Chronic Obstructive Pulmonary Disease, COPD
Conditions
Keywords
COPD, Chronic obstructive pulmonary disease
Brief summary
This study in Chronic Obstructive Pulmonary Disease (COPD) patients will investigate the bronchodilatory effect of AZD8683. AZD8683 will be tested versus placebo and an active comparator.
Detailed description
A randomised, double-blind placebo- and active-controlled, multi-centre, 6-way cross-over, single-dose phase IIa study to investigate the bronchodilatory and systemic effects of 4 different doses of inhaled AZD8683 in patients with Chronic Obstructive Pulmonary Disease (COPD).
Interventions
DRUGAZD8683
AZD8683 administered via inhalation
DRUGPlacebo
Placebo administered via inhalation
DRUGTiotropium
Tiotropium administered via inhalation
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures Male or female, age ≥ 40 years at Visit 1. Women must be of non-childbearing potential or must have been stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 and be willing to continue until follow-up * Clinical diagnosis of COPD for more than 1 year at Visit 1 * FEV1 ≥ 30 to \< 80% of the predicted normal value (post-bronchodilator) at Visit 2 and post-bronchodilator FEV1/FVC \< 70% * Reversible airway obstruction
Exclusion criteria
* Significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the result of the study, or the patient's ability to participate in the study. * An exacerbation of COPD (defined as use of oral/parenteral glucocorticosteroids (GCS) and/or antibiotics and/or hospitalisation related to COPD) within 6 weeks of Visit 1or during the enrolment period * Treatment with systemic GCS within 6 weeks of Visit 2 or during the enrolment period * Respiratory tract infection of clinical relevance within 30 days of Visit 4, as judged by the Investigator * Long-term oxygen therapy, as judged by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peak FEV1 (0-24h) | The first 24 hours following dose administration | The maximum value over 24 hours post-dose, as change from baseline |
| Change From Baseline in Trough FEV1 (22-26h) | 22 to 26 hours following dose administration | The average over 22 to 26 hours, as change from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Increase in Diastolic Blood Pressure [DBP] | The first 24 hours following dose administration | Maximum (post-dose values - baseline value) for each treatment visit. |
| Maximum Increase Heart Rate [HR] | baseline, 24hr post dose | Maximum (post-dose values - baseline value) for each treatment visit. |
| Average FEV1 as a Change From Baseline | The first 24 hours following dose administration | Average FEV1 (0-24h): The average over 0 to 24 hours |
| PK Parameters (AZD8683) | Pre-dose, 24hr post-dose | Cmax, tmax, AUC |
| Maximum Increase in QTcF | baseline, 24hr post dose | maximum (post-dose values - baseline value) for each treatment visit. |
| Maximum Increase in Systolic Blood Pressure [SBP] | baseline, 24hr post dose | Maximum (post-dose values - baseline value) for each treatment visit. |
Countries
Poland, Sweden
Participant flow
Recruitment details
A total of 14 subjects were enrolled. Of these, 3 subjects were randomized to receive a treatment sequence consisting of 6 different treatments in random order. The study was terminated prematurely, hence only one period out of six planned was performed.
Participants by arm
| Arm | Count |
|---|---|
| Total Baseline All Patients population | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal due to study termination. | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Total Baseline |
|---|---|
| Age, Customized <=18 year | 0 participants |
| Age, Customized >=65 years | 1 participants |
| Age, Customized Between 18 and 65 years | 2 participants |
| Race/Ethnicity, Customized other | 0 Participants |
| Race/Ethnicity, Customized White | 3 Participants |
| Sex/Gender, Customized Female | 1 participants |
| Sex/Gender, Customized Male | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 0 | 0 / 0 | 1 / 1 | 0 / 0 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 | 0 / 0 | 0 / 1 | 0 / 0 | 0 / 1 |
Outcome results
Primary
Change From Baseline in Peak FEV1 (0-24h)
The maximum value over 24 hours post-dose, as change from baseline
Time frame: The first 24 hours following dose administration
Population: As the study was terminated prematurely none of the randomised patients have been analysed.
Primary
Change From Baseline in Trough FEV1 (22-26h)
The average over 22 to 26 hours, as change from baseline
Time frame: 22 to 26 hours following dose administration
Population: As the study was terminated prematurely none of the randomized patients have been analysed.
Secondary
Average FEV1 as a Change From Baseline
Average FEV1 (0-24h): The average over 0 to 24 hours
Time frame: The first 24 hours following dose administration
Population: As the study was terminated prematurely none of the randomized patients have been analysed.
Secondary
Maximum Increase Heart Rate [HR]
Maximum (post-dose values - baseline value) for each treatment visit.
Time frame: baseline, 24hr post dose
Population: As the study was terminated prematurely none of the randomised patients have bean analysed.
Secondary
Maximum Increase in Diastolic Blood Pressure [DBP]
Maximum (post-dose values - baseline value) for each treatment visit.
Time frame: The first 24 hours following dose administration
Population: As the study was terminated prematurely none of the randomised patients have bean analysed.
Secondary
Maximum Increase in QTcF
maximum (post-dose values - baseline value) for each treatment visit.
Time frame: baseline, 24hr post dose
Population: As the study was terminated prematurely none of the randomised patients have bean analysed.
Secondary
Maximum Increase in Systolic Blood Pressure [SBP]
Maximum (post-dose values - baseline value) for each treatment visit.
Time frame: baseline, 24hr post dose
Population: As the study was terminated prematurely none of the randomised patients have bean analysed.
Secondary
PK Parameters (AZD8683)
Cmax, tmax, AUC
Time frame: Pre-dose, 24hr post-dose
Population: As the study was terminated prematurely none of the randomised patients have bean analysed.