Clinical trial NCT02010970: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Pharmacologic Action
Keywords: phase I
healthy volunteers
AZD3293
itraconazole
diltiazem
medazolam
drug interactions
Pharmacokinetics
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-12-13
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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


Eligibility 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)

Primary outcomes:
measure: 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 concentration
timeFrame: up to day 13
measure: The 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
timeFrame: up to day 17
Secondary outcomes:
measure: Safety profile in terms of Adverse events assessment
timeFrame: from Baseline and up to day 18
measure: Safety and tolerability in terms of lab tests assessment (hematology, chemistry, urinalysis)
timeFrame: from Baseline and up to day 18
measure: Safety and tolerability in terms of vital signs assessment (blood pressure, pulse and body temperature) and physical exams
timeFrame: from baseline and up till day 18
measure: Safety and tolerability by assessing changes in electrocardiogram (ECG) parameters
timeFrame: from Baseline and up to day 18
measure: Safety and tolerability by assessing telemetry records
timeFrame: from baseline and up to day 13
measure: Suicidality mesured by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: from Baseline and up till day 18
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Research Site
state: California
Study officials:
affiliation: WCCT Global
name: Apinya Vutikullird, DO
role: PRINCIPAL_INVESTIGATOR
References: