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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Multicenter, Randomized, Blinded, Active-controlled, Parallel-group Study to Compare the Efficacy, Tolerability and Safety of NVA237 Compared to Tiotropium Added on to Fluticasone/Salmeterol in Patients With Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01513460
• Other study ID #: CNVA237AAU01
• Status: Completed
• Phase: Phase 3
• First received: January 16, 2012
• Last updated: December 23, 2014
• Start date: April 2012
• Est. completion date: December 2013

Study information

• Verified date: December 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy, tolerability and safety of NVA237 compared to tiotropium when added on to fluticasone/salmeterol in patients with chronic obstructive pulmonary disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 773
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Patients with Moderate to Severe COPD (Stage II or Stage III) according to the GOLD 2010 guideline

• Current or ex-smokers who have a smoking history of at least 10 pack years

• Qualifying FEV1 at Visit 2 (day -7)

Exclusion Criteria:

• Patients with a history of asthma or a history of high blood eosinophil count (>600/mm³)

• Patients with concomitant pulmonary disease

• Patients with lung lobectomy or lung volume reduction or lung transplantation

• Patients with a-1 antitrypsin deficiency

• Patients who have had live attenuated vaccinations within 30 days prior to screening visit or during run-in period

Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• NVA237 50µg once daily
NVA237 50 µg o.d., delivered via single-dose dry-powder inhaler (SDDPI)
• Tiotropium 18µg once daily
Tiotropium 18 µg o.d. delivered via a proprietary inhalation device
• Flu/Sal
Flu/Sal 500/50 µg b.i.d. delivered via a proprietary inhalation device
• NVA237 placebo + Tiotropium placebo.
Tiotropium 18 µg o.d. delivered via a proprietary inhalation device

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Arundel	Queensland
Australia	Novartis Investigative Site	Aspley	Queensland
Australia	Novartis Investigative Site	Baulkham Hills	New South Wales
Australia	Novartis Investigative Site	Beenleigh	Queensland
Australia	Novartis Investigative Site	Bicton	Western Australia
Australia	Novartis Investigative Site	Brookvale	New South Wales
Australia	Novartis Investigative Site	Browns Plains	Queensland
Australia	Novartis Investigative Site	Castle Hill	New South Wales
Australia	Novartis Investigative Site	Chemside	Queensland
Australia	Novartis Investigative Site	Dandenong	Victoria
Australia	Novartis Investigative Site	Dapto	New South Wales
Australia	Novartis Investigative Site	Darlinghurst	New South Wales
Australia	Novartis Investigative Site	Daw Park	South Australia
Australia	Novartis Investigative Site	Deception Bay	Queensland
Australia	Novartis Investigative Site	East Fremantle	Western Australia
Australia	Novartis Investigative Site	East Victoria Park	Western Australia
Australia	Novartis Investigative Site	Ermington	New South Wales
Australia	Novartis Investigative Site	Everton Plaza	Queensland
Australia	Novartis Investigative Site	Fremantle	Western Australia
Australia	Novartis Investigative Site	Glenelg East	South Australia
Australia	Novartis Investigative Site	Golden Grove	South Australia
Australia	Novartis Investigative Site	Gosford	New South Wales
Australia	Novartis Investigative Site	Hamley Bridge	South Australia
Australia	Novartis Investigative Site	Hinchinbrook	New South Wales
Australia	Novartis Investigative Site	Holland Park	Queensland
Australia	Novartis Investigative Site	Jimboomba	Queensland
Australia	Novartis Investigative Site	Kedron	Queensland
Australia	Novartis Investigative Site	Kenmore	Queensland
Australia	Novartis Investigative Site	Kensington Gardens	South Australia
Australia	Novartis Investigative Site	Kingswood	New South Wales
Australia	Novartis Investigative Site	Kippa Ring	Queensland
Australia	Novartis Investigative Site	Lalor	Victoria
Australia	Novartis Investigative Site	Logan Central	Queensland
Australia	Novartis Investigative Site	Loganholme	Queensland
Australia	Novartis Investigative Site	Malvern	Victoria
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Mermaid Beach	Queensland
Australia	Novartis Investigative Site	Mirrabooka	Western Australia
Australia	Novartis Investigative Site	Morayfield	Queensland
Australia	Novartis Investigative Site	Morley	Western Australia
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Nerang	Queensland
Australia	Novartis Investigative Site	Noble Park	Victoria
Australia	Novartis Investigative Site	Noranda	Western Australia
Australia	Novartis Investigative Site	Oakleigh East	Victoria
Australia	Novartis Investigative Site	Perth	Western Australia
Australia	Novartis Investigative Site	Perth	Western Australia
Australia	Novartis Investigative Site	Perth	Western Australia
Australia	Novartis Investigative Site	Pinjarra	Western Australia
Australia	Novartis Investigative Site	Preston	Victoria
Australia	Novartis Investigative Site	Prospect	South Australia
Australia	Novartis Investigative Site	Rosebud	Victoria
Australia	Novartis Investigative Site	Spearwood	Western Australia
Australia	Novartis Investigative Site	Sydney	New South Wales
Australia	Novartis Investigative Site	Woodvale	Western Australia
Australia	Novartis Investigative Site	Woolloongabba	Queensland
Australia	Novartis Investigative Site	Yokine	Western Australia
New Zealand	Novartis Investigative Site	Auckland
New Zealand	Novartis Investigative Site	Auckland
New Zealand	Novartis Investigative Site	Christchurch
New Zealand	Novartis Investigative Site	Dunedin
New Zealand	Novartis Investigative Site	Grafton, Auckland
New Zealand	Novartis Investigative Site	Hamilton
New Zealand	Novartis Investigative Site	Tauranga
New Zealand	Novartis Investigative Site	Tauranga
New Zealand	Novartis Investigative Site	Wellington
New Zealand	Novartis Investigative Site	Wellington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Trough Forced Expiratory Volume in 1 Second (FEV1) (NVA237 Versus Tiotropium)	Spirometry was conducted according to internationally accepted standards. Trough FEV1 referred to the mean of FEV1 at 23:15 hours and 23:45 hours after the morning dose of study drug. The baseline was defined as the average of FEV1 values taken in the clinic 45 min and 15 min prior to the first dose of randomized treatment at Visit 3. A mixed model was used and contained treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilators, and FEV1 post-inhalation of bronchodilators and stratification factors as covariates. A positive change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Change From Baseline in Mean Trough FEV1 (Flu/Sal Versus NVA237/Tiotropium+Flu/Sal)	Spirometry was conducted according to internationally accepted standards. Trough FEV1 referred to the mean of FEV1 at 23:15h and 23:45h after the morning dose of study drug. The baseline was defined as the average of FEV1 values taken in the clinic 45min and 15min prior to the first dose of randomized treatment at Visit 3. A mixed model was used and contained treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilators, and FEV1 post-inhalation of bronchodilators and stratification factors as covariates. A positive change from baseline indicates improvement.	baseline, 4 weeks, 8 weeks, 12 weeks	No
Secondary	Change From Baseline in Mean Trough FEV1	Spirometry was conducted according to internationally accepted standards. Trough FEV1 referred to the mean of FEV1 at 23:15h and 23:45h after the morning dose of study drug. The baseline was defined as the average of FEV1 values taken in the clinic 45min and 15min prior to the first dose of randomized treatment at Visit 3. A mixed model was used and contained treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilators, and FEV1 post-inhalation of bronchodilators and stratification factors as covariates. A positive change from baseline indicates improvement.	baseline, 4 weeks, 8 weeks, 12 weeks	No
Secondary	Change From Baseline in Total Score of the St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) After 12 Weeks of Treatment	SGRQ-C is a health related quality of life questionnaire consisting of 40 items divided into two components: 1) symptoms, 2) activity& impacts. The lowest possible value is zero and the highest is 100. Higher values corresponded to greater impairment in quality of life. An analysis model included terms for treatment, baseline total SGRQ score, FEV1 and baseline smoking status. The model also contained as fixed effects the baseline total SGRQ score, FEV1 prior to inhalation of short acting bronchodilator, FEV1 post inhalation of short acting bronchodilator and stratification factors as covariates. A negative change from baseline indicates improvement.	12 weeks	No
Secondary	Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Use	The total number of puffs of rescue medication used over the last 12 h recorded in the morning (nighttime use) and in the evening (daytime use) over the full 12 weeks was divided by the total number of days with non-missing rescue data to derive the mean daytime and nighttime number of puffs of rescue medication. Change from baseline in the mean daytime and nighttime number of puffs of rescue medication was analyzed as for the change from baseline in the mean daily number of puffs of rescue medication.	baseline, 12 weeks	No
Secondary	Mean Percentage of Nights With 'no Nighttime Awakenings'	A night with 'no nighttime awakenings' is defined from diary data as any night where patient did not wake up due to symptoms. Total number of nights with 'no nighttime awakenings' over treatment period was divided by total number of nights where diary recordings have been made in order to derive percentage of 'no nighttime awakenings' which will be summarized by treatment and analyzed using a similar mixed model as specified for primary analysis. Diary data recorded during the 7 day run-in period was used to calculate baseline percentage of nights 'no nighttime awakenings'.	12 weeks	No
Secondary	Mean Percentage of Days With Performance of Usual Activities	A 'day able to perform usual daily activities' was defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The percentage of 'days able to perform usual daily activities' was derived and analyzed using a similar mixed model as specified for primary analysis as for the percentage of nights with 'no nighttime awakenings'.	12 weeks	No