issue: No ]
    Dyspnea was measured at baseline using the Baseline Dyspnea Index (BDI) and during the treatment period using the TDI, which captures changes from baseline. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort, and each domain scored from -3 (major deterioration) to +3 (major improvement), giving an overall score of -9 to +9. A negative score indicates deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.

  • Daily rescue medication use (number of puffs) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    The participoant recorded the rescue medication taken in an electronic diary between visits and in the spirometry device during study visits. Daytime and nighttime rescue medication use (number of puffs) over 26 weeks, daily daytime and nighttime rescue medication use (number of puffs) at weekly intervals, and percentage of 'days with no rescue use' over 26 weeks were analyzed.

  • 24h trough FEV1 [ Time Frame: Day 2, Week 26 ] [ Designated as safety issue: No ]
    Trough FEV1 of 26 weeks of treatment was defined as the mean of the post-dose 23 h 15 min and the 23 h 45 min FEV1 values. This was measured using central spirometry according to ATS/ERS standardization. This was analyzed using the same MIXED model as specified for the primary analysis.

  • FEV1 and Forced Vital Capacity (FVC) [ Time Frame: Day 1, Day 2, Weeks 5, 12, 26 and 27 ] [ Designated as safety issue: No ]
    FEV1 and FVC were measured at 45min and 15min pre-dose and up to 4h post dose at day 1, week 5, week 12 and week 26, and also measured at 23h15min and 23h45min post dose at day 2, week 12 and week 27, using central spirometry according to ATS/ERS standardization. Both were analyzed using the same MIXED model as specified for the primary analysis.

  • Peak FEV1 [ Time Frame: Day 1, week 12, week 26 ] [ Designated as safety issue: No ]
    Peak FEV1 was defined as the maximum FEV1 0-4 h post-dose. Peak Fev1 was measured at 45min and 15min pre-dose and up to 4h post dose at day 1, week 12 and week 26, using central spirometry according to ATS/ERS standardization. It was analyzed using the same MIXED model as specified for the primary analysis.

  • Standardized FEV1 Area Under the Curve (AUC(5 min-4 h)) post-dose [ Time Frame: Day 1, week 12, week 26 ] [ Designated as safety issue: No ]
    The standardized (with respect to time) AUC for FEV1 was calculated between 5 min and 4h post morning dose at day 1, week 12 and week 26. The AUC (5 min-4 h) for FEV1 at each visit was analyzed using the same MIXED model as specified for the primary analysis.

  • Chronic Obstructive Pulmonary Disease (COPD) symptoms (cough, wheezing, shortness or breath, sputum volume, sputum color and night time awakenings) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Morning and evening daily clinical symptoms were recorded in an electronic diary.

  • Time to first COPD exacerbation [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    A COPD exacerbation was defined as a worsening of the following two or more major symptoms for at least 2 consecutive days:1) dyspnea; 2) sputum volume; 3) sputum purulence; or defined as a worsening of any 1 major symptom together with an increase in any 1 of the following minor symptoms for at least 2 consecutive days: 1) sore throat; 2) colds (nasal discharge and/or nasal congestion); 3) fever without other cause; 4) cough; 5) wheeze. COPD exacerbations were recorded in the patient diary and other source documents.

  • COPD exacerbation rate [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    COPD exacerbations were recorded in the patient diary and other source documents. The rate of COPD exacerbations during the 26 week treatment period was analyzed using a generalized linear model assuming a negative binomial distribution.


Enrollment: 458
Study Start Date: March 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NVA237
NVA237 50 µg once daily delivered via a single dose dry powder inhaler
Drug: NVA237
Delivered via a single dose dry powder inhaler
Placebo Comparator: Placebo
Placebo once daily delivered via a single dose dry powder inhaler
Drug: Placebo
Delivered via a single dose dry powder inhaler

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure
  • With moderate to severe stable COPD (Stage II or Stage III).
  • Current or ex-smokers who have a smoking history of at least 10 pack years (Ten pack- years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years).
  • Post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 at Visit 2 (Day -14) (post means: record FEV1 and FVC 45 min after administering ipratropium).
  • 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:

  • With a history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
  • Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count > 600/mm3 (at Visit 2) or onset of symptoms prior to age 40 years. Patients without asthma but who have a blood eosinophil count >600/mm3 at Visit 2 are excluded.
  • Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis (unless confirmed by imaging to be no longer active) or clinically significant bronchiectasis, sarcoidosis and interstitial lung disorder.
  • Patients with lung lobectomy or lung volume reduction or lung transplantation.
  • Patients with known history and diagnosis of α-1 antitrypsin deficiency.
  • Patients who have had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to Visit 1 Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566604

  Show 32 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: NCT01566604     History of Changes
Other Study ID Numbers: CNVA237A2309
Study First Received: March 27, 2012
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration
China: Ethics Committee China: Ministry of Health
China: Food and Drug Administration
India: Central Drugs Standard Control Organization
India: Department of Atomic Energy
India: Drugs Controller General of India
India: Indian Council of Medical Research
India: Institutional Review Board
India: Ministry of Health
India: Ministry of Science and Technology
India: Science and Engineering Research Council
Korea: Food and Drug Administration
Philippines: Department of Health
Philippines: Bureau of Food and Drugs
China: Ministry of Health

Keywords provided by Novartis:
Chronic obstructive pulmonary disease (COPD)
NVA237

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 22, 2014