NVA237 Versus Placebo 12-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: NCT01709864
• Other study ID #: CNVA237A2317
• Status: Completed
• Phase: Phase 3
• First received: October 16, 2012
• Last updated: February 12, 2015
• Start date: November 2012
• Est. completion date: October 2013

Study information

• Verified date: February 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: 440
• Est. completion date: October 2013
• Est. primary completion date: October 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/ 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.

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 (glycopyrronium 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	Amarillo	Texas
United States	Novartis Investigative Site	Arlington	Texas
United States	Novartis Investigative Site	Arlington	Texas
United States	Novartis Investigative Site	Beaumont	Texas
United States	Novartis Investigative Site	Brandon	Florida
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Defuniak Springs	Florida
United States	Novartis Investigative Site	Easley	South Carolina
United States	Novartis Investigative Site	Edgewater	Florida
United States	Novartis Investigative Site	Fort Lauderdale	Florida
United States	Novartis Investigative Site	Fountain Valley	California
United States	Novartis Investigative Site	Fullerton	California
United States	Novartis Investigative Site	Gaffney	South Carolina
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Hialeah	Florida
United States	Novartis Investigative Site	Homewood	Alabama
United States	Novartis Investigative Site	Huntsville	Texas
United States	Novartis Investigative Site	Jasper	Alabama
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Ninety Six	South Carolina
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Pompano Beach	Florida
United States	Novartis Investigative Site	Port Orange	Florida
United States	Novartis Investigative Site	Raleigh	North Carolina
United States	Novartis Investigative Site	Riverside	California
United States	Novartis Investigative Site	Rock Hll	South Carolina
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Sarasota	Florida
United States	Novartis Investigative Site	Seneca	South Carolina
United States	Novartis Investigative Site	Shelby	North Carolina
United States	Novartis Investigative Site	Simpsonville	South Carolina
United States	Novartis Investigative Site	South Miami	Florida
United States	Novartis Investigative Site	Spartanburg	South Carolina
United States	Novartis Investigative Site	Summerfield	Florida
United States	Novartis Investigative Site	Tamarac	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Union	South Carolina
United States	Novartis Investigative Site	Waco	Texas
United States	Novartis Investigative Site	Winter Park	Florida

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 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.	12 weeks	No
Secondary	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	Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough)	No
Secondary	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.	Day 1 and Week 12 (Day 85)	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	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.	Week 12	No
Secondary	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.	Week 12	No
Secondary	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.	12 weeks	No
Secondary	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.	12 weeks	No
Secondary	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.	from Baseline up to 12 weeks	No
Secondary	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.	from Baseline up to 12 weeks	No
Secondary	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.	from Baseline up to 12 weeks	No
Secondary	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.	baseline and 12 weeks	No
Secondary	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.	12 weeks	No
Secondary	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.	Baseline, Day 1 and Week 12 (Day 85)	No
Secondary	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.	Baseline, Day 1 and Week 12 (Day 85)	No