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.