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

Healthy Volunteers Clinical Trial

— AZD3293DDI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02010970
• Other study ID #: D5010C00004
• Status: Completed
• Phase: Phase 1
• First received: December 10, 2013
• Last updated: April 25, 2014
• Start date: December 2013
• Est. completion date: February 2014

Study information

• Verified date: April 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Volunteers
• Pharmacologic Action

Intervention

Drug:
• Group 1 AZD3293
AZD3293 oral solution
• Group 2 AZD3293
AZD3293 oral solution
• Group 3 AZD3293
AZD3293 oral solution
• Group 1 Itraconazole
itraconazole capsule
• Group 2 Diltiazem
Diltiazem ER tablet
• Group 3 Midazolam
midazolam syrup

Locations

Country	Name	City	State
United States	Research Site	Cypress	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	In Group 1, serial blood samples for AZD3293 plasma concentrations will be collected from predose to 96 hours after administration of AZD3293 on Day 1 and from predose to 144 hours after study drug administration on Day 8. Sparse blood samples for itraconazole plasma concentrations will be collected at predose (prior to administration of AZD3293) on Day 1 and 2 hours after the morning dose of itraconazole on Day 5 through Day 13. In Group 2, serial blood samples for AZD3293 plasma concentrations will be collected from predose to 96 hours after administration of AZD3293 on Day 1 and from predose to 144 hours after study drug administration on Day 8. Sparse blood samples for diltiazem plasma concentrations will be collected at predose (prior to administration of AZD3293) on Day 1 and 3 hours after diltiazem administration on Day 5 through Day 13.	up to day 13	No
Primary	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	Serial blood samples for midazolam plasma concentrations will be collected from predose to 24 hours after administration of midazolam on Day 1 and Day 17 and for 48 hours after administration of midazolam on Day 8. Sparse blood samples for AZD3293 plasma concentrations will be collected at predose (prior to administration of midazolam) on Day 1 and 2 hours after AZD3293 administration on Day 2 through Day 10.	up to day 17	No
Secondary	Safety profile in terms of Adverse events assessment		from Baseline and up to day 18	Yes
Secondary	Safety and tolerability in terms of lab tests assessment (hematology, chemistry, urinalysis)		from Baseline and up to day 18	Yes
Secondary	Safety and tolerability in terms of vital signs assessment (blood pressure, pulse and body temperature) and physical exams		from baseline and up till day 18	Yes
Secondary	Safety and tolerability by assessing changes in electrocardiogram (ECG) parameters		from Baseline and up to day 18	Yes
Secondary	Safety and tolerability by assessing telemetry records		from baseline and up to day 13	Yes
Secondary	Suicidality mesured by Columbia-Suicide Severity Rating Scale (C-SSRS)		from Baseline and up till day 18	Yes