NVA237 BID Versus Placebo Twelve-week Efficacy Study

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A 12-week Multi-center, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of NVA237 in Stable COPD Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01715298
• Other study ID #: CNVA237A2318
• Status: Completed
• Phase: Phase 3
• First received: October 24, 2012
• Last updated: March 9, 2015
• Start date: November 2012
• Est. completion date: December 2013

Study information

• Verified date: March 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 432
• 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: 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/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-defnied inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• NVA237
NVA237 (Glycopyrronioum bromide) as a powder for inhalation in single-dose capsules
• Placebo
Placebo powder for inhalation in single-dose capsules (matching those for NVA237).

Locations

Country	Name	City	State
United States	Novartis Investigative Site	*See Various Dept.'s*	Arizona
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Boulder	Colorado
United States	Novartis Investigative Site	Brooklyn	New York
United States	Novartis Investigative Site	Brooklyn	New York
United States	Novartis Investigative Site	Chandler	Arizona
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Cherry Hill	New Jersey
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Conyers	Georgia
United States	Novartis Investigative Site	Denton	Texas
United States	Novartis Investigative Site	East Providence	Rhode Island
United States	Novartis Investigative Site	Evansville	Indiana
United States	Novartis Investigative Site	Fall River	Massachusetts
United States	Novartis Investigative Site	Fort Mill	South Carolina
United States	Novartis Investigative Site	Fremont	Nebraska
United States	Novartis Investigative Site	Fresno	California
United States	Novartis Investigative Site	Fullerton	California
United States	Novartis Investigative Site	Great Neck	New York
United States	Novartis Investigative Site	Langhorne	Pennsylvania
United States	Novartis Investigative Site	Lexington	Kentucky
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Lynn Haven	Florida
United States	Novartis Investigative Site	Massapequa	New York
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Midvale	Utah
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	New Windsor	New York
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	North Dartmouth	Massachusetts
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Plymouth	Minnesota
United States	Novartis Investigative Site	Port Orange	Florida
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Pottstown	Pennsylvania
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	River Forest	Illinois
United States	Novartis Investigative Site	Rock Hll	South Carolina
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Skokie	Illinois
United States	Novartis Investigative Site	South Burlington	Vermont
United States	Novartis Investigative Site	St. Charles	Missouri
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Sunset	Louisiana
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Tipton	Pennsylvania
United States	Novartis Investigative Site	Wheat Ridge	Colorado
United States	Novartis Investigative Site	Winter Park	Florida
United States	Novartis Investigative Site	Yorba Linda	California
United States	Novartis Investigative Site	Yorba Linda	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing	The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.; The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur	Week 12	No
Secondary	Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing	The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is assessed at day 1 of treatment. Serial lung function measurements are taken at the following various time points post dosing at day 1 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.; .The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.	Day 1	No
Secondary	Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing	The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1FEV1) is assessed for different time spans (0-4 h, 4-8 h, 8-12 h) 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 the following time points post dosing on day 1 and at week 12 to calculate the FEV1 AUC for these different time spans: .5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.; The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 or week 12, respectively, (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.	Day 1 and Week 12	No
Secondary	Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints	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 points of the serial lung function measurements are 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The table indicates the percent change from baseline (CFB) in FEV1 and standard deviation in brackets. Where the FEV1 is lower than at baseline, a negative percent value can occur.	Day 1 and week 12	No
Secondary	Mean Trough Forced Expiratory Volume in One Second	Mean trough Forced Expiratory Volume in one second (FEV1) is assessed as the arithmetic mean of two FEV1 measurements, conducted within the last hour of a 24 hour period from a morning dose, either that of day 1 or at week 12 of treatment. The data is reported as the change from baseline (CFB), with the baseline being the arithmetic mean of the two pre-dose measurements (-45 min and -15 min) preceding the serial lung function measurements on Day 1	Day 1 and week 12	No
Secondary	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).	Week 12	No
Secondary	Breathlessness Assessed by Transition Dyspnea Index	Breathlessness at week 12 is measured using the interviewer-administered Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the interviewer-administered Baseline Dyspnea Index (BDI). The change from BDI to TDI is assessed, with the TDI total score ranging from -9 to +9 units of the scale. The lower the score, the more deterioration in severity of dyspnea. Patients are considered to have clinically significant improvement (MCID) with the TDI score change versus BDI being equal to or greater than 1.	Week 12	No
Secondary	Change From Baseline in Mean 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 change from baseline in the mean daily number of puffs used per patient over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization (mean number of puffs per day). A negative number indicates a reduction in the mean daily number of puffs of rescue medication.	Baseline and week 12	No
Secondary	Change From Baseline in the 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 change from baseline in the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated as the percentage of days without usage of rescue medication from during the the run-in epoch prior to randomization.	Baseline and week 12	No
Secondary	Change From Baseline in Daily Symptom Scores	Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Symptom scores are calculated as the mean of the combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The change from baseline in the least squares mean daily symptom scores over the 12 week treatment period is provided. Where the mean daily symptom score over the 12 week treatment period is lower than the baseline, the result is negative. A negative result indicates an improvement in COPD symptom severity.	day 1 to week 12	No
Secondary	Change From Baseline in the Percentage of Nights With "no Nighttime Awakenings"	Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the morning questionnaire relates to the number of awakenings due to COPD symptoms during the previous night. The answer with the lowest symptom score is "no waking due to symptoms." A night with "no nighttime awakening" is defined from diary data as any night where the patient did not wake up due to symptoms. The change from baseline in the percentage of nights with "no nighttime awakening" is calculated from the mean percentage of nights with this answer over the 12 week treatment period, with the baseline being The baseline is calculated from the run-in epoch prior to randomization.	Day 1 and week 12	No
Secondary	Change From Baseline in the Percentage of Days With "no Daytime Symptoms"	Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. 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 in the evening questionnaire. The change from baseline in the percentage of days with "no daytime symptoms" is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline being. The baseline is calculated from the run-in epoch prior to randomization.	Day 1 to week 12	No
Secondary	Change From Baseline in Percentage of "Days Able to Perform Usual Daily Activities"	Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the evening questionnaire relates to the impact of COPD symptoms on the performance of usual daily activities ("Did your respiratory symptoms stop you performing your usual daily activities today"). The answer with the lowest symptom score is "not at all." 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 change from baseline in the percentage of "days able to perform usual daily activities" is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline beingThe baseline is calculated from the run-in epoch prior to randomization.	Day 1 to week 12	No
Secondary	Change From Baseline in Forced Vital Capacity at All Individual Timepoints	The Forced Vital Capacity (FVC)assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed. Serial lung function measurements are taken at the following time points following dosing on Day 1 and at week 12: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. For week 12 (day 85), the pre-dose measurements (-45 min and -15 min) and the trough measurements (23:15 h and 23:45 h post-dose) are included. The endpoints are the change from baseline in FVC following the morning dose on Day 1 and at Week 12. Where the FVC at any one timepoint is smaller than at baseline, a negative value can occur.	Day 1 and week 12	No
Secondary	Change From Baseline in Mean Trough Forced Vital Capacity	Mean trough Forced Vital Capacity (FVC) is assessed as the arithmetic mean of two FVC measurements, conducted within the last hour of a 24 hours period from a morning dose, either that of day 1 or at week 12 of treatment (23:15 h and 23:45 h assessments). The endpoints are the change from baseline in trough FVC on Day 1 and at Week 12, with the mean of the -45 min and -15 min measurements on Day 1 as the baseline.	Day 1 and week 12	No
Secondary	Change From Baseline in Morning and Nighttime Symptom Scores	Patients are reporting morning and nighttime symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Morning and nighttime symptoms scores for each patient over 12 weeks are reported and analyzed. Symptom scores are calculated as the mean of the symptom scores (morning symptom scores or nighttime symptom scores, respectively) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The outcome is calculated as the change from baseline in the morning and nighttime symptom scores, respectively. A negative number indicates a reduction in the symptom severity and is owed to the calculation of the change from baseline.	Day 1 to week 12	No