Clinical trial NCT01560234: AZD8848 Single Ascending Dose Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Safety
tolerability
healthy
pharmacokinetic
pharmacodynamic
inhaled
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-03-22
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events
timeFrame: Screening up to Day 13
measure: Summary for Lymphocytes Laboratory Results
timeFrame: Baseline, Day 1, Day 2, Day 3, and Follow up (up to Day 13)
Secondary outcomes:
measure: Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L)
timeFrame: On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
measure: Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L)
timeFrame: On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
measure: Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L)
timeFrame: On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
measure: Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma
timeFrame: Baseline, 24 Hours.
measure: Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma
timeFrame: Baseline, 48 Hours
measure: Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum
timeFrame: Baseline, 24 Hours.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D, 35 Gatehouse Drive, MA 02451 USA
name: Ajay Aggarwal
role: STUDY_DIRECTOR
affiliation: Quintile Drug Research Unit at Guy's Hospital Quintiles Ltd 6 Newcomen Street London SE1 1YR United Kingdom
name: James Ritter, BA,MA D Phil,BM BCh,MRCP,FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.