NCT03137784 - Bronchodilator Effects and Safety of Glycopyrronium Bromide (25 ug and 50 ug o.d.) in Asthma | Crick

Overview

The purpose of this trial is to characterize the bronchodilator effects and safety of 25 ug and 50 ug o.d. NVA237 (glycopyrronium bromide) doses compared to placebo in asthma patients

This study uses a randomized, double-blind, placebo controlled, 3-period cross-over clinical trial design. During a screening epoch patient eligibility will be assessed. The screening epoch will be followed by a 21-day Run-in epoch during which patients will continue their inhaled corticosteroids use but be withdrawn from LABA-treatment and switched to short-acting bronchodilator-rescue medication. After the Run-in period patients will be randomized to one of the 6 treatment sequences and enter the first 7-day study treatment period. Treatment period one is followed by a 10 to 14 days washout period after which patients begin the second 7-day treatment period which is then followed by a second 10 to 14 days washout period followed by the third 7-day treatment period. At the end of each treatment period spirometry will be performed to assess the primary endpoint in terms of trough FEV1. The study population will consist of approximately 144 patients with asthma who have been treated in a stable regimen of ICS/LABA for at least 4 weeks prior to screening.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

148

Conditions

Asthma

Interventions

NVA237 (glycopyrronium bromide)DRUG

In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose

PlaceboDRUG

In each treatment arm, patient will receive placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male and female adult patients aged \>= 18 or =\< 65 years * Patients with a diagnosis of asthma for a period of at least 1 year receiving daily treatment of ICS/LABA in a stable regimen for \>= 4 weeks * Pre-bronchodilator FEV1 of \>= 50% and =\< 80% of the predicted normal value and an increase in FEV1 of 12% and \>= 200 ml during reversibility testing Key Exclusion Criteria: * Patients who have had an asthma exacerbation that required either treatment with systemic corticosteroids for at least 3 days, or an emergency room visit, or hospital treatment within 6 weeks prior to screening and patients with a history of life-threatening asthma attacks * Patients who have had a respiratory tract infection within 4 weeks prior to screening. * Patients who have smoked or inhaled tobacco products within the past 6 month of screening. * 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 for at least 3 months prior to Run-in who are expected to change therapy throughout the course of the study. * Patients who during the Run-in period are shown to be intolerable to LABA withdrawal. * Patients who have discontinued LAMA therapy in the past (e.g. due to intolerance or perceived lack of efficacy).

Locations (21)

Novartis Investigative Site

North Dartmouth, Massachusetts, United States

Novartis Investigative Site

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Trough FEV1 After One Week of Treatment, Point Estimate

To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared to placebo in terms of trough FEV1 (mean of 23h 15 min and 23 h 45 min post -dose) following 1 week of treatment in the respective treatment period. Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 15 min and 23h 45 min post dose.

Time frame: Following 1 week of treatment

Secondary Outcomes

FEV1 AUC (5 Min-1 h) After One Week of Treatment

To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 5min-1h)

Time frame: Following 1 week of treatment

FEV1 AUC (5 Min-4 h) After One Week of Treatment

To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 5min-4h)

Time frame: Following 1 week of treatment

FEV1 AUC (5 Min - 23 h 45 Min) After One Week of Treatment

To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day AUC (5 min - 23 h 45 min)