COPD, Healthy Subjects
Conditions
Keywords
Phase 1,, Safety,, Tolerability,, Healthy,, COPD patients
Brief summary
This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD7624 in healthy subjects and patients with chronic obstructive pulmonary disease.
Detailed description
A Phase I, Randomized, DoubleBlind Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Inhaled Doses (MAD) of AZD7624 to Healthy Subjects and Patients with COPD
Interventions
DRUGAZD7624
Multiple ascending doses (starting from 300 µg lung deposited dose up to 1200 µg) inhaled IMP via a nebulizer
DRUGPlacebo to match
Multiple doses inhaled placebo via a nebulizer
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture. * Provision of signed and dated, written informed consent prior to any study specific procedures * Plasma myoglobin and CK not above the upper reference range of the analysing laboratory at Day -1 * Male and/or female patients with COPD aged above18 years with suitable veins for cannulation or repeated venipuncture. * Clinical diagnosis of COPD for more than 1 year at Visit 1, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines
Exclusion criteria
* Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the IP * Receipt of another new chemical entity (defined as a compound which has not been approved for marketing) or participation in any other clinical study that included drug treatment within at least 3 months of the first administration of the IP in this study * Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results as judged by the Investigator * Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) * History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Up to 24 days | Summary of number of subjects who had at least one adverse event in any category (Safety analysis set) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Pharmacokinetic Parameters (AUC(0-tau) ) | PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3. | Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. \*AUC(0-tau) = AUC(0-last) where for cohorts 2,3,4,5 and 6 tau=24 hours and for cohort 1, tau=12 hours . Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken. |
| Summary of Pharmacokinetic Parameters (Cmax) | PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3. | Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken. |
| Summary of Pharmacokinetic Parameters (Cmin) | PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3. | Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken. |
Countries
United Kingdom
Participant flow
Recruitment details
Both the lung deposited doses and total delivered doses are reported in clinical study report, and the conversion is: In cohort 1 to 6, the lung deposited doses 151 µg, 303 µg, 595 µg, 1191 µg, 1160 µg and 580 µg are equivalent to the delivered doses 261µg, 522µg, 1027µg, 2053µg, 1932µg and 966µg, respectively.
Pre-assignment details
The screening period for all the subjects was from Day -42 to Day -2. Admission on day -1. A 8 to 9 days treatment period, 7 to 9 days follow up period. It was planned to enrol to 32 healthy volunteers and 20 COPD to the study, but 4 COPD patients (Due to stopping cohort 4 prematurly) and one healthy volunteer (in cohort 3) were not enrolled.
Participants by arm
| Arm | Count |
|---|---|
| AZD7624 Healthy Volunteers Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily | 23 |
| Placebo Healthy Volunteers Healthy Volunteers with Placebo, once daily or twice daily | 8 |
| AZD7624 COPD COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily | 11 |
| Placebo COPD COPD Patients with Placebo, once daily | 5 |
| Total | 47 |
Baseline characteristics
| Characteristic | AZD7624 Healthy Volunteers | Placebo Healthy Volunteers | AZD7624 COPD | Placebo COPD | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36 Years STANDARD_DEVIATION 9.7 | 32 Years STANDARD_DEVIATION 9.1 | 65 Years STANDARD_DEVIATION 9.7 | 65 Years STANDARD_DEVIATION 8.7 | 45.3 Years STANDARD_DEVIATION 17.1 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 23 Participants | 8 Participants | 10 Participants | 3 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 23 | 3 / 8 | 7 / 11 | 2 / 5 |
| serious Total, serious adverse events | 0 / 23 | 0 / 8 | 0 / 11 | 0 / 5 |
Outcome results
Primary
Adverse Events
Summary of number of subjects who had at least one adverse event in any category (Safety analysis set)
Time frame: Up to 24 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD7624 Healthy Volunteers | Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| AZD7624 Healthy Volunteers | Adverse Events | Any AE leading to discontinuation | 0 Participants |
| AZD7624 Healthy Volunteers | Adverse Events | Any Adverse Event (AE) | 6 Participants |
| AZD7624 Healthy Volunteers | Adverse Events | Any AE with outcome = death | 0 Participants |
| Placebo Healthy Volunteers | Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Placebo Healthy Volunteers | Adverse Events | Any AE with outcome = death | 0 Participants |
| Placebo Healthy Volunteers | Adverse Events | Any Adverse Event (AE) | 3 Participants |
| Placebo Healthy Volunteers | Adverse Events | Any AE leading to discontinuation | 1 Participants |
| AZD7624 COPD | Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| AZD7624 COPD | Adverse Events | Any Adverse Event (AE) | 7 Participants |
| AZD7624 COPD | Adverse Events | Any AE with outcome = death | 0 Participants |
| AZD7624 COPD | Adverse Events | Any AE leading to discontinuation | 2 Participants |
| Placebo COPD | Adverse Events | Any Adverse Event (AE) | 2 Participants |
| Placebo COPD | Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Placebo COPD | Adverse Events | Any AE leading to discontinuation | 0 Participants |
| Placebo COPD | Adverse Events | Any AE with outcome = death | 0 Participants |
Secondary
Summary of Pharmacokinetic Parameters (AUC(0-tau) )
Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. \*AUC(0-tau) = AUC(0-last) where for cohorts 2,3,4,5 and 6 tau=24 hours and for cohort 1, tau=12 hours . Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken.
Time frame: PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3.
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 Healthy Volunteers | Summary of Pharmacokinetic Parameters (AUC(0-tau) ) | 40.1 nmol*h/L | Geometric Coefficient of Variation 11.4 |
| Placebo Healthy Volunteers | Summary of Pharmacokinetic Parameters (AUC(0-tau) ) | 27.4 nmol*h/L | Geometric Coefficient of Variation 17.3 |
| AZD7624 COPD | Summary of Pharmacokinetic Parameters (AUC(0-tau) ) | 13.3 nmol*h/L | Geometric Coefficient of Variation 50.4 |
| Placebo COPD | Summary of Pharmacokinetic Parameters (AUC(0-tau) ) | 3.88 nmol*h/L | Geometric Coefficient of Variation 28.5 |
| AZD7624 Healthy Volunteers Cohort 2 | Summary of Pharmacokinetic Parameters (AUC(0-tau) ) | 9.31 nmol*h/L | Geometric Coefficient of Variation 12.7 |
| AZD7624 Healthy Volunteers Cohort 3 | Summary of Pharmacokinetic Parameters (AUC(0-tau) ) | 15.2 nmol*h/L | Geometric Coefficient of Variation 33.3 |
Secondary
Summary of Pharmacokinetic Parameters (Cmax)
Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken.
Time frame: PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3.
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 Healthy Volunteers | Summary of Pharmacokinetic Parameters (Cmax) | 11.9 nmol/L | Geometric Coefficient of Variation 13.4 |
| Placebo Healthy Volunteers | Summary of Pharmacokinetic Parameters (Cmax) | 15.6 nmol/L | Geometric Coefficient of Variation 38.3 |
| AZD7624 COPD | Summary of Pharmacokinetic Parameters (Cmax) | 3.08 nmol/L | Geometric Coefficient of Variation 54.6 |
| Placebo COPD | Summary of Pharmacokinetic Parameters (Cmax) | 2.14 nmol/L | Geometric Coefficient of Variation 49.5 |
| AZD7624 Healthy Volunteers Cohort 2 | Summary of Pharmacokinetic Parameters (Cmax) | 6.23 nmol/L | Geometric Coefficient of Variation 22.8 |
| AZD7624 Healthy Volunteers Cohort 3 | Summary of Pharmacokinetic Parameters (Cmax) | 8.07 nmol/L | Geometric Coefficient of Variation 39.5 |
Secondary
Summary of Pharmacokinetic Parameters (Cmin)
Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken.
Time frame: PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3.
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 Healthy Volunteers | Summary of Pharmacokinetic Parameters (Cmin) | 0.797 nmol/L | Geometric Coefficient of Variation 22.2 |
| Placebo Healthy Volunteers | Summary of Pharmacokinetic Parameters (Cmin) | 0.602 nmol/L | Geometric Coefficient of Variation 15.7 |
| AZD7624 COPD | Summary of Pharmacokinetic Parameters (Cmin) | 0.355 nmol/L | Geometric Coefficient of Variation 47.3 |
| Placebo COPD | Summary of Pharmacokinetic Parameters (Cmin) | 0.183 nmol/L | Geometric Coefficient of Variation 44 |
| AZD7624 Healthy Volunteers Cohort 2 | Summary of Pharmacokinetic Parameters (Cmin) | 0.453 nmol/L | Geometric Coefficient of Variation 18.6 |
| AZD7624 Healthy Volunteers Cohort 3 | Summary of Pharmacokinetic Parameters (Cmin) | 0.719 nmol/L | Geometric Coefficient of Variation 36.9 |