Efficacy, Safety and Tolerability of NVA237 in Patients With Chronic Obstructive Pulmonary Disease - Full Text View

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:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease)

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Trough FEV1 following 12 weeks of treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Trough FEV1 after 12 weeks of treatment is defined as the mean of the post-dose 23 h 15 min and the 23 h 45 min FEV1 values. FEV1 is measured using central spirometry according to ATS/ERS standardization. The trough FEV1 will be analyzed using a MIXED model for the full analysis set population. The model will contain 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, baseline ICS use as covariates.

Secondary Outcome Measures:

The total score of the St George's Respiratory Questionnaire (SGRQ) [ Time Frame: Weeks 12 and 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 value is zero and the highest 100. Higher value corresponds to greater impairment in quality of life. The health- related quality of life will be measured using SGRQ, which will be completed by the patient at the investigator's site. Total SGRQ score after 12 and 26 weeks will be analyzed using the same MIXED model.
Breathlessness measured using the Transition Dyspnea Index (TDI) after 12 and 26 weeks treatment [ Time Frame: Baseline, Weeks 12 and 26 ] [ Designated as safety issue: No ]
Dyspnea will be measured at baseline using BDI and during the treatment period using TDI, which captures changes from baseline. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort, each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating 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: Over 26 weeks ] [ Designated as safety issue: No ]
Rescue medication a patient requires is recorded in the electronic diary between visits and in 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 will be analyzed.
24h trough FEV1 after 1 day and 26 weeks of treatment [ Time Frame: Day 2 and Week 26 ] [ Designated as safety issue: No ]
Trough FEV1 of 26 weeks of treatment is defined as the mean of the post-dose 23 h 15 min and the 23 h 45 min FEV1 values. This is measured using central spirometry according to ATS/ERS standardization. This will be analyzed using the same MIXED model as specified for the primary analysis.
FEV1 and FVC at other time points [ Time Frame: Day 1, Day 2, Weeks 5, 12, 26 and 27 ] [ Designated as safety issue: No ]
FEV1 and FVC will be measured 45min, 15min pre-dose and some points up to 4h post dose at day 1, week 5, week 12 and week 26, will also be measured 23h15min and 23h45min post dose at day 2, week 12 and week 27, using central spirometry according to ATS/ERS standardization. This will be analyzed using the same MIXED model as specified for the primary analysis.
Peak FEV1 defined as the maximum FEV1 0-4 h post-dose in a subset of approximately 156 patients (approximately 104 NVA237: 52 placebo) [ Time Frame: Day 1, Weeks 12 and 26 ] [ Designated as safety issue: No ]
Peak FEV1 will be measured 45min, 15min pre-dose and some points up to 4h post dose at day 1, week 12 and week 26, using central spirometry according to ATS/ERS standardization. This will be analyzed using the same MIXED model as specified for the primary analysis.
Standardized FEV1 AUC(5 min-4 h) post-dose [ Time Frame: Day 1, Weeks 12 and 26 ] [ Designated as safety issue: No ]
The standardized (with respect to time) AUC for FEV1 will be calculated between 5 min and 4h post morning dose at day 1, week 12 and week 26 for all patients in the FAS population in the serial spirometry subgroup. The AUC (5 min-4 h) for FEV1 at each visit will be analyzed using the same MIXED model as specified for the primary analysis.
Other COPD symptoms (cough, wheezing, shortness or breath, sputum volume, sputum color and night time awakenings) collected via patient diary [ Time Frame: Over 26 weeks ] [ Designated as safety issue: No ]
Morning and evening daily clinical symptoms will be recorded in electronic diary, and will be analyzed using MIXED model.
Time to first COPD exacerbation [ Time Frame: Over 26 weeks ] [ Designated as safety issue: No ]
A COPD exacerbation is 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 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 are recorded in patient diary and other source documents.
COPD exacerbation rate [ Time Frame: Over 26 weeks ] [ Designated as safety issue: No ]
COPD exacerbations are recorded in patient diary and other source documents. The rate of COPD exacerbations during the 26 week treatment period will be analyzed using a generalized linear model assuming a negative binomial distribution.
Safety and Tolerability over 26 weeks [ Time Frame: Over 26 weeks ] [ Designated as safety issue: Yes ]
Vital signs, physical examination, ECGs, laboratory evaluations and adverse events will be performed at respective site visits.

Estimated Enrollment:	450
Study Start Date:	March 2012
Estimated Study Completion Date:	June 2013
Estimated 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

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

Contacts

Contact: Novartis Pharmaceuticals	+41613241111
Contact: Novartis Pharmaceuticals

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Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

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:	March 26, 2013
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 June 13, 2013

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