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

Study Overview
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Brief Summary
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The purpose of this study in healthy volunteers is to assess the Pharmacokinetics (PK) of Midazolam administered alone and in combination with Vandetanib.

Detailed Description
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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)

Official Title
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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)

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Midazolam
* Drug: vandetanib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: midazolam then midazolam + vandetanib<br>Midazolam alone followed by midazolam in combination with vandetanib | Drug: Midazolam<br>* Oral syrup 7.5 mg, single dose<br>Drug: vandetanib<br>* Oral tablets, 800 mg, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC for midazolam administered alone and in combination with vandetanib 800 mg |  | Predose,0.5,1,1.5,2,3,4,6,8,12,16,24,30,36,48 hrs post dose | 
| Cmax for midazolam administered alone and in combination with vandetanib 800 mg |  | Predose,0.5,1,1.5,2,3,4,6,8,12,16,24,30,36,48 hrs post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of adverse events |  | Treatment period from 7 to 14 days | 
| ECG data |  | Treatment period from 7 to 14 days | 
| Laboratory data |  | Treatment period from 7 to 14 days | 
| Vital signs data |  | Treatment period from 7 to 14 days | 
| Other PK parameters for midazolam administered alone and in combination with vandetanib 800 mg |  | Predose,0.5,1,1.5,2,3,4,6,8,12,16,24,30,36,48 hrs post dose | 
| Vandetanib PK parameters for vandetanib in combination with midazolam |  | Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216 hrs post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, healthy volunteers, pharmacokinetics, vandetanib, midazolam