To Assess the Safety, Tolerability, and Pharmacokinetics of AZD7624 in Healthy Volunteers and COPD Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Groups 1-4 multiple ascending doses of AZD7624 Healthy subjects will participate in groups 1-3. In each group 6 subjects will receive AZD7624 and 2 will receive matching placebo. COPD patients will participate in group 4. In this group, 8 patients will receive AZD7624 and 2 patients will receive matching placebo. |
Drug: AZD7624
Multiple ascending doses (starting from 300 µg lung deposited dose up to 1200 µg) inhaled IMP via a nebulizer
|
| Placebo Comparator: 2 Groups 1-4 multiple ascending doses of placebo Healthy subjects will participate in groups 1-3. In each group 6 subjects will receive AZD7624 and 2 will receive matching placebo. COPD patients will participate in group 4. In this group, 8 patients will receive AZD7624 and 2 will receive matching placebo. |
Drug: Placebo to match
Multiple doses inhaled placebo via a nebulizer
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | London | United Kingdom |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Principal Investigator: Saeed Khan, MBBS, MRCP, Quintiles Drg Research Centre At Guys Hosipital, 6 Newcomen Street London SE1 1YR
- Study Chair: Naimish Patel, MD, AstraZeneca, Wilmington, US
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- D2550C00002
Study Results
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 Detail | 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. |
| Arm/Group Title | AZD7624 Healthy Volunteers | Placebo Healthy Volunteers | AZD7624 COPD | Placebo COPD |
|---|---|---|---|---|
| Arm/Group Description | Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily | Healthy Volunteers with Placebo, once daily or twice daily | COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily | COPD Patients with Placebo, once daily |
| Period Title: Overall Study | ||||
| STARTED | 23 | 8 | 11 | 5 |
| COMPLETED | 23 | 6 | 9 | 5 |
| NOT COMPLETED | 0 | 2 | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | AZD7624 Healthy Volunteers | Placebo Healthy Volunteers | AZD7624 COPD | Placebo COPD | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily | Healthy Volunteers with Placebo, once daily or twice daily | COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily | COPD Patients with Placebo, once daily | Total of all reporting groups |
| Overall Participants | 23 | 8 | 11 | 5 | 47 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
36
(9.7)
|
32
(9.1)
|
65
(9.7)
|
65
(8.7)
|
45.3
(17.1)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
0
0%
|
0
0%
|
1
9.1%
|
2
40%
|
3
6.4%
|
| Male |
23
100%
|
8
100%
|
10
90.9%
|
3
60%
|
44
93.6%
|
Outcome Measures
| Title | Adverse Events |
|---|---|
| Description | Summary of number of subjects who had at least one adverse event in any category (Safety analysis set) |
| Time Frame | Up to 24 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | AZD7624 Healthy Volunteers | Placebo Healthy Volunteers | AZD7624 COPD | Placebo COPD |
|---|---|---|---|---|
| Arm/Group Description | Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily | Healthy Volunteers with Placebo, once daily or twice daily | COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily | COPD Patients with Placebo, once daily |
| Measure Participants | 23 | 8 | 11 | 5 |
| Any Adverse Event (AE) |
6
26.1%
|
3
37.5%
|
7
63.6%
|
2
40%
|
| Any AE with outcome = death |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Any SAE (including events with outcome = death) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Any AE leading to discontinuation |
0
0%
|
1
12.5%
|
2
18.2%
|
0
0%
|
| Title | Summary of Pharmacokinetic Parameters (AUC(0-tau) ) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set |
| Arm/Group Title | AZD7624 COPD Cohort 4 | AZD7624 Healthy Volunteers Cohort 5 | AZD7624 COPD Cohort 6 | AZD7624 Healthy Volunteers Cohort 1 | AZD7624 Healthy Volunteers Cohort 2 | AZD7624 Healthy Volunteers Cohort 3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | COPD patients on Cohort 4 with 1932 µg delivered dose of AZD7624 , once daily | Healthy volunteers on Cohort 5 with 2053 µg delivered dose of AZD7624 , once daily | COPD patients on Cohort 6 with 966 µg delivered dose of AZD7624, once daily | Healthy volunteers on Cohort 1 with 261 µg delivered dose of AZD7624, twice daily | Healthy volunteers on Cohort 2 with 522 µg delivered dose of AZD7624, twice daily | Healthy volunteers on Cohort 3 with 1027 µg delivered dose of AZD7624, twice daily |
| Measure Participants | 3 | 6 | 6 | 6 | 6 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
40.1
(11.4)
|
27.4
(17.3)
|
13.3
(50.4)
|
3.88
(28.5)
|
9.31
(12.7)
|
15.2
(33.3)
|
| Title | Summary of Pharmacokinetic Parameters (Cmax) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set |
| Arm/Group Title | AZD7624 COPD Cohort 4 | AZD7624 Healthy Volunteers Cohort 5 | AZD7624 COPD Cohort 6 | AZD7624 Healthy Volunteers Cohort 1 | AZD7624 Healthy Volunteers Cohort 2 | AZD7624 Healthy Volunteers Cohort 3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | COPD patients on Cohort 4 with 1932 µg delivered dose of AZD7624 , once daily | Healthy volunteers on Cohort 5 with 2053 µg delivered dose of AZD7624 , once daily | COPD patients on Cohort 6 with 966 µg delivered dose of AZD7624, once daily | Healthy volunteers on Cohort 1 with 261 µg delivered dose of AZD7624, twice daily | Healthy volunteers on Cohort 2 with 522 µg delivered dose of AZD7624, twice daily | Healthy volunteers on Cohort 3 with 1027 µg delivered dose of AZD7624, twice daily |
| Measure Participants | 3 | 6 | 6 | 6 | 6 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
11.9
(13.4)
|
15.6
(38.3)
|
3.08
(54.6)
|
2.14
(49.5)
|
6.23
(22.8)
|
8.07
(39.5)
|
| Title | Summary of Pharmacokinetic Parameters (Cmin) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set |
| Arm/Group Title | AZD7624 COPD Cohort 4 | AZD7624 Healthy Volunteers Cohort 5 | AZD7624 COPD Cohort 6 | AZD7624 Healthy Volunteers Cohort 1 | AZD7624 Healthy Volunteers Cohort 2 | AZD7624 Healthy Volunteers Cohort 3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | COPD patients on Cohort 4 with 1932 µg delivered dose of AZD7624 , once daily | Healthy volunteers on Cohort 5 with 2053 µg delivered dose of AZD7624 , once daily | COPD patients on Cohort 6 with 966 µg delivered dose of AZD7624, once daily | Healthy volunteers on Cohort 1 with 261 µg delivered dose of AZD7624, twice daily | Healthy volunteers on Cohort 2 with 522 µg delivered dose of AZD7624, twice daily | Healthy volunteers on Cohort 3 with 1027 µg delivered dose of AZD7624, twice daily |
| Measure Participants | 3 | 6 | 6 | 6 | 6 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
0.797
(22.2)
|
0.602
(15.7)
|
0.355
(47.3)
|
0.183
(44.0)
|
0.453
(18.6)
|
0.719
(36.9)
|
Adverse Events
| Time Frame | Up to 24 days | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | AZD7624 Healthy Volunteers | Placebo Healthy Volunteers | AZD7624 COPD | Placebo COPD | ||||
| Arm/Group Description | Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily | Healthy Volunteers with Placebo, once daily or twice daily | COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily | COPD Patients with Placebo, once daily | ||||
All Cause Mortality |
||||||||
| AZD7624 Healthy Volunteers | Placebo Healthy Volunteers | AZD7624 COPD | Placebo COPD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| AZD7624 Healthy Volunteers | Placebo Healthy Volunteers | AZD7624 COPD | Placebo COPD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/23 (0%) | 0/8 (0%) | 0/11 (0%) | 0/5 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| AZD7624 Healthy Volunteers | Placebo Healthy Volunteers | AZD7624 COPD | Placebo COPD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/23 (26.1%) | 3/8 (37.5%) | 7/11 (63.6%) | 2/5 (40%) | ||||
| Gastrointestinal disorders | ||||||||
| Mouth ulceration, Dry mouth, Nausea | 1/23 (4.3%) | 2/8 (25%) | 1/11 (9.1%) | 0/5 (0%) | ||||
| General disorders | ||||||||
| Chest discomfort, Vessel puncture site bruise | 1/23 (4.3%) | 2/8 (25%) | 2/11 (18.2%) | 0/5 (0%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis, Upper respiratory tract infection, Rhinitis, Tooth abscess | 2/23 (8.7%) | 1/8 (12.5%) | 3/11 (27.3%) | 0/5 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back Pain, Musculoskeletal chest pain | 0/23 (0%) | 1/8 (12.5%) | 1/11 (9.1%) | 1/5 (20%) | ||||
| Nervous system disorders | ||||||||
| Dizziness, Headache, Presyncope | 0/23 (0%) | 2/8 (25%) | 1/11 (9.1%) | 1/5 (20%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough, Bronchospasm, Wheezing | 4/23 (17.4%) | 1/8 (12.5%) | 1/11 (9.1%) | 0/5 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Papule, Rash | 2/23 (8.7%) | 0/8 (0%) | 1/11 (9.1%) | 0/5 (0%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Naimish Patel |
|---|---|
| Organization | AstraZeneca |
| Phone | +1 781 839 4061 |
| Naimish.Patel@astrazeneca.com |
- D2550C00002