To Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses AZD8848 in Healthy Subjects

Study Overview
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Brief Summary
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This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD8848 in healthy subjects.

Detailed Description
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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

Official Title
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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

Conditions
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Safety,, Tolerability,, Healthy Subjects

Intervention / Treatment
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* Drug: AZD8848
* Drug: Placebo to match AZD8848


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture Women must be of non-childbearing potential or must have been stable on a highly effective contraceptive for at least 3 months prior to Screening and be willing to continue on the chosen contraceptive with additonal use of condom until 3 months postdose Male subjects should be willing to use barrier contraception ie, condoms, from the first day of investigational product administration until 3 months after the last administration of investigational product Have a body mass index (BMI) between 18 and 32 kg/m2 and weigh at least 50 kg and no more than 110 kg Women must have a negative pregnancy test at screening and on admission to the study centre, must have a date of last menstruation, must not be lactating or must be of non-childbearing potential Exclusion Criteria: Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: SBP >140 mmHg, Diastolic blood pressure (DBP) >90 mmHg, Heart rate <40 or >85 beats per minute History of asthma or allergic rhinitis Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class as AZD8848 - Any clinically significant abnormalities in clinical chemistry.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD8848<br>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. | Drug: AZD8848<br>* Multiple doses inhaled IMP via a nebulizer<br>|
| Placebo Comparator: Placebo to match AZD8848<br>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. | Drug: Placebo to match AZD8848<br>* Multiple doses inhaled matching placebo via a nebulizer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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. | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety,, tolerability,, Phase I,, pharmacokinetic,, pharmacodynamic,, inhaled