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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01544140
First received: February 23, 2012
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Healthy Volunteers
Drug: Midazolam
Drug: vandetanib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency and severity of adverse events [ Time Frame: Treatment period from 7 to 14 days ] [ Designated as safety issue: Yes ]
  • ECG data [ Time Frame: Treatment period from 7 to 14 days ] [ Designated as safety issue: Yes ]
  • Laboratory data [ Time Frame: Treatment period from 7 to 14 days ] [ Designated as safety issue: Yes ]
  • Vital signs data [ Time Frame: Treatment period from 7 to 14 days ] [ Designated as safety issue: Yes ]
  • Other PK parameters 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 ] [ Designated as safety issue: No ]
  • Vandetanib PK parameters for vandetanib in combination with midazolam [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: April 2012
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01544140

Locations
United States, Kansas
Research Site
Overland Park, Kansas, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: James Vasselli, SCIENCE DIR AstraZeneca
Principal Investigator: Philip Leese, MD Quintiles
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01544140     History of Changes
Other Study ID Numbers: D4200C00103
Study First Received: February 23, 2012
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Phase 1
healthy volunteers
pharmacokinetics
vandetanib
midazolam

Additional relevant MeSH terms:
Midazolam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014