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)

Sanofi1 site in 1 country16 target enrollmentApril 2012

ConditionsHealthy Volunteers

InterventionsMidazolam vandetanib

DrugsMidazolam vandetanib

Overview

Phase: Phase 1
Intervention: Midazolam
Conditions: Healthy Volunteers
Sponsor: Sanofi
Enrollment: 16
Locations: 1
Primary Endpoint: AUC for midazolam administered alone and in combination with vandetanib 800 mg
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

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)

Registry

clinicaltrials.gov

Start Date

April 2012

End Date

July 2012

Last Updated

9 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Sanofi

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

midazolam then midazolam + vandetanib

Midazolam alone followed by midazolam in combination with vandetanib

Intervention: Midazolam

midazolam then midazolam + vandetanib

Midazolam alone followed by midazolam in combination with vandetanib

Intervention: vandetanib

Outcomes

Primary Outcomes

AUC for midazolam administered alone and in combination with vandetanib 800 mg

Time Frame: 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

Time Frame: Predose,0.5,1,1.5,2,3,4,6,8,12,16,24,30,36,48 hrs post dose

Secondary Outcomes

Vital signs data(Treatment period from 7 to 14 days)
Laboratory data(Treatment period from 7 to 14 days)
Frequency and severity of adverse events(Treatment period from 7 to 14 days)
ECG 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)