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This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD8848 in healthy subjects.
A Phase 1, Single Centre, Double-blind, Randomised, Placebo-controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics after Administration of Multiple Ascending (MAD) Once Weekly Inhaled Doses of AZD8848 in Healthy Subjects
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD8848 | Experimental | Subjects will participate in 1 of 3 groups and receive multiple doses of AZD8848 or matching placebo In each group 6 subjects will receive AZD8848 and 2 subjects will receive matching placebo. |
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| Placebo to match AZD8848 | Placebo Comparator | Subjects will participate in 1 of 3 groups and receive multiple doses of AZD8848 or matching placebo. In each group 6 subjects will receive AZD8848 and 2 subjects will receive matching placebo. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD8848 | Drug | Multiple doses inhaled IMP via a nebulizer |
| |
| Placebo to match AZD8848 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline up to 77 days in safety variables (adverse events, vital signs, body temperature, physical exams, ECGs, clinical laboratory tests, pulse oximetry, spirometry). | From screening visit (Day -42) through the Treatment Follow Up visit (Day 35) at multiple timepoints up to 77 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Single dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma and urine from healthy subjects | PK parameters: Cmax, tmax, area under the plasma concentration-time curve from zero to 24 hours postdose (AUC(0-24)), from zero to the time of the last quantifiable concentration (AUC(0-t)) and from zero to infinity (AUC), CL/F, Vz/F, CLR and Ae |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tim Mant, BSc, MB BS, MRCP, FRCP, FFPM | Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen Street London SE1 1YR UK | Principal Investigator |
| Aray Aggarwal | AstraZeneca Pharmaceuticals 35 Gathouse Drive, Waltham, Ma 02451 United States | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26933507 | Derived | Delaney S, Biffen M, Maltby J, Bell J, Asimus S, Aggarwal A, Kraan M, Keeling D. Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848. BMJ Open Respir Res. 2016 Feb 23;3(1):e000113. doi: 10.1136/bmjresp-2015-000113. eCollection 2016. |
| Label | URL |
|---|---|
| Study Synopsis | View source |
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| ID | Term |
|---|---|
| D053120 | Respiratory Aspiration |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000609563 | AZD8848 |
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| Drug |
Multiple doses inhaled matching placebo via a nebulizer |
|
| Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose. Urine: From days 1 and 22, pre-dose, 0 to 6, 6 to 12 and 12 to 24 hrs post dose |
| Multiple dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma | PK parameters: AUC accumulation ratio and Cmax accumulation ratio | Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose |
| Pharmacodynamic effect after multiple doses of inhaled AZD8848 by assessment of the CXCL10 biomarker concentration in plasma | Pharmacodynamic effect: CXCL10 concentration and change-from-baseline ratios in plasma | From Days 1 and 22, pre-dose, 24 and 48 hrs post dose. One sample 7 to 13 days post last dose. |