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

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT01544140

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Midazolam Drug: vandetanib	Phase 1

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)

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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)

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: midazolam then midazolam + vandetanib Midazolam alone followed by midazolam in combination with vandetanib	Drug: Midazolam Oral syrup 7.5 mg, single dose Drug: vandetanib Oral tablets, 800 mg, single dose

Arm

Intervention/Treatment

Experimental: midazolam then midazolam + vandetanib

Midazolam alone followed by midazolam in combination with vandetanib

Drug: Midazolam

Oral syrup 7.5 mg, single dose

Drug: vandetanib

Oral tablets, 800 mg, single dose

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.