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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01566604
• Other study ID #: CNVA237A2309
• Status: Completed
• Phase: Phase 3
• First received: March 27, 2012
• Last updated: July 16, 2014
• Start date: March 2012
• Est. completion date: June 2013

Study information

• Verified date: July 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationChina: Ethics Committee China: Ministry of HealthChina: Food and Drug AdministrationIndia: Central Drugs Standard Control OrganizationIndia: Department of Atomic EnergyIndia: Drugs Controller General of IndiaIndia: Indian Council of Medical ResearchIndia: Institutional Review BoardIndia: Ministry of HealthIndia: Ministry of Science and TechnologyIndia: Science and Engineering Research CouncilKorea: Food and Drug AdministrationPhilippines: Department of HealthPhilippines: Bureau of Food and DrugsChina: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 460
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 a-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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/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 (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• NVA237
Delivered via a single dose dry powder inhaler
• Placebo
Delivered via a single dose dry powder inhaler

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changsha City	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Guang zhou
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanning	Guangxi
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shengyang	Liaoning
China	Novartis Investigative Site	Shijiazhuang	Hebei
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Xi'an	Shanxi
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Dehli	New Delhi
Korea, Republic of	Novartis Investigative Site	Daejeon
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Philippines	Novartis Investigative Site	Bulacan
Philippines	Novartis Investigative Site	Las Pinas
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  India,  Korea, Republic of,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 weeks	No
Secondary	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.	Baseline, week 12, week 26	No
Secondary	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.	Baseline, 26 weeks	No
Secondary	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.	Day 1, Week 26	No
Secondary	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.	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	No
Secondary	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.	Day 1, week 12, week 26	No
Secondary	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.	Day 1, week 12, week 26	No
Secondary	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.	Baseline, 26 weeks	No
Secondary	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.	26 weeks	No
Secondary	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.	26 weeks	No
Secondary	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.	Week 12, week 26	No