Ignite Creation Date:
2025-12-25 @ 2:28 AM
Ignite Modification Date:
2026-03-05 @ 3:42 PM
Study NCT ID:
NCT03645434
Status:
COMPLETED
Last Update Posted:
2020-12-17
First Post:
2018-08-09
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Single Inhalation Dose Study to Assess Efficacy, Pharmacokinetics (PK), Safety and Tolerability of AZD8871 in Patients With Long-term Lung Diseases.
Sponsor:
AstraZeneca
Organization:
Study Overview
Official Title:
A Phase IIa, Randomised, Multi-centre, Double-blind, Placebo and Active-controlled, 3 Periods, Crossover Study to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of Inhaled AZD8871 Administered Once Daily for 2 Weeks in Patients With Moderate to Severe COPD
Status:
COMPLETED
Status Verified Date:
2020-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the efficacy and safety data of AZD8871 in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This study will determine the 24-hour efficacy (lung function) profile of AZD8871 600 μg relative to placebo dry powder inhaler (DPI) based on trough forced expiratory volume in 1 second (FEV1) following repeated dosing (2 weeks). Anoro® Ellipta® (umeclidinium/vilanterol) once daily is included as an active control. This study aims at providing a novel approach to the treatment of COPD with greater efficacy than single-mechanism bronchodilators, equivalent to long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) administered as free- or fixed-dose combination therapies, with an equivalent or superior safety and tolerability profile.
Detailed Description:
This randomized, double-blind, placebo and active-controlled crossover study will be conducted at 5 sites in Germany and the United Kingdom (UK). Approximately 180 patients will be screened in order to randomize 72 patients into the study. Based on previous studies estimate, it is anticipated that 54 patients will be evaluable (study completers) assuming an approximate 25% dropout rate. A subset of 36 patients, who will have specifically consented for pharmacokinetics (PK), will undergo PK assessments. The study will consist of -
* A Screening period: Will last up to 28 days and consists of 2 Screening visits (Visit 1 and Visit 2) and a run-in period (between a minimum of 14 and a maximum of 28 days; from Visit 2 to Visit 3).
* Three treatment periods (Visit 3; 14 days each; each separated by a wash-out period of 42 to 49 days) and
* A Follow-up Visit: 42 days (up to 49 days) after last investigational product (IP) administration.
Patients will be requested to stop their usual COPD therapy after signing the informed consent form (ICF) at Visit 1 and will be maintained on a mono-component inhaled corticosteroid (ICS) therapy, if required. Patients that were taking any LAMA will be maintained with ipratropium (34 µg × 2 puffs 4 times per day) between Visit 1 and Visit 2. In addition, salbutamol 100 µg will be provided as rescue medication during the study as needed (rescue medication has to be discontinued 6 hours before any pulmonary function test). Visit 1 and Visit 2 could be performed on the same day if no wash-out of prior medication is required and the patient visits the site in fasting condition. In case any wash-out of prior medication is required, then Visit 2 will be performed after the wash-out is complete. If reversibility criteria and forced expiratory volume in 1 second (FEV1) predicted values are fulfilled according to inclusion criteria, the patient will be started on run-in period to assess clinical stability. If reversibility criteria or FEV1 predicted values are not met, pulmonary function tests could be rescheduled at the latest, up to Day 14. During the run in period, all patients will receive ipratropium 34 µg × 2 puffs 4 times per day (must be discontinued 8 hours prior to previous any pulmonary function test). A paper diary will be used to collect adverse events (AEs) and concomitant medication during run-in and wash-out periods.
Eligible patients will be randomized in 1:1:1:1:1:1 ratio to 1 of 6 treatment sequences and will receive orally 1 of the following 3 treatments sequence in the form of inhalation powder using DPI :
* AZD8871 600 µg once daily (double-blind).
* Anoro® Ellipta® (55 µg umeclidinium \[UMEC\]/ 22 µg vilanterol \[VI\]) once daily (double-blind).
* Placebo (double-blind). Study treatment administration during all the visits at the sites (Day 1, Day 2, Day 8, and Day 14 of each treatment period) will be supervised by study personnel.
During the treatment period Visits, safety and tolerability assessments and pulmonary function measurements will be taken pre-dose and up to 24 hours (Day 1) and up to 4 hours (Day 8) post-dose, respectively.
At Visits 3 to 11, a subset of 36 patients will undergo PK assessments. Blood samples will be collected pre-dose and up to 24 hours post dose.
In follow-up visit, AEs, safety laboratory, electrocardiogram (ECG), vital signs and physical examination will be assessed.
The study includes 12 visits and the entire study period is scheduled to take from a minimum of 6.5 months (182 days) to a maximum of 7.5 months (217 days) for each individual patient. The estimated study duration is 12 months.
* A Screening period: Will last up to 28 days and consists of 2 Screening visits (Visit 1 and Visit 2) and a run-in period (between a minimum of 14 and a maximum of 28 days; from Visit 2 to Visit 3).
* Three treatment periods (Visit 3; 14 days each; each separated by a wash-out period of 42 to 49 days) and
* A Follow-up Visit: 42 days (up to 49 days) after last investigational product (IP) administration.
Patients will be requested to stop their usual COPD therapy after signing the informed consent form (ICF) at Visit 1 and will be maintained on a mono-component inhaled corticosteroid (ICS) therapy, if required. Patients that were taking any LAMA will be maintained with ipratropium (34 µg × 2 puffs 4 times per day) between Visit 1 and Visit 2. In addition, salbutamol 100 µg will be provided as rescue medication during the study as needed (rescue medication has to be discontinued 6 hours before any pulmonary function test). Visit 1 and Visit 2 could be performed on the same day if no wash-out of prior medication is required and the patient visits the site in fasting condition. In case any wash-out of prior medication is required, then Visit 2 will be performed after the wash-out is complete. If reversibility criteria and forced expiratory volume in 1 second (FEV1) predicted values are fulfilled according to inclusion criteria, the patient will be started on run-in period to assess clinical stability. If reversibility criteria or FEV1 predicted values are not met, pulmonary function tests could be rescheduled at the latest, up to Day 14. During the run in period, all patients will receive ipratropium 34 µg × 2 puffs 4 times per day (must be discontinued 8 hours prior to previous any pulmonary function test). A paper diary will be used to collect adverse events (AEs) and concomitant medication during run-in and wash-out periods.
Eligible patients will be randomized in 1:1:1:1:1:1 ratio to 1 of 6 treatment sequences and will receive orally 1 of the following 3 treatments sequence in the form of inhalation powder using DPI :
* AZD8871 600 µg once daily (double-blind).
* Anoro® Ellipta® (55 µg umeclidinium \[UMEC\]/ 22 µg vilanterol \[VI\]) once daily (double-blind).
* Placebo (double-blind). Study treatment administration during all the visits at the sites (Day 1, Day 2, Day 8, and Day 14 of each treatment period) will be supervised by study personnel.
During the treatment period Visits, safety and tolerability assessments and pulmonary function measurements will be taken pre-dose and up to 24 hours (Day 1) and up to 4 hours (Day 8) post-dose, respectively.
At Visits 3 to 11, a subset of 36 patients will undergo PK assessments. Blood samples will be collected pre-dose and up to 24 hours post dose.
In follow-up visit, AEs, safety laboratory, electrocardiogram (ECG), vital signs and physical examination will be assessed.
The study includes 12 visits and the entire study period is scheduled to take from a minimum of 6.5 months (182 days) to a maximum of 7.5 months (217 days) for each individual patient. The estimated study duration is 12 months.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: