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

NCT ID: NCT03420092

Last Updated: 2018-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-05
• Study Completion Date: 2018-04-18

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.

Detailed Description

This is a Randomized, 6-period, 6-treatment, Single-dose, Open-label, Single-center, Crossover, phase I Study to Assess the Relative Bioavailability of Different Formulations of AZD5718 and the Food Effect on the Selected Formulation of AZD5718 in Healthy Volunteers. 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. The optimal pharmacokinetic (PK) profile of AZD5718 is currently not known but working hypothesis is that a flatter PK profile will deliver the same efficacy at a lower dose/exposure compared to a fluctuating AZD5718 profile. Thus, formulations with different release rates will be evaluated. Potential food effect of a selected formulation would be determined in order to provide appropriate dose and dosing instructions for further development of AZD5718. This study would consist of 2 parts. In Part 1, 5 different formulations of AZD5718 would be provided to the participants 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. Part 1 of the study will be an open-label, randomized, 5-period, 5-treatment, single dose crossover study in 14 healthy participants (males and females of non-childbearing potential), performed at a single study center to ensure that at least 10 participants are evaluable. Each participant would be randomized to 1 of 10 treatment sequence according to a Williams design to receive the 5 treatments as following: Form 1 of AZD5718 tablets, Treatment B: Form 2 of AZD5718 tablets, Treatment C: Form 3 of AZD5718 tablets, Treatment D: Form 4 of AZD5718 tablets, and Treatment E: Form 5 of AZD5718 tablets. Participants will receive 1 treatment per treatment period. During each treatment period, participants would be dosed following an overnight fast of at least 10 hours. No fluids will be allowed apart from water which can be given until 2 hours before administration of the investigational medicinal product (IMP) and then from 1 hours after administration of the IMP. The dose would be administered with 240 mL of water. A standard meal would be given 4 hours after administration of the IMP. Participants should not lie fully supine (unless specified for certain assessments) for 4 hours after dosing. After completion the PK evaluation in Part 1, the formulation for Part 2 would be selected. At least 10 participants from Part 1 will be included in Part 2, to ensure that at least 8 participants are evaluable. For each participant included in Part 2, there would be minimum period of at least 2 weeks between the last dose of IMP in Part 1 and the dose of IMP in Part 2. During the treatment period in Part 2, participants would be dosed with the selected formulation of IMP with food. Participants would fast at least 10 hours prior to receiving the test meal. Participants should start the recommended meal 30 minutes prior to administration of the IMP. Participants would be required to consume the meal in 25 minutes; however, the IMP should be administered 30 minutes after start of the meal with 240 mL of water. No fluids would be allowed apart from water which can be given until 1 hour before administration of the IMP and then from 2 hours after administration of the IMP. Each participant will be involved in the study for approximately 5 to 6 weeks.

Conditions

Coronary Artery Disease

Study Design

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

Study Groups

Treatment A

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

Group Type: EXPERIMENTAL

Form 1 of AZD5718 tablets

Intervention Type: DRUG

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

Treatment B

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

Group Type: EXPERIMENTAL

Form 2 of AZD5718 tablets

Intervention Type: DRUG

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

Treatment C

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

Group Type: EXPERIMENTAL

Form 3 of AZD5718 tablets

Intervention Type: DRUG

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

Treatment D

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

Group Type: EXPERIMENTAL

Form 4 of AZD5718 tablets

Intervention Type: DRUG

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

Treatment E

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

Group Type: EXPERIMENTAL

Form 5 of AZD5718 tablets

Intervention Type: DRUG

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

Treatment F

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

Group Type: EXPERIMENTAL

Selected form (Form 2 - 5) of AZD5718 tablets

Intervention Type: DRUG

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

Interventions

Form 1 of AZD5718 tablets

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

Intervention Type: DRUG

Form 2 of AZD5718 tablets

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

Intervention Type: DRUG

Form 3 of AZD5718 tablets

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

Intervention Type: DRUG

Form 4 of AZD5718 tablets

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

Intervention Type: DRUG

Form 5 of AZD5718 tablets

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

Intervention Type: DRUG

Selected form (Form 2 - 5) of AZD5718 tablets

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated, written informed consent before any study specific procedures.

2. Healthy male and/or female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.

3. 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.

3.2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

4. 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.

5. 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.

Exclusion Criteria

1. 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.

2. 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.

3. Participants with any special dietary restrictions such as subjects that are lactose intolerant or are vegetarians/vegans.

4. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.

5. 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.

6. Any clinically significant abnormal findings in vital signs at screening, as judged by the PI.

7. Any clinically significant abnormalities on 12-lead ECG at screening and/or admission to the study unit, as judged by the PI.

8. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

9. Known of suspected Gilbert's syndrome and known or suspected history of drug abuse, as judged by the PI.

10. Has received another new chemical or biological entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest.

Note: Participants consented and screened, but not randomized in this study or a previous phase I study, are not excluded.

11. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months before screening.

12. 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.

13. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months before screening.

14. 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.

15. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks before the first administration of IMP.

16. 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 before the first administration of IMP or longer if the medication has a long half life.

17. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI.

18. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.

19. Subjects who have previously received AZD5718.

20. Judgment by the PI that the subject should not participate in the study if they have any ongoing or recent minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.

21. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship.

22. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.

• 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

Pablo Forte Soto, MD

Role: PRINCIPAL_INVESTIGATOR

PAREXEL Early Phase Clinical Unit London

Locations

Research Site

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

D7550C00005

Identifier Type: -

Identifier Source: org_study_id