A Phase I Study in Healthy Volunteers to Assess the Effect of Cytochrome3A4 (CYP3A4) Inhibitors (Diltiazem and Itraconazole) on the Pharmacokinetics (PK) of AZD3293 and the Effects of AZD3293 on the Pharmacokinetics of Midazolam, a Cytochrome 3A4 and Cytochrome 3A5 (CYP3A4/CYP3A5) Substrate
Information source: AstraZeneca
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy Volunteers; Pharmacologic Action
Intervention: Group 1 AZD3293 (Drug); Group 2 AZD3293 (Drug); Group 3 AZD3293 (Drug); Group 1 Itraconazole (Drug); Group 2 Diltiazem (Drug); Group 3 Midazolam (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: AstraZeneca Official(s) and/or principal investigator(s): Apinya Vutikullird, DO, Principal Investigator, Affiliation: WCCT Global
Summary
This study is a single-center, open-label, 3-group, fixed-sequence drug-drug interaction
study to assess the effect of coadministration of multiple-dose itraconazole or diltiazem on
the single-dose PK of AZD3293 and the effects of coadministration of single- and
multiple-dose AZD3293 on the single-dose PK of midazolam. The study will also evaluate the
safety and tolerability of single and multiple oral doses of AZD3293, alone and in
combination with itraconazole, diltiazem, and midazolam in healthy young subjects. AZD3293 is
being developed for the treatment of Alzheimer's disease
Clinical Details
Official title: A Phase I, Single-center, Open-label, 3-group, Fixed-sequence Study to Assess the Effect of Itraconazole, a Potent CYP3A4 Inhibitor, or Diltiazem, a Moderate CYP3A4 Inhibitor, on the Pharmacokinetics of AZD3293 and the Effects of AZD3293 on the Pharmacokinetics of Midazolam, a CYP3A4/CYP3A5 Substrate, in Healthy Young Male and Female Volunteers
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: The effect of multiple-dose co-administration of CYP3A4 inhibitors on the single-dose PK of AZD3293 measured by assessment of area under the curve over the time (AUC) and maximum concentrationThe effect of multiple-dose AZD3293 administration (including the reversibilityof any of its effects) on the single-dose PK of a CYP3A4/CYP3A5 substrate (midazolam) by assessment of area under the curve over the time (AUC) and maximum concentration
Secondary outcome: Safety profile in terms of Adverse events assessmentSafety and tolerability in terms of lab tests assessment (hematology, chemistry, urinalysis) Safety and tolerability in terms of vital signs assessment (blood pressure, pulse and body temperature) and physical exams Safety and tolerability by assessing changes in electrocardiogram (ECG) parameters Safety and tolerability by assessing telemetry records Suicidality mesured by Columbia-Suicide Severity Rating Scale (C-SSRS)
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Provision of signed, written, and dated informed consent prior to any study-specific
procedures Male and nonfertile female healthy subjects, aged 18 to 55 years at the
time of consent
- Body weight ≥50 to ≤100 kg and body mass index (BMI) ≥19 to ≤30 kg/m2
- Clinically normal findings on physical examination in relation to age, as judged by
the Investigator
- Male healthy subjects must be willing to use barrier contraception, ie, condoms, even
if their partners are post-menopausal, surgically sterile, or using accepted
contraceptive methods, from the first day of dosing until 3 months after the last
dose of investigational product (IP)
Exclusion Criteria:
- Participation in any prior study of AZD3293
- History of any clinically significant disease or disorder which, in the opinion of
the Investigator, may put the subject at risk because of participation in the study,
may influence the results, or may limit the subject's ability to participate in the
study
- History or presence of gastrointestinal, hepatic or renal disease or any other
condition known to interfere with absorption, distribution, metabolism or excretion
of drugs
- History of previous or ongoing psychiatric disease/condition including psychosis,
affective disorder, anxiety disorder, borderline state and personality disorder
according to the criteria in the Diagnostic and Statistical Manual of Mental
Disorders, 4th edition (DSM IV), as assessed by the Mini-International
Neuropsychiatric Interview (MINI)
Locations and Contacts
Research Site, Cypress, California, United States
Additional Information
Starting date: December 2013
Last updated: April 25, 2014
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