Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4451

• Provide a signed and dated, written informed consent prior to any study specific procedures being performed. including the genetic sampling and analyses. If a volunteer declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the volunteer. The volunteer will not be excluded from other aspects of the study described in this protocol.
• Healthy male and female (of non-childbearing potential) volunteers 18 to 55 years old inclusive with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test at screening and on admission to the unit, must not be nursing and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
• Post-menopausal defined as amenorrhoea for at least 12 months following cessation of all exogenous hormonal treatments and with FSH levels in the laboratory defined post-menopausal range
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation Male volunteers should be willing to use barrier contraception for example, condoms and spermicide, from the day of dosing until at least 3 months after dosing with the investigational product.
• Have a body mass index (BMI) between 19 and 30 kg/m2 (BMI \<30.5 =30) and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria:

• History of gastrointestinal surgery (other than cholecystectomy or appendectomy) or unintentional rapid weight loss.
• A positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV).
• History of any of the following as judged by the Investigator: History of psychiatric disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders text revision; Medically diagnosed depression in the 6 months prior to dosing; Bipolar disorder; Use of psychoactive medication (including mood stabilizers) in the 6 months prior to dosing; Electroconvulsive therapy in the 6 months prior to dosing; History of seizures 1 year prior to dosing; History of severe dystonic reaction to other drugs.
• History of syncope, fainting or of vasovagal reactions; history of arrhythmias, and/or postural hypotension. The inclusion of volunteers meeting the above criteria may be decided on a case-by-case basis after consultation between the Investigator and AZ CPA physician.
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.