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

NCT04210388 | Completed Phase 1 DMC

• 1 other identifier: D7550C00008
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease (CAD)

Keywords

Relative Bioavailability; Crossover Study; Safety

Outcome Measures

Primary Outcomes (13)

• 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

• 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

• 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

• 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

• 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

• Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz)

  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

• Terminal elimination rate constant (λz)

  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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (1)

• 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

  From Screening up to 9 weeks

Study Arms (5)

AZD5718 tablet, Treatment A

EXPERIMENTAL

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

Drug: AZD5718 tablet, Formulation A

AZD5718 tablet, Treatment B

EXPERIMENTAL

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

Drug: AZD5718 tablet, Formulation B

AZD5718 tablet, Treatment C

EXPERIMENTAL

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

Drug: AZD5718 tablet, Formulation C

AZD5718 tablet, Treatment D

EXPERIMENTAL

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

Drug: AZD5718 tablet, Formulation D

AZD5718 film-coated tablet

ACTIVE COMPARATOR

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

Drug: AZD5718 film-coated tablet, Reference treatment

Interventions

AZD5718 tablet, Formulation A 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 A

AZD5718 tablet, Formulation B 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 B

AZD5718 tablet, Formulation C 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 C

AZD5718 tablet, Formulation D 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 tablet, Treatment D

AZD5718 film-coated tablet, Reference treatment 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.

AZD5718 film-coated tablet

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 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.

You may not qualify if:

• 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:
• Alanine aminotransferase (ALT) \>1.5 x upper limit of normal (ULN).
• Aspartate aminotransferase (AST) \>1.5 x ULN.
• Total bilirubin (TBL) \>1.5 x ULN.
• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

AZD5718

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Dr Pablo Forte Soto

  Senior Clinical Research Physician, Parexel Early Phase Clinical Unit London

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: The overall treatment period will start with a 2-period, 2-dose treatment crossover, followed by a 3-period, 3-dose treatment crossover. The following treatments will be given: Treatment A: AZD5718 (Formulation A) Treatment B: AZD5718 (Formulation B) Treatment C: AZD5718 (Formulation C) Treatment D: AZD5718 (Formulation D) AZD5718 (AZD5718 film-coated tablet, Reference treatment)

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: December 24, 2019
• Study Start: January 14, 2020
• Primary Completion: March 9, 2020
• Study Completion: March 9, 2020
• Last Updated: March 25, 2020

Record last verified: 2020-03

Locations

GB (1)