NVA237 BID Versus Placebo Twelve-week Efficacy Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01715298
First received: October 24, 2012
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: NVA237
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Standardized Area Under the Curve for Forced Expiratory Volume in one second post dosing [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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:
  • Standardized Area Under the Curve for Forced Expiratory Volume in one second post dosing [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 various time points post dosing at day 1 to calculate the AUC.

  • Standardized Area Under The Curve for Forced Expiratory Volume in one second for different time spans post dosing [ Time Frame: Day 1 and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in one second at all individual timepoints [ Time Frame: Day 1 and 12 weeks ] [ Designated as safety issue: No ]
    The Forced Expiratory Volume in one second assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.

  • Mean trough Forced Expiratory Volume in one second [ Time Frame: Day 1 and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Health status assessed by St. George's Respiratory Questionnaire [ Time Frame: Day 1 and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Breathlessness assessed by Transition Dyspnea Index [ Time Frame: Day 1 and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Mean number of puffs of rescue medication per day [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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. The baseline is calculated from the run-in epoch prior to randomization.

  • Percentage of days without rescue medication use [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Daily symptom scores [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Patients are reporting symptoms by using an electronic diary. Symptom scores are calculated as combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.

  • Percentage of nights with "no nighttime awakenings" [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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. The baseline is calculated from the run-in epoch prior to randomization

  • Percentage of days with "no daytime symptoms" [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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 baseline is calculated from the run-in epoch prior to randomization.

  • Percentage of "days able to perform usual daily activities" [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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. The baseline is calculated from the run-in epoch prior to randomization.

  • Safety and Tolerability [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    The safety and tolerability of NVA237 will be assessed with regard to vital signs, ECGs, laboratory evaluations and adverse events over the 12 week treatment.

  • Forced Vital Capacity at all individual timepoints [ Time Frame: Day 1 and 12 weeks ] [ Designated as safety issue: No ]
    The Forced Vital Capacity assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.

  • Mean trough Forced Vital Capacity [ Time Frame: Day 1 and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Morning symptom scores [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Patients are reporting morning symptoms by using an electronic diary. Morning symptoms scores for each patient over 12 weeks are reported. The baseline is calculated from the run-in epoch prior to randomization.

  • Evening symptom scores [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Patients are reporting evening symptoms by using an electronic diary. Evening symptoms scores for each patient over 12 weeks are reported. The baseline is calculated from the run-in epoch prior to randomization.


Enrollment: 432
Study Start Date: November 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NVA237
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Drug: NVA237
NVA237 (Glycopyrronioum bromide) as a powder for inhalation in single-dose capsules
Placebo Comparator: Placebo
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Drug: Placebo
Placebo powder for inhalation in single-dose capsules (matching those for NVA237).

  Eligibility

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

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01715298

  Show 59 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01715298     History of Changes
Other Study ID Numbers: CNVA237A2318
Study First Received: October 24, 2012
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Anticholinergic
Antimuscarinic
Chronic Obstructive Airway Disease
Chronic Obstructive Lung Disease
Chronic Obstructive Pulmonary Disease
COPD
LAMA
Lung Disease
Lung Diseases, Obstructive
Lung Function
Muscarinic receptor antagonist
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 24, 2014