A Study to Assess the Amount of Drug Levels in Blood and Safety of AZD5718 Formulations in Healthy Volunteers

NCT ID: NCT04210388

Last Updated: 2020-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-14
• Study Completion Date: 2020-03-09

Brief Summary

The study is a randomized, single-dose, open-label, combined 2x2 dose and 3x3 dose crossover design in fixed sequence. In this study, the relative bioavailability of different formulations of AZD5718 will be assessed in healthy volunteers in order to compare the exposure of Formulations A to D to the AZD5718 film-coated tablet formulation. The overall treatment period will start with a 2-period, 2-dose treatment crossover, followed by a 3-period, 3-dose treatment crossover.

Detailed Description

This study will be conducted at a single study center in Parexel Early Phase Clinical Unit London.

A total of 12 healthy male and female volunteers (of non-childbearing potential) will be randomized.

The study will comprise:

• A screening period of maximum 28 days
• Five treatment periods
• There will be a washout period of 3 to 6 days between dose administrations
• Follow-up visit, 5 to 7 days after last dose

Each volunteer will be involved in the study for between 7 and 9 weeks. The volunteers will be admitted to the Unit on the day before first dosing in Treatment Period 1 until at least 72 hours after last dosing in Treatment Period 5.

Conditions

Coronary Artery Disease (CAD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AZD5718 tablet, Treatment A

Volunteers will receive single doses of AZD5718 tablet, Formulation A under fasted conditions.

Group Type: EXPERIMENTAL

AZD5718 tablet, Formulation A

Intervention Type: DRUG

Volunteers will receive single doses of AZD5718 tablet, Formulation A under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

AZD5718 tablet, Treatment B

Volunteers will receive single doses of AZD5718 tablet, Formulation B under fasted conditions.

Group Type: EXPERIMENTAL

AZD5718 tablet, Formulation B

Intervention Type: DRUG

Volunteers will receive single doses of AZD5718 tablet, Formulation B under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

AZD5718 tablet, Treatment C

Volunteers will receive single doses of AZD5718 tablet, Formulation C under fasted conditions.

Group Type: EXPERIMENTAL

AZD5718 tablet, Formulation C

Intervention Type: DRUG

Volunteers will receive single doses of AZD5718 tablet, Formulation C under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

AZD5718 tablet, Treatment D

Volunteers will receive single doses of AZD5718 tablet, Formulation C under fasted conditions.

Group Type: EXPERIMENTAL

AZD5718 tablet, Formulation D

Intervention Type: DRUG

Volunteers will receive single doses of AZD5718 tablet, Formulation D under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

AZD5718 film-coated tablet

Volunteers will receive single doses of AZD5718 film-coated tablet, Reference treatment under fasted conditions.

Group Type: ACTIVE_COMPARATOR

AZD5718 film-coated tablet, Reference treatment

Intervention Type: DRUG

Volunteers will receive single doses of AZD5718 film-coated tablet, Reference treatment under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

Interventions

AZD5718 tablet, Formulation A

Volunteers will receive single doses of AZD5718 tablet, Formulation A under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

Intervention Type: DRUG

AZD5718 tablet, Formulation B

Volunteers will receive single doses of AZD5718 tablet, Formulation B under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

Intervention Type: DRUG

AZD5718 tablet, Formulation C

Volunteers will receive single doses of AZD5718 tablet, Formulation C under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

Intervention Type: DRUG

AZD5718 tablet, Formulation D

Volunteers will receive single doses of AZD5718 tablet, Formulation D under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

Intervention Type: DRUG

AZD5718 film-coated tablet, Reference treatment

Volunteers will receive single doses of AZD5718 film-coated tablet, Reference treatment under fasted conditions. The dose will be administered with 240 mL (8 fluid ounces) of non-carbonated water after an overnight fast of at least 10 hours.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

For inclusion in the study volunteers should fulfill the following criteria:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male or female volunteers aged 18 to 55 years (inclusive at screening) with suitable veins for cannulation or repeated venipuncture.
• Males must be willing to use appropriate contraception methods.
• Females must have a negative pregnancy test at screening and on admission to the Clinical Unit (Day -1), must not be lactating and must be of non childbearing potential, confirmed at screening by fulfilling the criteria.
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, 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, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first dosing.
• Any clinically significant abnormalities in hematology, clinical chemistry, or urinalysis results, at screening or on admission to the Clinical Unit (Day -1), as judged by the Investigator, including:

1. Alanine aminotransferase (ALT) >1.5 x upper limit of normal (ULN).

2. Aspartate aminotransferase (AST) >1.5 x ULN.

3. Total bilirubin (TBL) >1.5 x ULN.

4. Gamma glutamyl transpeptidase (GGT) >1.5 x ULN. Out-of-range test may be repeated once for each visit at the discretion of the Investigator.

• Known or suspected Gilbert's syndrome.
• Any clinically significant abnormal findings in vital signs at screening or on admission to the Clinical Unit, as judged by the Investigator.
• Any clinically significant abnormalities on 12-lead ECG at screening, as judged by the Investigator.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Known or suspected history of drug abuse, as judged by the Investigator.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of first dosing in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.
• 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 Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5718.
• Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to screening.
• Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate) as judged by the Investigator.
• Positive screen for drugs of abuse or cotinine at screening or admission to the Clinical Unit or positive screen for alcohol on admission to the Clinical Unit.
• Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to first dosing.
• Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to first dosing or longer if the medication has a long half-life.
• Known or suspected history of alcohol or excessive alcohol intake, as judged by the Investigator.
• Involvement of any AstraZeneca, Parexel or study site employee or their close relatives.
• Volunteers who have previously received AZD5718.
• Judgement by the Investigator that the volunteers should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.
• Vulnerable volunteers, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

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

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr Pablo Forte Soto

Role: PRINCIPAL_INVESTIGATOR

Senior Clinical Research Physician, Parexel Early Phase Clinical Unit London

Locations

Research Site

Harrow, , United Kingdom

Countries

United Kingdom

Other Identifiers

D7550C00008

Identifier Type: -

Identifier Source: org_study_id