NVA237 Versus Placebo 12-week Efficacy Study

Phase 3

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: NVA237
Drug: Placebo

Registration Number: NCT01709864

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The study serves to determine whether the treatment of patients with stable, symptomatic Chronic Obstructive Pulmonary Disease (COPD) with the investigational drug NVA237 is efficient and safe. The efficacy and safety of the drug will be tested against a placebo treatment.

The primary criterion to assess efficacy will be the difference between the serial lung function measurements of patients who have been treated for 12 weeks with NVA237 versus those that have received placebo treatment for 12 weeks. A serial lung function measurement (FEV1 testing) will be conducted and the "area under the curve" will be the measure for the ability to breathe.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 440

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NVA237	NVA237	NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo	Placebo	Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing	12 weeks	The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit	Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough)	Trough Forced Expiratory Volume in one second (FEV1) is the mean of FEV1 at 23h 15min and 23h 45min after the morning dose of the previous day. Pre-dose trough FEV1 is the mean of FEV1 at -45min and -15min before morning dose
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)	Day 1 and Week 12 (Day 85)	The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various time points post dosing on day 1 and at week 12 to calculate the AUC for these different time spans.
Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire	Week 12	The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline).
Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12	Week 12	Breathlessness at week 12 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Patients are considered to have clinically significant improvement with the TDI score change versus BDI being equal to or greater than 1. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.
Percentage of Nights With "no Nighttime Awakenings"	from Baseline up to 12 weeks	Patients are reporting symptoms by using an electronic diary. A night with "no nighttime awakening" is defined from diary data as any night where the patient did not wake up due to symptoms. Percentage of no nighttime awakenings from Baseline up to 12 weeks.
Percentage of Participants With a Clinically Important Improvement of >=4units in the SGRQ Total Score at Week 12	Week 12	The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically significant improvement in SGRQ is defined as less than or equal to -4 change from baseline.
Percentage of "Days Able to Perform Usual Daily Activities"	from Baseline up to 12 weeks	Patients are reporting symptoms by using an electronic diary. 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.
Percentage of Days With "no Daytime Symptoms"	from Baseline up to 12 weeks	Patients are reporting symptoms by using an electronic diary. A day with "no daytime symptoms" is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours. The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100.
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)	Baseline, Day 1 and Week 12 (Day 85)	The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.
Change From Baseline of Daily Symptom Scores	12 weeks	Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am and each pm. Each question can be answered w/1 of 4 pre-defined answers, with a unit value of 0-3, 0 is least \& 3 is most severe symptom.Symptom scores are calculated as the mean of combined daily symptom scores(combined from am \& pm)for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. Patients may have met the min. response requirements for the night scores(am questions),but not for the day scores(pm questions)or vice versa, the # of patients analyzed can vary between both day \& night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day \& night scores.
Change From Baseline of Morning and Nighttime Symptom Scores at Week 12	12 weeks	Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am \& each pm.Each question can be answered w/1 of 4 pre-defined answers,with a unit value of 0-3, 0 is least \& 3 is most severe symptom.Symptom scores are calculated as the mean of the symptom scores(either the score assessed in am for the previous 12 hrs-referred to as nighttime scores,or the score assessed in pm for the previous 12 hrs-referred to as the daytime symptom score) for each patient over 12 weeks.The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. the # of patients analyzed can vary between both day \& night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day \& night scores.
Percentage of Days Without Rescue Medication Use	12 weeks	Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization.
The Average Number of Puffs of Rescue Medication Per Day	baseline and 12 weeks	Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the mean daily number of puffs used per patient over the 12 weeks treatment period.
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)	Baseline, Day 1 and Week 12 (Day 85)	The Forced Vital Capacity (FVC) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.