A phase 1, single centre, single dose, double-blind, double-dummy, four-way crossover, placebo-controlled, randomized study to investigate the effects of AZD7325 on sedation, cognition and EEG in comparison with lorazepam in healthy male volunteers.

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

1. Provision of written informed consent
2. Healthy male subjects aged 18 to 55 years (extremes inclusive) on sceening
3. Body Mass Index (BMI) >= 18 and <= 30 kg/m2

Exclusion Criteria

1. Clinically relevant disease and/or abnormalities (past or present) which in the opinion of the investigator, may either put the subject at risk to participate in the study or may influence the results of the study or the subject*s ability to participate in the study
2. Psychiatric, medical, and surgical history that may interfere with the objectives of the study
3. Subject*s partner is planning pregnancy within 3 months of last dosing
4. Significant illness, as judged by the investigator, within 2 weeks of the first study day
5. Clinically relevant abnormalities in physical examinations, vital signs, clinical
chemistry, thyroid function test, hematology or urinalysis at screening as judged by the investigator and/or sponsor
6. ECG with a QTcF interval of >450 or <360msec at screening
7. History of clinically significant arrhythmias (including II degree atrioventricular block and Wolff-Parkinson-White Syndrome)
8. Any other clinically significant abnormal baseline ECG and/or abnormalities in ECG
as judged by the investigator and/or sponsor at the screening visit
9. Positive human immune deficiency virus (HIV), Hepatitis B or Hepatitis C test
10. Current manifestation of any clinically significant allergic disorder with the exception of seasonal allergies
11. Use of any medication or herbal preparation within 14 days of the first study day through the Follow-up Visit other than paracetamol (up to 3g/day) and incidental use of prescription or non-prescription medication approved by the investigator.
12. Enrollment in another concurrent investigational study or intake of an investigational drug within 3 months prior to the start of the study or more than 4 times a year.
13. Donation of blood in the past 3 months.
14. Smoking in excess of 5 cigarettes per day or the equivalent within 28 days prior to the first study day or inability to refrain from smoking from 22:00 prior to each study day
15. Current regular user (including *recreational uses*) of any illicit drugs or history of drug or alcohol abuse. Subjects who have a positive drug screen at screening are excluded.
16. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at the CPU)
17. Prior randomization in a trial with AZD7325
18. Inability to understand or cooperate with the requirements of this study

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To investigate the pharmacodynamic (PD) effects of single oral doses of AZD7325<br /><br>on sedation and cognition in comparison with lorazepam, a widely used<br /><br>non-selective GABA-A modulator for anxiolysis.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. To evaluate the safety and tolerability of AZD7325 by assessing adverse<br /><br>events, vital<br /><br>signs, laboratory parameters, and ECGs.<br /><br>2. To measure the effects of single oral doses of AZD7325 with<br /><br>electroencephalogram (EEG)<br /><br>and to assess whether the EEG power spectral changes of AZD7325 seen in animal<br /><br>studies<br /><br>are observed in humans.<br /><br>3. To determine the effects of single oral doses of AZD7325 on body sway and to<br /><br>compare<br /><br>its effects to those of lorazepam.<br /><br>4. To investigate the pharmacokinetic (PK) profile of AZD7325 after single oral<br /><br>doses<br /><br>administration. Mathematical PK/PD modelling to correlate the relationships<br /><br>between<br /><br>plasma concentration and effects for changes in CNS measurements will be<br /><br>attempted.</p><br>