Back to resultsBronchodilator Effects and Safety of Glycopyrronium Bromide (25 ug and 50 ug o.d.) in Asthma
Primary Purpose
Asthma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NVA237 (glycopyrronium bromide)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring asthma,, NVA237,, glycopyrronium bromide, allergic asthma,, allergy triggered asthma,, reactive asthma,, asthma attack,, difficulty breathing
Eligibility Criteria
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sarcoidosis, interstitial lung disease, cystic fibrosis, and tuberculosis (unless tuberculosis is confirmed as no longer active by imaging).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).
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Other
Other
Other
Other
Other
Other
Arm Label
1(NVA237 50 ug/NVA237 25 ug/placebo)
2(NVA237 50 ug/placebo/NVA237 25 ug)
3 (NVA237 25 ug/NVA237 50 ug/placebo)
4 (NVA237 25 ug/placebo/NVA237 50 ug)
5 (placebo/NVA237 50 ug/ NVA237 25 ug)
6 (placebo/ NVA237 25 ug/NVA237 50 ug)
Arm Description
Treatment sequence: NVA 237 50 ug, 25 ug and placebo
Treatment sequence: NVA 237 50 ug, placebo and 25 ug
Treatment sequence: NVA237 25 ug, 50 ug and placebo
Treatment sequence: NVA 237 25 ug, placebo and 50 ug
Treatment sequence: Placebo, NVA237 50 ug and 25 ug
Treatment sequence: placebo, NVA237 25 ug and 50 ug
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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)
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)
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)
Peak FEV1 During 4 Hours Post-dose After 1 Week of Treatment
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Peak FEV1 following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The peak effect following 1 week of treatment was defined as the maximum FEV1 during the first 4 hour on that day.
Trough Forced Vital Capacity (FVC) After 1 Week of Treatment
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of FVC following 1 week of treatment in respective treatment period. Trough Forced Vital Capacity (FVC) following 7 Days. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry
Percent Change From Baseline in FEV1/FVC Ratio
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of FEV1/FVC ratio following 1 week of treatment in respective treatment period
Mean Morning Peak Expiratory Flow (PEF) Following the 1-week Treatment Period
A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value
Mean Evening Peak Expiratory Flow Rate (PEF) Following 1-week Treatment
A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits. LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates
Mean Daily Number of Puffs of Rescue Medication During 1 Week of Treatment
A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. daytime and nighttime (combined) number of puffs is defined as the average of the respective number of puffs.
Full Information
NCT ID
NCT03137784
First Posted
April 24, 2017
Last Updated
January 15, 2019
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03137784
Brief Title
Bronchodilator Effects and Safety of Glycopyrronium Bromide (25 ug and 50 ug o.d.) in Asthma
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled 3-period Complete Cross-over Study to Assess the Bronchodilator Effects and Safety of Glycopyrronium Bromide (NVA237) (25 ug and 50 ug o.d.) in Asthma Patients.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
May 4, 2017 (Actual)
Primary Completion Date
December 29, 2017 (Actual)
Study Completion Date
December 29, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
asthma,, NVA237,, glycopyrronium bromide, allergic asthma,, allergy triggered asthma,, reactive asthma,, asthma attack,, difficulty breathing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
148 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1(NVA237 50 ug/NVA237 25 ug/placebo)
Arm Type
Other
Arm Description
Treatment sequence: NVA 237 50 ug, 25 ug and placebo
Arm Title
2(NVA237 50 ug/placebo/NVA237 25 ug)
Arm Type
Other
Arm Description
Treatment sequence: NVA 237 50 ug, placebo and 25 ug
Arm Title
3 (NVA237 25 ug/NVA237 50 ug/placebo)
Arm Type
Other
Arm Description
Treatment sequence: NVA237 25 ug, 50 ug and placebo
Arm Title
4 (NVA237 25 ug/placebo/NVA237 50 ug)
Arm Type
Other
Arm Description
Treatment sequence: NVA 237 25 ug, placebo and 50 ug
Arm Title
5 (placebo/NVA237 50 ug/ NVA237 25 ug)
Arm Type
Other
Arm Description
Treatment sequence: Placebo, NVA237 50 ug and 25 ug
Arm Title
6 (placebo/ NVA237 25 ug/NVA237 50 ug)
Arm Type
Other
Arm Description
Treatment sequence: placebo, NVA237 25 ug and 50 ug
Intervention Type
Drug
Intervention Name(s)
NVA237 (glycopyrronium bromide)
Intervention Description
In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
In each treatment arm, patient will receive placebo
Primary Outcome Measure Information:
Title
Trough FEV1 After One Week of Treatment, Point Estimate
Description
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 Outcome Measure Information:
Title
FEV1 AUC (5 Min-1 h) After One Week of Treatment
Description
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
Title
FEV1 AUC (5 Min-4 h) After One Week of Treatment
Description
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
Title
FEV1 AUC (5 Min - 23 h 45 Min) After One Week of Treatment
Description
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)
Time Frame
Following 1 week of treatment
Title
Peak FEV1 During 4 Hours Post-dose After 1 Week of Treatment
Description
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Peak FEV1 following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The peak effect following 1 week of treatment was defined as the maximum FEV1 during the first 4 hour on that day.
Time Frame
Following 1 week of treatment
Title
Trough Forced Vital Capacity (FVC) After 1 Week of Treatment
Description
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of FVC following 1 week of treatment in respective treatment period. Trough Forced Vital Capacity (FVC) following 7 Days. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry
Time Frame
Following 1 week of treatment
Title
Percent Change From Baseline in FEV1/FVC Ratio
Description
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of FEV1/FVC ratio following 1 week of treatment in respective treatment period
Time Frame
Following 1 week of treatment
Title
Mean Morning Peak Expiratory Flow (PEF) Following the 1-week Treatment Period
Description
A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value
Time Frame
Following 1 week of treatment
Title
Mean Evening Peak Expiratory Flow Rate (PEF) Following 1-week Treatment
Description
A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits. LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates
Time Frame
Following 1 week of treatment
Title
Mean Daily Number of Puffs of Rescue Medication During 1 Week of Treatment
Description
A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. daytime and nighttime (combined) number of puffs is defined as the average of the respective number of puffs.
Time Frame
Following 1 week of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Facility Information:
Facility Name
Novartis Investigative Site
City
North Dartmouth
State/Province
Massachusetts
ZIP/Postal Code
02747
Country
United States
Facility Name
Novartis Investigative Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Novartis Investigative Site
City
Skillman
State/Province
New Jersey
ZIP/Postal Code
08558
Country
United States
Facility Name
Novartis Investigative Site
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Novartis Investigative Site
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
Facility Name
Novartis Investigative Site
City
El Paso
State/Province
Texas
ZIP/Postal Code
79903
Country
United States
Facility Name
Novartis Investigative Site
City
Erpent
ZIP/Postal Code
5100
Country
Belgium
Facility Name
Novartis Investigative Site
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
Novartis Investigative Site
City
Mechelen
ZIP/Postal Code
2800
Country
Belgium
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10119
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Novartis Investigative Site
City
Grosshansdorf
ZIP/Postal Code
22927
Country
Germany
Facility Name
Novartis Investigative Site
City
Lubeck
ZIP/Postal Code
23552
Country
Germany
Facility Name
Novartis Investigative Site
City
Wiesbaden
ZIP/Postal Code
65187
Country
Germany
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
169-0073
Country
Japan
Facility Name
Novartis Investigative Site
City
Toshima-ku
State/Province
Tokyo
ZIP/Postal Code
171-0014
Country
Japan
Facility Name
Novartis Investigative Site
City
Daugavpils
State/Province
LVA
ZIP/Postal Code
LV-5417
Country
Latvia
Facility Name
Novartis Investigative Site
City
Riga
ZIP/Postal Code
LV 1002
Country
Latvia
Facility Name
Novartis Investigative Site
City
Riga
ZIP/Postal Code
LV-1038
Country
Latvia
Facility Name
Novartis Investigative Site
City
Klaipeda
ZIP/Postal Code
LT-92231
Country
Lithuania
Facility Name
Novartis Investigative Site
City
Klaipeda
ZIP/Postal Code
LT-92288
Country
Lithuania
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Bronchodilator Effects and Safety of Glycopyrronium Bromide (25 ug and 50 ug o.d.) in Asthma
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