Study in Healthy Volunteers to Assess the Pharmacokinetics of Midazolam Administered Alone and in Combination With Vandetanib

A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Midazolam, a
CYP3A4 Substrate, in Healthy Subjects When Administered Alone and in Combination with a
Single Dose of 800-mg Vandetanib (CAPRELSA)

Inclusion Criteria:

- Provision of signed and dated, written informed consent prior to any study

- specific procedures:

- Volunteers must be males or females aged 18 to 50 years and with a weight of at
least 50 kg and body mass index (BMI) between 18 and 30 kg/m2, inclusive

- Females must have a negative pregnancy test at screening and on admission to the
study center.

- Females must not be lactating and must be of non-childbearing potential defined
as postmenopausal or documentation of irreversible surgical sterilization.

Exclusion Criteria:

- History of any clinically significant disease or disorder such as gastrointestinal,
hepatic, renal or skin disease.

- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity,

- Volunteers who smoke more than 5 cigarettes per day or are unable to refrain from
smoking while resident in the study center

- Screening blood pressure of greater than 140/90 mmHg and/or a resting heart rate of
less than 45 beats per minute (repeat test allowed at the Investigator's discretion)

- Clinically significant abnormal12-lead ECG as assessed by the Investigator,

- QTcF interval greater than 450 ms

- Any positive result on screening for:

- serum hepatitis B surface antigen,

- hepatitis C antibody, and

- human immunodeficiency virus (HIV), or

- Positive screen for drugs of abuse.