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 (AZD3293DDI)

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers; Pharmacologic Action

Treatments: Drug: Group 3 AZD3293; Drug: Group 1 Itraconazole; Drug: Group 1 AZD3293; Drug: Group 2 AZD3293; Drug: Group 2 Diltiazem; Drug: Group 3 Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT02010970

D5010C00004

Details and patient eligibility

About

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

Enrollment: 56 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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56 participants in 3 patient groups

Group 1 AZD3293-itraconazole

Experimental group

Description:

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.

Treatment:

Drug: Group 1 AZD3293

Drug: Group 1 Itraconazole

Group 2 AZD3293-diltiazem

Experimental group

Description:

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.

Treatment:

Drug: Group 2 Diltiazem

Drug: Group 2 AZD3293

Group 3 AZD3293-midazolam

Experimental group

Description:

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

Treatment:

Drug: Group 3 Midazolam

Drug: Group 3 AZD3293