A Study to Assess the Bioavailability of Different Formulations of AZD5718 and the Food Effect on the Selected Formulation of AZD5718 in Healthy Volunteers

NCT03420092 | Completed Phase 1 DMC

• 1 other identifier: D7550C00005
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the relative bioavailability of different formulations of AZD5718 will be determined in order to compare it with the formulation used in a previous Phase 2a study and confirm appropriate drug exposure. This study consist of 2 parts. In Part 1, 5 different formulations of AZD5718 would be provided to the participant in fasting condition in a randomized order. After evaluation of Part 1 a single formulation would be selected for dosing in fed condition in Part 2. Each participant will be involved in the study for approximately 5 to 6 weeks. Fourteen participants will be randomized to ensure at least 10 evaluable participants at the end of the last treatment period.

Conditions

Coronary Artery Disease

Keywords

vasoactive leukotrienes by leukocytes; bioavailability

Outcome Measures

Primary Outcomes (4)

• Area under plasma concentration-time curve (AUC) of AZD5718

  To assess the pharmacokinetics (PK) parameter AUC to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.

  At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.

• AUC from time zero to time of last quantifiable concentration (AUC[0-t]) of AZD5718

  To assess the PK parameter AUC(0-t)to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.

  At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.

• Observed maximum plasma concentration (Cmax) of AZD5718

  To assess the PK parameter Cmax to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.

  At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.

• Observed plasma concentration at 24 hours post dose (C24) of AZD5718

  To assess the PK parameter C24 to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.

  24 hour post dose

Secondary Outcomes (49)

• Cmax of AZD5718 in fed and fasted conditions

  At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.

• C24 of AZD5718 in fed and fasted conditions

  At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.

• AUC(0-t) of AZD5718 in fed and fasted conditions

  At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.

• AUC of AZD5718 in fed and fasted conditions

  At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.

• Number of participants with adverse events

  From randomization throughout the treatment period (Day 1 to 3) and follow-up Visit (Day 5 to 7) assessed maximum upto 6 weeks.

Study Arms (6)

Treatment A

EXPERIMENTAL

The participant will be administered with Form 1 of AZD5718 tablets with an overnight fast of at least 10 hours.

Drug: Form 1 of AZD5718 tablets

Treatment B

EXPERIMENTAL

The participant will be administered with Form 2 of AZD5718 tablets with an overnight fast of at least 10 hours.

Drug: Form 2 of AZD5718 tablets

Treatment C

EXPERIMENTAL

The participant will be administered with Form 3 of AZD5718 tablets with an overnight fast of at least 10 hours.

Drug: Form 3 of AZD5718 tablets

Treatment D

EXPERIMENTAL

The participant will be administered with Form 4 of AZD5718 tablets with an overnight fast of at least 10 hours.

Drug: Form 4 of AZD5718 tablets

Treatment E

EXPERIMENTAL

The participant will be administered with Form 5 of AZD5718 tablets with an overnight fast of at least 10 hours.

Drug: Form 5 of AZD5718 tablets

Treatment F

EXPERIMENTAL

The participant will be administered with selected form (one of Form 2-5) of AZD5718 tablets 30 minutes after start of the meal.

Drug: Selected form (Form 2 - 5) of AZD5718 tablets

Interventions

Form 1 of AZD5718 tablets DRUG

The participants will be dosed with Form 1 of AZD5718 following an overnight fast of at least 10 hours.

Treatment A

Form 2 of AZD5718 tablets DRUG

The participants will be dosed with Form 2 of AZD5718 following an overnight fast of at least 10 hours.

Treatment B

Form 3 of AZD5718 tablets DRUG

The participants will be dosed with Form 3 of AZD5718 following an overnight fast of at least 10 hours.

Treatment C

Form 4 of AZD5718 tablets DRUG

The participants will be dosed with Form 4 of AZD5718 following an overnight fast of at least 10 hours.

Treatment D

Form 5 of AZD5718 tablets DRUG

The participants will be dosed with Form 5 of AZD5718 following an overnight fast of at least 10 hours.

Treatment E

Selected form (Form 2 - 5) of AZD5718 tablets DRUG

The participant will be administered with selected form (one of Form 2-5) of AZD5718 tablets 30 minutes after start of the meal.

Treatment F

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 before any study specific procedures.
• Healthy male and/or female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non childbearing potential, confirmed at screening by fulfilling one of the following criteria 3.1. Postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels in the postmenopausal range.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• 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.
• Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the 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.
• Participants with any special dietary restrictions such as subjects that are lactose intolerant or are vegetarians/vegans.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis results, at screening and/or admission to the study unit as judged by the PI.
• Any clinically significant abnormal findings in vital signs at screening, as judged by the PI.
• Any clinically significant abnormalities on 12-lead ECG at screening and/or admission to the study unit, as judged by the PI.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Known of suspected Gilbert's syndrome and known or suspected history of drug abuse, as judged by the PI.
• Note: Participants consented and screened, but not randomized in this study or a previous phase I study, are not excluded.
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months before screening.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI 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 before screening.
• Positive screen for drugs of abuse or cotinine (screening only) at screening or on each admission to the study center or positive screen for alcohol on each admission to the study center.
• Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks before the first administration of IMP.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

London, 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

• Pablo Forte Soto, MD

  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

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: February 5, 2018
• Study Start: February 5, 2018
• Primary Completion: April 18, 2018
• Study Completion: April 18, 2018
• Last Updated: April 23, 2018

Record last verified: 2018-04

Locations

GB (1)