NVA237 Versus Placebo 12-week Efficacy Study

Novartis Pharmaceuticals440 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

440

Conditions

Chronic Obstructive Pulmonary Disease

Interventions

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Patients with stable, symptomatic Chronic Obstructive Pulmonary Disease (COPD) with airflow obstruction of level 2 and 3 according to the current Global initiative for chronic Obstructive Lung Disease (GOLD) strategy (2011). 2. Patients with Forced Expiratory Volume in one second (FEV1) ≥ 30% and \<80 % of the predicted normal, and FEV1/ Forced Vital Capacity (FVC) \< 0.70 when measured 45 min after the inhalation of 84 µg ipratropium bromide. 3. Current or ex-smokers with at least 10 cigarette pack years smoking history. Exclusion criteria: 1. Patients with a history of long QT syndrome, with a prolonged QTc measured during screening, or patients who have a clinically significant ECG abnormality at screening. 2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 3. Pregnant or nursing (lactating) women. Women of childbearing potential unless using an effective method of contraception. 4. Patients who in the judgment of the investigator, would be at potential risk if enrolled into the study. 5. Patients who have a clinically significant concomitant disease at screening, including but not limited to clinically significant laboratory abnormalities, clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities, or with uncontrolled diabetes, which could interfere with the assessment of the efficacy and safety of the study treatment. 6. Patients with a body mass index (BMI) of more than 40 kg/m2. 7. Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to anticholinergic agents, long and short acting beta-2 agonists, or sympathomimetic amines. 8. Patients with any history of asthma, with onset of symptoms prior to age 40 years, or patients with a high blood eosinophil count during screening. Other protocol-defined inclusion/exclusion criteria may apply.

Locations (54)

Novartis Investigative Site

Homewood, Alabama, United States

Novartis Investigative Site

Jasper, Alabama, United States

Novartis Investigative Site

*See Various Dept.'s*, Arizona, United States

Novartis Investigative Site

Tucson, Arizona, United States

Novartis Investigative Site

Fountain Valley, California, United States

Outcomes

Primary Outcomes

Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing

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.

Time frame: 12 weeks

Secondary Outcomes

Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit

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

Time frame: Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough)

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)

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.

Time frame: Day 1 and Week 12 (Day 85)

Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire

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).

Time frame: Week 12

Percentage of Participants With a Clinically Important Improvement of >=4units in the SGRQ Total Score at 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.

Time frame: Week 12

Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at 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.

Time frame: Week 12

Change From Baseline of Daily Symptom Scores

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.

Time frame: 12 weeks

Change From Baseline of Morning and Nighttime Symptom Scores at Week 12

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.

Time frame: 12 weeks

Percentage of Nights With "no Nighttime Awakenings"

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.

Time frame: from Baseline up to 12 weeks

Percentage of Days With "no Daytime Symptoms"

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.

Time frame: from Baseline up to 12 weeks

Percentage of "Days Able to Perform Usual Daily Activities"

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.

Time frame: from Baseline up to 12 weeks

The Average Number of Puffs of Rescue Medication Per Day

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.

Time frame: baseline and 12 weeks

Percentage of Days Without Rescue Medication Use

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.

Time frame: 12 weeks

Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at 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.

Time frame: Baseline, Day 1 and Week 12 (Day 85)

Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at 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.

Time frame: Baseline, Day 1 and Week 12 (Day 85)