search
Back to results

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

Primary Purpose

Chronic Obstructive Pulmonary Disease (COPD)

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
NVA237
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease (COPD) focused on measuring Chronic obstructive pulmonary disease (COPD), NVA237

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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  • Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis (unless confirmed by imaging to be no longer active) or clinically significant bronchiectasis, sarcoidosis and interstitial lung disorder.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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

NVA237

Placebo

Arm Description

NVA237 50 µg once daily delivered via a single dose dry powder inhaler

Placebo once daily delivered via a single dose dry powder inhaler

Outcomes

Primary Outcome Measures

Trough Forced Expiratory Volume in One Second (FEV1)
Baseline FEV1 was defined as the average of the -45 min and -15 min FEV1 values taken on day 1 prior to the first dose of study medication. Trough FEV1 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. 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

Transition Dyspnea Index (TDI) Score
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.
Change From Baseline in Daily Rescue Medication Use (Number of Puffs)
The participant 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 was analyzed.
24h Trough FEV1
Trough FEV1 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)
FEV1 and FVC were measured using central spirometry according to ATS/ERS standardization. Both were analyzed using the same MIXED model as specified for the primary analysis.
Peak FEV1
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
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.
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptoms (Cough, Wheezing, Shortness of Breath, Sputum Volume, Sputum Color and Night Time Awakenings)
In an electronic diary, the participant responded to 6 questions twice daily to report on the degree of symptoms over the past 12 hours of the morning and evening. The questions covered the participant's degree of overall symptoms, and degrees of individual symptoms of coughing, wheezing, amount of sputum, color of sputum and breathlessness. Each question scored from 0 to 3 where 0 represented no symptom present and 3 represented the worst degree of that symptom. A negative change in symptom score indicates improvement.
Time to First Moderate or Severe COPD Exacerbation
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.
Number of Moderate and Severe COPD Exacerbations
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.
The Total Score of the St George's Respiratory Questionnaire (SGRQ)
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 investigators site.

Full Information

First Posted
March 27, 2012
Last Updated
July 16, 2014
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT01566604
Brief Title
Efficacy, Safety and Tolerability of NVA237 in Patients With Chronic Obstructive Pulmonary Disease
Acronym
GLOW7
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease (COPD)
Keywords
Chronic obstructive pulmonary disease (COPD), NVA237

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
460 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NVA237
Arm Type
Experimental
Arm Description
NVA237 50 µg once daily delivered via a single dose dry powder inhaler
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo once daily delivered via a single dose dry powder inhaler
Intervention Type
Drug
Intervention Name(s)
NVA237
Intervention Description
Delivered via a single dose dry powder inhaler
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Delivered via a single dose dry powder inhaler
Primary Outcome Measure Information:
Title
Trough Forced Expiratory Volume in One Second (FEV1)
Description
Baseline FEV1 was defined as the average of the -45 min and -15 min FEV1 values taken on day 1 prior to the first dose of study medication. Trough FEV1 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. 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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Transition Dyspnea Index (TDI) Score
Description
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.
Time Frame
Baseline, week 12, week 26
Title
Change From Baseline in Daily Rescue Medication Use (Number of Puffs)
Description
The participant 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 was analyzed.
Time Frame
Baseline, 26 weeks
Title
24h Trough FEV1
Description
Trough FEV1 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.
Time Frame
Day 1, Week 26
Title
FEV1 and Forced Vital Capacity (FVC)
Description
FEV1 and FVC were measured using central spirometry according to ATS/ERS standardization. Both were analyzed using the same MIXED model as specified for the primary analysis.
Time Frame
Day 1 at 5, 15, 30 minutes (min) and 1 hour (h) post dose; days 2, 86, 184 at 23 (h) 15 min and 23 h 45 min post dose; days 29, 85, 183 at -45 and -15 min pre-dose and 5, 15, and 30 min post dose
Title
Peak FEV1
Description
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.
Time Frame
Day 1, week 12, week 26
Title
Standardized FEV1 Area Under the Curve (AUC(5 Min-4 h)) Post-dose
Description
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.
Time Frame
Day 1, week 12, week 26
Title
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptoms (Cough, Wheezing, Shortness of Breath, Sputum Volume, Sputum Color and Night Time Awakenings)
Description
In an electronic diary, the participant responded to 6 questions twice daily to report on the degree of symptoms over the past 12 hours of the morning and evening. The questions covered the participant's degree of overall symptoms, and degrees of individual symptoms of coughing, wheezing, amount of sputum, color of sputum and breathlessness. Each question scored from 0 to 3 where 0 represented no symptom present and 3 represented the worst degree of that symptom. A negative change in symptom score indicates improvement.
Time Frame
Baseline, 26 weeks
Title
Time to First Moderate or Severe COPD Exacerbation
Description
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.
Time Frame
26 weeks
Title
Number of Moderate and Severe COPD Exacerbations
Description
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.
Time Frame
26 weeks
Title
The Total Score of the St George's Respiratory Questionnaire (SGRQ)
Description
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 investigators site.
Time Frame
Week 12, week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100023
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Novartis Investigative Site
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530021
Country
China
Facility Name
Novartis Investigative Site
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050000
Country
China
Facility Name
Novartis Investigative Site
City
Changsha City
State/Province
Hunan
ZIP/Postal Code
410011
Country
China
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
Novartis Investigative Site
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215004
Country
China
Facility Name
Novartis Investigative Site
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Facility Name
Novartis Investigative Site
City
Shengyang
State/Province
Liaoning
ZIP/Postal Code
110016
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200433
Country
China
Facility Name
Novartis Investigative Site
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Novartis Investigative Site
City
Chongqing
ZIP/Postal Code
400037
Country
China
Facility Name
Novartis Investigative Site
City
Chongqing
ZIP/Postal Code
400038
Country
China
Facility Name
Novartis Investigative Site
City
Chongqing
ZIP/Postal Code
400042
Country
China
Facility Name
Novartis Investigative Site
City
Guang zhou
ZIP/Postal Code
510080
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
ZIP/Postal Code
300052
Country
China
Facility Name
Novartis Investigative Site
City
Dehli
State/Province
New Delhi
ZIP/Postal Code
110063
Country
India
Facility Name
Novartis Investigative Site
City
Coimbatore
State/Province
Tamil Nadu
ZIP/Postal Code
641 045.
Country
India
Facility Name
Novartis Investigative Site
City
Daejeon
ZIP/Postal Code
301-804
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Incheon
ZIP/Postal Code
403-010
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
130-709
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
137-701
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
150-713
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Bulacan
ZIP/Postal Code
3020
Country
Philippines
Facility Name
Novartis Investigative Site
City
Las Pinas
ZIP/Postal Code
1740
Country
Philippines
Facility Name
Novartis Investigative Site
City
Manila
ZIP/Postal Code
1000
Country
Philippines
Facility Name
Novartis Investigative Site
City
Quezon City
ZIP/Postal Code
1100
Country
Philippines

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs