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

Coronary Artery Disease (CAD) Clinical Trial

Official title:

A Randomized, Single-dose, Open-label, Single-center, Crossover Study to Assess the Relative Bioavailability and Safety of Different Formulations of AZD5718 in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04210388
• Other study ID #: D7550C00008
• Status: Completed
• Phase: Phase 1
• Start date: January 14, 2020
• Est. completion date: March 9, 2020

Study information

• Verified date: March 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 9, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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:

Volunteers will not enter the study if any of the following exclusion criteria are fulfilled:

• 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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Artery Disease (CAD)

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United Kingdom	Research Site	Harrow

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve from zero to infinity (AUC)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Maximum observed plasma concentration (Cmax)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Drug concentration at 24 hours after dosing (C24)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Time to reach maximum observed plasma concentration (tmax)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Half-life associated with terminal slope (?z) of a semi-logarithmic concentration-time curve (t1/2?z)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Terminal elimination rate constant (?z)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Apparent total body clearance of drug from plasma after extravascular administration (CL/F)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Dose normalized AUC (AUC/D)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Dose normalized AUClast (AUClast/D)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Dose normalized Cmax (Cmax/D)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Primary	Dose normalized C24 (C24/D)	To evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation used in the ongoing Phase 2a clinical study (Reference treatment), in healthy volunteers	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post-dose
Secondary	Number of volunteers with having adverse events and/or abnormal findings in vital signs and/or clinical laboratory assessments and/or physical examination and/or electrocardiogram (ECG) evaluation and/or body weight	To further assess the safety and tolerability of single doses of AZD5718 in healthy volunteers	From Screening up to 9 weeks