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

NCT ID: NCT02010970

Last Updated: 2014-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2014-02-28

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

Conditions

Healthy Volunteers; Pharmacologic Action

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Group 1 AZD3293-itraconazole

Subjects from Group 1 will receive a single dose of AZD3293 as an oral solution on Day 1 . In Group 1, itraconazole will be administered orally twice daily starting on Day 5 for 9 consecutive days (Days 5 to 13). On Day 8, a single dose of AZD3293 will be coadministered as an oral solution after the morning dose of itraconazole. Group 1 subjects will be discharged on Day 14.

Group Type: EXPERIMENTAL

Group 1 AZD3293

Intervention Type: DRUG

AZD3293 oral solution

Group 1 Itraconazole

Intervention Type: DRUG

itraconazole capsule

Group 2 AZD3293-diltiazem

Subjects from Group 2 will receive a single dose of AZD3293 as an oral solution on Day 1 . In Group 2, diltiazem will be administered orally once daily starting on Day 5, for 9 consecutive days (Days 5 to 13). On Day 8, a single dose of AZD3293 will be coadministered as an oral solution after the diltiazem dose. Group 2 subjects will be discharged on Day 14.

Group Type: EXPERIMENTAL

Group 2 AZD3293

Intervention Type: DRUG

AZD3293 oral solution

Group 2 Diltiazem

Intervention Type: DRUG

Diltiazem ER tablet

Group 3 AZD3293-midazolam

Subjects from Group 3 will receive a single dose of midazolam on Day 1 . AZD3293 will be administered as an oral solution once daily starting on Day 2 for 9 consecutive days (Days 2 to 10) followed by a 7 day wash-out period. On Day 8 and Day 17 a single dose of midazolam will be administered. Group 3 subjects will be discharged on Day 18

Group Type: EXPERIMENTAL

Group 3 AZD3293

Intervention Type: DRUG

AZD3293 oral solution

Group 3 Midazolam

Intervention Type: DRUG

midazolam syrup

Interventions

Group 1 AZD3293

AZD3293 oral solution

Intervention Type: DRUG

Group 2 AZD3293

AZD3293 oral solution

Intervention Type: DRUG

Group 3 AZD3293

AZD3293 oral solution

Intervention Type: DRUG

Group 1 Itraconazole

itraconazole capsule

Intervention Type: DRUG

Group 2 Diltiazem

Diltiazem ER tablet

Intervention Type: DRUG

Group 3 Midazolam

midazolam syrup

Intervention Type: DRUG

Other Intervention Names

beta secretase inhibitor; beta secretase inhibitor; beta secretase inhibitor; azole antifungal; calcium channel blocker; benzodiazepine

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Apinya Vutikullird, DO

Role: PRINCIPAL_INVESTIGATOR

WCCT Global

Locations

Research Site

Cypress, California, United States

Countries

United States

Other Identifiers

D5010C00004

Identifier Type: -

Identifier Source: org_study_id