Clinical trial NCT01544140: Study in Healthy Volunteers to Assess the Pharmacokinetics of Midazolam Administered Alone and in Combination With Vandetanib
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Phase 1
healthy volunteers
pharmacokinetics
vandetanib
midazolam
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-03-05
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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)

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
* Positive screen for drugs of abuse.

Primary outcomes:
measure: AUC for midazolam administered alone and in combination with vandetanib 800 mg
timeFrame: Predose,0.5,1,1.5,2,3,4,6,8,12,16,24,30,36,48 hrs post dose
measure: Cmax for midazolam administered alone and in combination with vandetanib 800 mg
timeFrame: Predose,0.5,1,1.5,2,3,4,6,8,12,16,24,30,36,48 hrs post dose
Secondary outcomes:
measure: Frequency and severity of adverse events
timeFrame: Treatment period from 7 to 14 days
measure: ECG data
timeFrame: Treatment period from 7 to 14 days
measure: Laboratory data
timeFrame: Treatment period from 7 to 14 days
measure: Vital signs data
timeFrame: Treatment period from 7 to 14 days
measure: Other PK parameters for midazolam administered alone and in combination with vandetanib 800 mg
timeFrame: Predose,0.5,1,1.5,2,3,4,6,8,12,16,24,30,36,48 hrs post dose
measure: Vandetanib PK parameters for vandetanib in combination with midazolam
timeFrame: 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
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Johansson S, Read J, Oliver S, Steinberg M, Li Y, Lisbon E, Mathews D, Leese PT, Martin P. Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine. Clin Pharmacokinet. 2014 Sep;53(9):837-47. doi: 10.1007/s40262-014-0161-2.