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

Purpose

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.

Condition	Intervention	Phase
Chronic Obstructive Pulmonary Disease	Drug: NVA237 50µg once daily Drug: Tiotropium 18µg once daily Drug: Placebo Drug: NVA237 placebo + Tiotropium placebo.	Phase 3

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

Resource links provided by NLM:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Albuterol Fluticasone propionate Salmeterol Fluticasone Salmeterol xinafoate Tiotropium bromide

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Mean trough forced expiratory volume in 1 second (FEV1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Spirometry is conducted according to internationally accepted standards. Trough FEV1 refers to the mean of FEV1 at 23:15 hours and 23:45 hours after the morning dose of study drug. The baseline is 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. Mixed model used will contain 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.

Secondary Outcome Measures:

Mean trough forced expiratory volume in 1 second (FEV1) [ Time Frame: Weeks 4 and 8 ] [ Designated as safety issue: No ]
Spirometry is conducted according to internationally accepted standards. Trough FEV1 refers to the mean of FEV1 at 23:15h and 23:45h after the morning dose of study drug. The baseline is 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. Mixed model used will contain 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.
Total score of the St George's Respiratory Questionnaire for COPD patients (SGRQ-C) After 12 weeks of treatment [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
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 100. Higher values correspond to greater impairment in quality of life. Model will include terms for treatment, baseline total SGRQ score, FEV1 and baseline smoking status. The model will also contain 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.
Daily rescue Medication Use (number of puffs) Over the study duration (Baseline to Week 12) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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 will be 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 will be analyzed as for the change from baseline in the mean daily number of puffs of rescue medication.
Percentage of nights with 'no nighttime awakenings' over 12 weeks (Baseline to Week 12) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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 will be 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 similar mixed model as specified for primary analysis. Diary data recorded during the 7 day run-in period will be used to calculate baseline percentage of nights 'no nighttime awakenings'.
Performance of usual activities [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
A 'day able to perform usual daily activities' is 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' will be derived and analyzed as for the percentage of nights with 'no nighttime awakenings'.
Adverse Events, Death, and Serious or Clinically Significant Adverse Events or Related Discontinuations [ Time Frame: 12 weeks and 30 day follow-up (for SAE - 7 days for AE) ] [ Designated as safety issue: Yes ]
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Estimated Enrollment:	600
Study Start Date:	April 2012
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: NVA237 50 µg once daily NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Fluticasone/Salmeterol). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus fluticasone / salmeterol 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all patients were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.	Drug: NVA237 50µg once daily NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) Drug: NVA237 placebo + Tiotropium placebo. Tiotropium 18 μg o.d. delivered via a proprietary inhalation device
Active Comparator: Tiotropium 18µg once daily Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Fluticasone/Salmeterol). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus fluticasone / salmeterol 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all patients were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.	Drug: Tiotropium 18µg once daily Tiotropium 18 μg o.d. delivered via a proprietary inhalation device Drug: NVA237 placebo + Tiotropium placebo. Tiotropium 18 μg o.d. delivered via a proprietary inhalation device
Placebo Comparator: Placebo Placebo (NVA237 placebo + Tiotropium placebo + Fluticasone/Salmeterol). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus fluticasone / salmeterol 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all patients were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.	Drug: Placebo NVA237 placebo + Tiotropium placebo. Drug: NVA237 placebo + Tiotropium placebo. Tiotropium 18 μg o.d. delivered via a proprietary inhalation device

Eligibility

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

Criteria

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 α-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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01513460

Contacts

Contact: Novartis Pharmaceuticals

+41 61 324 1111

Clinicaltrial.enquiries@novartis.com

Show 55 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01513460 History of Changes
Other Study ID Numbers:	CNVA237AAU01
Study First Received:	January 16, 2012
Last Updated:	March 6, 2013
Health Authority:	United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Novartis:

Chronic Obstructive Pulmonary Disease,
NVA 237,
glycopyrronium,
COPD

Additional relevant MeSH terms:

Lung Diseases, Obstructive
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Salmeterol
Albuterol
Fluticasone
Tiotropium
Fluticasone, salmeterol drug combination
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on June 17, 2013