AZD8848 Single Ascending Dose Study

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

Detailed Description
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A Double-blind, Placebo-controlled, Randomised Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Inhaled Doses of AZD8848 in Healthy Subjects

Official Title
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A Double-blind, Placebo-controlled, Randomised Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Inhaled Doses of AZD8848 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: AZD8848
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men or women aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venipuncture. Women can be of childbearing potential and must have been stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 (screening) and be willing to continue on the chosen contraceptive method Male subjects should be willing to use a condom (with spermicide) to prevent pregnancy and drug exposure of a female partner and refrain from donating sperm or fathering a child from the day of the investigational product administration until 3 months Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg Ability to produce sputum of good enough quality for assessment of biomarkers 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) 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 History of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT syndrome, or sudden death) History of asthma or allergic rhinitis

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> | Drug: AZD8848<br>* Single dose, oral inhalation (nebuliser solution)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Single dose, oral inhalation (nebuliser solution)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Summary of number of subjects who had at least one adverse event | Screening up to Day 13 | 
| Summary for Lymphocytes Laboratory Results |  | Baseline, Day 1, Day 2, Day 3, and Follow up (up to Day 13) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L) |  | On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h | 
| Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L) |  | On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h | 
| Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L) |  | On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h | 
| Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | Smmarizes the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix | Baseline, 24 Hours. | 
| Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | Smmarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix | Baseline, 48 Hours | 
| Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | Summarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix | Baseline, 24 Hours. | 

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