Study of Efficacy and Safety of NVA237 in Patients With Poorly Controlled Asthma

April 10, 2015 updated by: Novartis Pharmaceuticals

A Randomized, Double-blind, Parallel Group, 52-week Study Evaluating the Efficacy, Safety and Tolerability of NVA237 in Patients With Poorly Controlled Asthma

The study will assess efficacy, safety and tolerability of NVA237 compared to placebo in patients with poorly controlled asthma over 52 weeks of treatment.

Study Overview

Status

Withdrawn

Conditions

Detailed Description

The study will assess efficacy and safety of NVA237 compared to placebo, in addition to background therapy with LABA/ICS in patients with poorly controlled asthma.

Study Type

Interventional

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Written informed consent must be obtained before any assessment is performed; Male and female adult patients aged 18 to <75 years; Patients with a diagnosis of asthma (according to GINA 2012) for a period of at least 5 years prior screening; The diagnosis of asthma must have been made before the patient was 40; Increase in forced expiratory volume in 1 second (FEV1) of ≥ 12% and ≥ 200 mLs within 30 minutes after administration of 400 µg salbutamol/360 µg albuterol (or equivalent dose); Pre-bronchodilator FEV1 of ≥ 50 and ≤ 80% of the predicted normal value for the patient; Patients who qualify for treatment (according to GINA 2012) and have been treated with a stable dose of a fixed dose inhaled corticosteriod (ICS) and long-acting β2 agonist (LABA) combination for at least 4 weeks prior to screening. Patient must be using a total daily dose of ICS of ≥800 μg/day of budesonide of equivalent; All patients must be symptomatic with a mean ACQ-5 score ≥ 1.5 at Visit 101 and Visit 102; A documented history of one or more asthma exacerbations in the previous 12 months that required either treatment with additional or increased dose of systemic corticosteroids for at least 3 days, or an emergency room visit, or hospital treatment, or intubation

Exclusion Criteria:

Contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class, or any component thereof:

Muscarinic antagonist agents, sympathomimetic amines, lactose or any of the other excipients of the study drug, long and short acting beta-2 agonists, corticosteroids; Women of child-bearing potential; Resting QTcF ≥ 450 ms (male) or ≥ 460 ms (female) at Visit 101 (assessed by central reader) and at Visit 102 (assessed by investigator at the site); Patients with a body mass index (BMI) of more than 40 kg/m2; Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction, arrhythmia, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment; Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention (BPH patients who are stable on treatment can be considered); Patients who have had an asthma exacerbation that required either treatment with additional or increased dose of systemic corticosteroids for at least 3 days, or an emergency room visit, or hospital treatment, or intubation in the 6 weeks prior to screening; Patients who have smoked or inhaled tobacco products within the 6 month period prior to screening, or who have a smoking history of greater than 10 pack years (Note:10 pack years = 1 pack /day x 10 yrs., or ½ pack/day x 20 yrs.); Patients with a history of chronic lung diseases other than asthma, including (but not limited to) chronic obstructive pulmonary disease, bronchiectasis, sarcoidosis, interstitial lung disease, cystic fibrosis, and tuberculosis (unless tuberculosis is confirmed as no longer active by imaging); Patients on Maintenance Immunotherapy (desensitization) for allergies must have been so for at least 3 months prior to run-in, and must be expected to remain unchanged throughout the course of the study;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NVA237
Participants will receive NVA237 once daily in addition to their background therapy during the 52- week treatment period. All participants will receive salbutamol/ albuterol as rescue medication.
NVA237 capsules for inhalation, delivered via Concept1 once daily
Taken as rescue medication
Placebo Comparator: Placebo
Participants will receive placebo to NVA237 in addition to their background therapy during the 52-week treatment period. All participants will receive salbutamol/ albuterol as rescue medication.
Taken as rescue medication
Placebo to NVA237 delivered via Concept1 once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 26
Time Frame: Week 26
Spirometry testing will be performed in accordance with American Thoracic Society standards. Trough FEV1 defined as the mean of two measurements at 23 hours 15 minutes and 23 hour 45 minutes post dosing.
Week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to First Moderate or Severe Asthma Exacerbation Over 52 Weeks of Treatment
Time Frame: 52 weeks
Asthma exacerbations are considered to be moderate if treatment with rescue systemic corticosteroids for greater than or equal to 3 days as outpatient or less than or equal to 24 hour emergency room visit was required. Asthma exacerbations are considered severe if treatment with rescue systemic corticosteroids for greater than or equal to 3 days and hospitalization or emergency department visit greater than 24 hours were required or death due to asthma. The time to the first moderate or severe asthma exacerbation is the study day on which the patient experienced first moderate or severe asthma exacerbation.
52 weeks
Asthma Control Questionnaire (ACQ-7) Overall Score at Week 26
Time Frame: Week 26
Asthma symptoms will be evaluated by the Asthma Control Questionnaire (ACQ-7). The ACQ has six questions to be answered by the patient, each with a 7 point scale (0-good control, 6-poor control), and one item where the actual pre-bronchodilator FEV1 value expressed in % of predicted FEV1. The overall score is an average of the 7 items.
Week 26
Quality of Life as Assessed by Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) Over 52-Week Treatment Period.
Time Frame: Week 12, Week 26, Week 52
There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental exposure). Each question will be answered on a 7 point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). The overall AQLQ score is the mean of all 32 responses, and the individual domain scores are the means of the items in those domains (a minimum domain / overall score of 1 = Severely impaired whereas a maximum domain / overall score of 7 = not impaired at all). A positive change from baseline score indicates improvement.
Week 12, Week 26, Week 52
Quality of Life Assessment With St. George's Respiratory Questionnaire (SGRQ) Over 52-Week Treatment Period
Time Frame: Week 12, Week 26, Week 52
SGRQ is a health related quality of life questionnaire consisting of 50 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.
Week 12, Week 26, Week 52
Shortened Version of the Asthma Control Questionnaire (ACQ-6)
Time Frame: Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
This shortened version of the asthma control questionnaire (symptoms plus β2-agonist) consists of 6 items (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheeze and rescue short-acting β2-agonist use) between 0 and 6 (0 = maximum control; 6 = no control ) and a total score is the mean of 6 items.
Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
Shortened Version of the Asthma Control Questionnaire (ACQ-5)
Time Frame: Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
This shortened version of the asthma control questionnaire (symptoms only) consists of 5 items (nighttime waking, symptoms on waking, activity limitation, shortness of breath, and wheeze) between 0 and 6 (0 = maximum control; 6 = no control) and a total score is the mean of 5 items.
Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
Peak Forced Expiratory Volume in 1 Second (FEV1) Over 52 Weeks of Treatment
Time Frame: Day 1, Week 4, Week 26, Week 52
Spirometry will be conducted according to internationally accepted standards. Peak FEV1= the maximum FEV1 recorded in the period between 0 minutes and 3 hours post dose.
Day 1, Week 4, Week 26, Week 52
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC0-3h) Over 52 Weeks of Treatment
Time Frame: Day 1, Week 4, Week 26, Week 52
FEV1 will be measured with spirometry conducted according to internationally accepted standards. Measurements will be made at 5, 15, and 30 minutes; and 1, 2, and 3 hours post-dose.
Day 1, Week 4, Week 26, Week 52
Predose Forced Expiratory Volume in 1 Second (FEV1) Over 52 Weeks of Treatment
Time Frame: Week 2, Week 4, Week 8, Week 26, Week 39, Week 52
FEV1 will be measured with spirometry conducted according to internationally accepted standards. Predose FEV1 defined as the mean of FEV1 at -45 minutes and -15 minutes before the morning dose.
Week 2, Week 4, Week 8, Week 26, Week 39, Week 52
Trough Forced Expiratory Volume in 1 Second (FEV1) Over 52 Weeks of Treatment
Time Frame: Day 2, Week 4, Week 26, Week 52
FEV1 will be measured with spirometry conducted according to internationally accepted standards. Trough FEV1 defined as the mean of FEV1 23 hours 15 minutes and the 23 hours 45 minutes post dose.
Day 2, Week 4, Week 26, Week 52
Mean Daily Number of Puffs of Rescue Medication Over 52 Weeks of Treatment
Time Frame: 52 Weeks
Participants will maintain a diary to record the number of puffs of rescue Short-acting B2 agonist (SABA) used in the previous 24 hours to treat asthma symptoms.
52 Weeks
Rate of Moderate or Severe Asthma Exacerbation
Time Frame: 52 Weeks
Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years
52 Weeks
Rate of Severe Asthma Exacerbation
Time Frame: 52 Weeks
Rate of severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years
52 Weeks
Time To First Severe Asthma Exacerbation
Time Frame: 52 Weeks
Asthma exacerbations are considered to be severe if treatment with rescue systemic corticosteroids for greater than or equal to 3 days and hospitalization or emergency department visit greater than 24 hours required or death due to asthma. The time to the first severe asthma exacerbation = the study day on which the patient experienced first severe asthma exacerbation.
52 Weeks
Time To First Asthma Exacerbation (Mild, Moderate, or Severe)
Time Frame: 52 Weeks
Asthma exacerbation are considered Mild if treatment with inhaled or nebulized Short-acting B2 agonist (SABA), increase in inhaled corticosteroid only, or requires less than 3 days of systemic corticosteroids. Asthma exacerbations are considered to be moderate if treatment with rescue systemic corticosteroids for greater than or equal to 3 days as outpatient or less than or equal to 24 hour emergency room visit required. Asthma exacerbations are considered severe if treatment with rescue systemic corticosteroids for greater than or equal to 3 days and hospitalization or emergency department visit greater than 24 hours required or death due to asthma. The time to the first mild, moderate, or severe asthma exacerbation = the study day on which the patient experienced first asthma exacerbation of any severity.
52 Weeks
Rate of Asthma Exacerbation (Mild, Moderate, or Severe)
Time Frame: 52 Weeks
Rate of mild, moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years
52 Weeks
Morning Daily Peak Expiratory Flow (PEF) Over 52 Weeks of Treatment
Time Frame: Every 3 Months, 52 Weeks
Peak Expiratory Flow (PEF) will be measured every morning within 15 minutes of waking and before dosing using a peak flow meter, and recorded in the patient diary.
Every 3 Months, 52 Weeks
Evening Daily Peak Expiratory Flow (PEF) Over 52 Weeks of Treatment
Time Frame: Every 3 Months, 52 Weeks
Peak Expiratory Flow (PEF) will be measured every evening using a peak flow meter, and recorded in the patient diary.
Every 3 Months, 52 Weeks
Asthma Control Diary (ACD) Symptom Score Over 52-Week Treatment Period
Time Frame: Every 3 Months, 52 Weeks
The mean symptom score for ACD is defined as the sum of daily symptom scores divided by number of days where diary records were made. The daily symptom score for ACD is defined as the mean of the responses to the 5 symptom questions for any day with ACD questions answered.
Every 3 Months, 52 Weeks
Lung Function Assessed by Forced Expiratory Volume for 1 Second (FEV1)
Time Frame: Week 1, Week 2, Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
FEV1 will be measured with spirometry conducted according to internationally accepted standards.
Week 1, Week 2, Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
Forced Vital Capacity (FVC)
Time Frame: Week 2, Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function.
Week 2, Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
Asthma Control Questionnaire (ACQ-7) Over 52 Weeks of Treatment
Time Frame: Week 4, Week 8, Week 12, Week 26, Week 39, Week 52
Asthma symptoms will be evaluated by the Asthma Control Questionnaire (ACQ). The ACQ has six questions to be answered by the patient, each with a 7 point scale (0-good control, 6-poor control), and one item where the actual pre-bronchodilator FEV1 value expressed in % of predicted FEV1. The overall score is an average of the 7 items.
Week 4, Week 8, Week 12, Week 26, Week 39, Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Anticipated)

May 1, 2017

Study Completion (Anticipated)

May 1, 2017

Study Registration Dates

First Submitted

April 29, 2014

First Submitted That Met QC Criteria

April 29, 2014

First Posted (Estimate)

May 1, 2014

Study Record Updates

Last Update Posted (Estimate)

April 13, 2015

Last Update Submitted That Met QC Criteria

April 10, 2015

Last Verified

April 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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