A Study to Assess the Effect of Fluvoxamine and Smoking on Pharmacokinetics ( the Movement of Drugs Within the Body) of AZD4635 in Healthy Volunteers

NCT04478513 | Completed Phase 1

• 1 other identifier: D8730C00007
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase I, open-label, non-randomized, 2-period, fixed-sequence study in healthy volunteers who are either smokers or non-smokers, performed at a single Clinical Unit.

Conditions

Healthy Volunteer/DDI Study

Keywords

CYP1A2 Inhibitor; CYP1A2 Inducer; Pharmacokinetics; Adenosine 2A receptor (A2AR) antagonist

Outcome Measures

Primary Outcomes (3)

• Area under the plasma concentration-time curve from time zero to infinity (AUC)

  To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers

  Days 1-6 and Days 11-16

• Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)

  To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers

  Days 1-6 and Days 11-16

• Maximum observed plasma concentration (Cmax)

  To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers

  Days 1-6 and Days 11-16

Secondary Outcomes (1)

• Number of subjects with adverse events, serious adverse events and deaths

  From Screening upto Day 24

Study Arms (2)

Smokers

EXPERIMENTAL

Pre-specified group of participants.

Drug: AZD4635; Drug: Fluvoxamine

Non-smokers

EXPERIMENTAL

Pre-specified group of participants.

Drug: AZD4635; Drug: Fluvoxamine

Interventions

AZD4635 DRUG

During each treatment period subjects will receive a single dose of AZD4635 under fasting conditions.

Non-smokers; Smokers

Fluvoxamine DRUG

Daily oral single doses of fluvoxamine are planned to be administered to healthy volunteers in Treatment Period 2.

Non-smokers; Smokers

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male and female subjects of non-childbearing potential subjects aged 18 - 55 years (inclusive at screening) with suitable veins for cannulation or repeated venipuncture.
• Have a body mass index (BMI) between 18.5 and 32.0 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg, inclusive.
• Willingness and ability to comply with study and follow-up procedures.
• Subjects who are recruited as non-smokers should have no history of smoking cigarettes for \>6 months and test negative for urine cotinine levels at screening and admission.
• Subjects who are recruited as smokers must have a history of smoking \>10 cigarettes/day for \>6 months and have urine cotinine levels over 500 ng/ml at screening and admission.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the principal investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• History of cardiac disease; concurrent electroconvulsive therapy, diabetes mellitus, epilepsy, bleeding disorders (especially GI bleeding), mania and susceptibility to angle-closure glaucoma.
• Presence of refractory nausea and vomiting or chronic GI diseases.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the PI (based on laboratory parameters).
• Any clinically significant abnormal findings in vital signs at screening as judged by the PI.
• Systolic blood pressure (BP) \>140 and/or diastolic BP \> 90 mmHg, or history of hypertension at screening.
• Any confirmed clinically significant abnormalities on 12-lead ECG at screening, as judged by the PI.
• Haemoglobin A1c (HbA1c) \>5.7% at the screening visit.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibodies.
• Known or suspected history of drug abuse, within the past 2 years, as judged by the PI.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study.
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Interventions

Fluvoxamine

Intervention Hierarchy (Ancestors)

Oximes; Hydroxylamines; Amines; Organic Chemicals

Study Officials

• Pablo Forte Soto, Dr.

  Parexel Early Phase Clinical Unit London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is two-period, fixed sequence study in healthy volunteers who are either smokers or non-smokers. Twenty-eight subjects are planned to be enrolled; 14 subjects who are smokers and 14 subjects who are non-smokers. Enrolling 28 subjects will ensure that at least 12 subjects each from the smoking and the non-smoking populations are evaluated in this study.

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 20, 2020
• Study Start: July 21, 2020
• Primary Completion: December 23, 2020
• Study Completion: December 23, 2020
• Last Updated: January 6, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

GB (1)