AZD8848 Single Ascending Dose Study

Phase 1

Completed

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

Detailed Description: 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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
AZD8848	AZD8848	-
Placebo	Placebo	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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
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
Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma	Baseline, 48 Hours	Smmarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix
Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum	Baseline, 24 Hours.	Summarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix